Biomedical subjects

K Kawabata

Publications and source records attributed to K Kawabata.

At least 127 records · Page 7Linked to original sources

PubMed1997

P3 latency change in aging and Parkinson disease.

OBJECTIVE: To evaluate whether age-related slowing of mental processing assessed by event-related potentials is more prominent in patients with Parkinson disease (PD) than in age-matched control subjects. DESIGN: Consecutive case series of patients with PD and an age-matched control group. SETTING: A university hospital in Nishinomiya, Japan. STUDY PARTICIPANTS: Twenty-eight nondemented patients with PD and 28 age-matched control subjects. MAIN OUTCOME MEASURES: The P3 component of the event-related potentials was elicited during a visual semantic discrimination task. The relation of the P3 latency and the reaction time (RT) to age within each group was evaluated using correlation and regression analysis. The relationship among the P3 latency, the RT, and age was also assessed by dividing both groups into younger (age < 60 years) and older (age > or = 60 years) subgroups. RESULTS: The P3 latency and the RT of patients with PD were significantly longer than those of the control subjects (P < .01 and P < .02, respectively). There was a significant correlation between the P3 latency and age in both the parkinsonian and control groups (P < .01 and P < .05, respectively). The slope (b = 3.54 ms/y) of the P3 latency vs age was steeper among the patients with PD than among the control subjects (b = 1.66 ms/y) at the Pz site. The P3 latency in the older parkinsonian group (n = 16) was significantly prolonged compared with that in the older control group (n = 16) (P < .01), while no difference was found between the younger patients (n = 12) and the younger control group (n = 12). Similar trends were found for the RTs (P < .05). Neither the P3 latency nor the RT was correlated with any variable (eg, medication, mental status, illness duration, or motor disability). CONCLUSION: The results provide evidence that patients with PD experience excessive cognitive slowing with advancing age.

Adult↗

PubMed1997

Partial laryngectomy in the treatment of radiation-failure of early glottic carcinoma.

BACKGROUND: This study was undertaken to analyze the functional results, complications, local control rates, and survival in patients undergoing conservation surgery for squamous cell carcinoma (SCC) of the larynx as a salvage procedure for recurrent tumors after previous radiotherapy. METHODS: Twenty-one patients underwent frontolateral laryngectomy for radiation failure, T1 and T2 glottic SCC, at the Cancer Institute Hospital, Tokyo, from 1976 to 1991. All patients were men between the ages of 42 and 83 years. The disease-free interval ranged from 1 to 87 months (median, 26 months). The stage at initial treatment was T1 in 17 patients and T2 in four patients. Local recurrence developed in three patients. RESULTS: The rate of local control was influenced by a surgical margin of less than 1 mm (p < 0.05). Overall voice preservation was achieved in 86% of the patients. The 5-year and 10-year survival rates following frontolateral laryngectomy were 86% and 70%, respectively. Maximum phonation time after surgery ranged from 4 to 18 seconds (median, 8.1 seconds). CONCLUSIONS: These results indicate that in carefully selected cases, frontolateral laryngectomy may be used for treating radiation failure stage I or II vocal cord carcinomas with good success. Careful follow-up may be necessary in patients with a close surgical margin.

Adult↗

PubMed1997

Expression of bcl-2, bax, and bcl-XL proteins in azoxymethane-induced rat colonic adenocarcinomas.

Using western blotting and immunochemical analysis, we investigated alterations in the expression of the apoptosis-related proteins bcl-2, bax, and bcl-X in colonic adenocarcinomas induced by subcutaneous injection of azoxymethane (AOM) (15 mg/kg body weight weekly for 2 wk) into male Sprague-Dawley rats. Expression of the apoptosis-repressor bcl-2 in the colonic tumors was significantly weaker (0.6-fold) than that in adjacent non-neoplastic mucosa. The expression of bax protein, an apoptosis accelerator, was significantly stronger (7.33-fold) in all the tumors than in the non-tumoral mucosa. bcl-XL protein, which functions as a repressor of apoptosis, was significantly upregulated (3.23-fold) in all the tumors when compared with the non-neoplastic mucosa. There was no significant difference between the expression of these proteins in the non-neoplastic mucosa of the AOM-treated rats and in the normal mucosa of saline-treated control rats. As determined by immunohistochemical analysis, the tumor cells had more bax and bcl-X protein. These findings indicate that the regulation of the apoptosis-related proteins bcl-2, bax, and bcl-XL was altered in the AOM-induced colonic neoplastic tissue. In terms of resistance to apoptosis, elevated levels bcl-XL protein may have considerable meaning in this experimental model as well as in human colorectal cancer.

Adenocarcinoma↗

PubMed1997

Improvement of diagnostic accuracy of transvaginal ultrasound for identification of endometrial malignancies by using cutoff level of endometrial thickness based on length of time since menopause.

Transvaginal ultrasonography (TVS) is considered useful for identifying endometrial malignancies, but it has a low specificity and a high false-positive rate. The purpose of this study was to improve the specificity of this technique. A total of 300 postmenopausal women were studied. They were clinically evaluated by TVS and endometrial histology. Twenty women yielded pathologic findings on endometrial examination. The mean endometrial thickness was related to the length of time since menopause. For endometria with pathological findings, sonographic measurements of endometria with a thickness of greater than 3 mm exhibited 95.0% sensitivity, 68.5% specificity, 19.4% positive predictive value, and 99.4% negative predictive value. If a 4-mm cutoff limit was used for < 5 years since menopause and a 3-mm cutoff limit was used for > or = 5 years since menopause, 95.0% sensitivity, 78.1% specificity, 25.7% positive predictive value, and 99.5% negative predictive value were obtained. The specificity and false-positive rate were improved when the cutoff limit was decided based on the length of time since menopause. The cutoff level of the endometrial thickness for detection of endometrial malignancies should be decided based on the length of time since menopause.

Age Factors↗

PubMed1997

Studies on 3'-quaternary ammonium cephalosporins--III. Synthesis and antibacterial activity of 3'-(3-aminopyrazolium) cephalosporins.

The synthesis and in vitro antibacterial activity of 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]cephalos porins bearing N-mono or dialkyl and carbamoyl aminopyrazolium, and five- or six-membered rings fused to the 3-aminopyrazolium methyl groups at the 3-position, are described. Aminopyrazolium methyl cephalosporins (23e, f, i), with fused saturated and unsaturated rings were especially effective against Staphylococcus strains compared to 3-amino-2-methylpyrazolium methyl cephalosporin (1). Among the cephalosporins prepared in this work, 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]-3-(4,5, 6, 7-tetrahydro-1-pyrazolo[1,5-a]pyrimidinio)methyl-3-cephem-4-carbox ylate (23f) showed a good balance of antibacterial activity against both Gram-positive bacteria including Staphylococcus aureus and Gram-negative bacteria including P. aeruginosa. An imidazopyrazolium group at the 3-position in, for example, cephalosporin (23i) was particularly effective for improving antibacterial activity against MRSA.

Cephalosporins↗

PubMed1997

Studies on 3'-quaternary ammonium cephalosporins--IV. Synthesis and antibacterial activity of 3'-(2-alkyl-3-aminopyrazolium) cephalosporins related to FK037.

The synthesis and in vitro antibacterial activity of 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido] cephalosporins bearing various 2-alkyl-3-aminopyrazolium groups at the 3-position are described. Antibacterial activity against MRSA was affected by the nature of the substituent at the 2-position on the 3'-aminopyrazolium groups. Among the cephalosporins prepared in this study, 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]-3-[3-am ino-2-(2 -hydroxyethyl)-pyrazolio]methyl-3-cephem-4-carboxylate sulfate (23e, FK037) showed extremely potent broad-spectrum activity against both Gram-positive bacteria including MRSA, and Gram-negative bacteria including Pseudomonas aeruginosa. In particular, the in vivo activity against MRSA of FK037 was the highest of all the beta-lactam antibiotics tested.

Anti-Bacterial Agents↗

PubMed1997

Non-polarized secretion of mouse interferon-beta from gene-transferred human intestinal Caco-2 cells.

PURPOSE: The intestinal epithelium is considered to be a feasible target for somatic gene therapy. To this end, Caco-2 cells derived from human colon carcinoma were transfected with a mouse interferon-beta (IFN-beta) expression vector and several stable sublines were established; this hetero-specific cytokine allows unexpected cellular effects to be avoided. Using the highest mouse IFN-beta-producing sublines, the mode of IFN secretion was examined. METHODS: The secretion polarity of mouse IFN-beta in its gene-transduced Caco-2 sublines was studied in a bicameral culture system in which the chambers were separated by microporous filters. RESULTS: Mouse IFN-beta was secreted to the same extent from both apical and basolateral surfaces of the transduced cells regardless of cell aging. CONCLUSIONS: These results suggest that in the intestinal epithelium exogenous gene products such as IFNs can be delivered to both the luminal and blood sides in vivo. Thus, the intestinal epithelium may be suitable for systemic and local delivery of therapeutic proteins by gene transfer.

Animals↗

PubMed1997

Citrus auraptene inhibits chemically induced colonic aberrant crypt foci in male F344 rats.

The modifying effect of dietary administration of auraptene isolated from the peel of citrus fruit (Citrus natsudaidai Hayata) on the development of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) was investigated in rats. Male F344 rats were given s.c. injections of AOM (15 mg/kg body wt) once a week for 3 weeks to induce ACF. They also received diets containing 100 or 500 p.p.m. auraptene for 5 weeks, starting 1 week before the first dose of AOM. At termination of the study (week 5) dietary administration of auraptene caused a significant reduction in the frequency of ACF in a dose-dependent manner (P < 0.05). Feeding of auraptene suppressed expression of cell proliferation biomarkers (5-bromo-2'-deoxyuridine labeling-index, ornithine decarboxylase activity, polyamine content and number of silver stained nucleolar organizer region protein particles) in the colonic mucosa and the occurrence of micronuclei caused by AOM. Also, auraptene increased the activities of phase II enzymes (glutathione S-transferase and quinone reductase) in the liver and colon. These findings might suggest that inhibition of AOM-induced ACF may be associated, in part, with increased activity of phase II enzymes in the liver and colon and suppression of cell proliferation in the colonic mucosa.

Animals↗

PubMed1997

Modulation of N-methyl-N-amylnitrosamine-induced rat oesophageal tumourigenesis by dietary feeding of diosmin and hesperidin, both alone and in combination.

The modifying effects of flavonoids diosmin and hesperidin during the initiation and post-initiation phases of oesophageal carcinogenesis initiated with N-methyl-N-amylnitrosamine (MNAN) were investigated in male Wistar rats. At 7 weeks of age, all animals except those treated each test chemical alone and control groups were given weekly intraperitoneal injections of MNAN (12.5 mg/kg body weight/injection) for 12 weeks to induce oesophageal neoplasms. For examining the modifying effects of 'initiation' treatment of test compounds, groups of animals were fed the diets containing 1000 ppm diosmin and 1000 ppm hesperidin, and the diet containing both compounds (900 ppm diosmin and 100 ppm hesperidin) for 13 weeks, starting 7 days before the MNAN dosing and then switched to the basal diet. For examining the modifying effects of 'post-initiation' treatment of these compounds, the groups given MNAN and a basal diet were switched to the experimental diets containing diosmin, hesperidin or diosmin combined with hesperidin at 1 week after the stop of MNAN injection, and maintained on these diets for 7 weeks. The other groups consisted of rats given test compounds alone or untreated rats. All animals were necropsied at the termination of the study (week 20) to determine the incidences of oesophageal neoplasms and preneoplasms, blood polyamine levels, and cell proliferation activity estimated by 5-bromodeoxyuridine (BrdU)-labelling index and by morphometric analysis of silver-stained nucleolar organizer regions' protein (AgNORs). A number of oesophageal neoplasms developed in rats treated with MNAN alone (75% and 100% incidences of carcinoma and papilloma, respectively). 'Initiation' feeding of diosmin significantly decreased the incidence of squamous cell carcinoma (P < 0.05). Also, 'initiation feeding' of both compounds singly or in combination caused a significant reduction in the multiplicities of oesophageal carcinoma and papilloma (diosmin, 78 and 58% reduction; hesperidin, 70 and 50% reduction; and the combination regimen, 70 and 30% reduction, P < 0.005). 'Post-initiation' feeding slightly decreased the multiplicities of these oesophageal neoplasms. Also, these dietary regimens reduced the multiplicities of preneoplastic lesions (hyperplasia and severe dysplasia; P < 0.05). There were no pathological alterations in rats treated with both compounds alone or the combined regimen alone or those in an untreated control group. Similarly, feeding of these compounds significantly decreased the expression of cell proliferation biomarkers (BrdU-labelling index and AgNORs number) of the non-lesional oesophageal epithelium (P < 0.05). Blood polyamine concentrations were also lowered in rats given the carcinogen and test compounds, both alone and in combination, when compared with those of rats given MNAN alone (P < 0.05). These findings suggest that diosmin and hesperidin supplementation, individually or in combination, is effective in inhibiting the development of oesophageal cancer induced by MNAN when given during the initiation phase, and such inhibition might be related to suppression of increased cell proliferation caused by MNAN in the oesophageal mucosa.

Administration, Oral↗

PubMed1997

A xanthine oxidase inhibitor 1'-acetoxychavicol acetate inhibits azoxymethane-induced colonic aberrant crypt foci in rats.

The modifying effect of dietary administration of a xanthine oxidase inhibitor 1'-acetoxychavicol acetate (ACA) present in an edible plant Languas galanga in Thailand on the development of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) was investigated in rats. Male F344 rats were given s.c. injections of AOM (15 mg/kg body wt) once a week for 3 weeks to induce colonic ACF. They were fed the diets containing 100 or 200 ppm ACA for 5 weeks, starting 1 week before the first dosing of AOM. At the termination of the study (week 5), AOM induced 118 +/- 28 ACF/colon. Dietary administration of ACA caused significant reduction in the frequency of ACF (41% inhibition by 100 ppm ACA feeding and 37% inhibition by 200 ppm ACA feeding, P<0.01). Such inhibition might be associated with suppression of the proliferation biomarkers' expression such as ornithine decarboxylase activity in the colonic mucosa, number of silver-stained nucleolar organizer regions' protein in the colonic mucosal cell nuclei and blood polyamine content. These results indicate that ACA could inhibit the development of AOM-induced ACF through its suppression of cell proliferation in the colonic mucosa and ACA might be a possible chemopreventive agent against colon tumourigenesis.

Animals↗

PubMed1997

Chemoprevention of azoxymethane-induced rat colon carcinogenesis by the naturally occurring flavonoids, diosmin and hesperidin.

The modulating effects of dietary feeding of two flavonoids, diosmin and hesperidin, both alone and in combination, during the initiation and post-initiation phases on colon carcinogenesis initiated with azoxymethane (AOM), were investigated in male F344 rats. Animals were initiated with AOM by weekly s.c. injections of 15 mg/kg body wt for 3 weeks to induced colon neoplasms. Rats were fed the diets containing diosmin (1000 ppm), hesperidin (1000 ppm) or diosmin (900 ppm) + hesperidin (100 ppm) for 5 weeks (initiation treatment) or 28 weeks (post-initiation treatment). The others contained the groups of rats treated with diosmin, hesperidin alone or in combination, and untreated. At the end of the study (32 weeks), the incidence and multiplicity of neoplasms (adenoma and adenocarcinoma) in the large intestine of rats initiated with AOM together with, or followed by, a diet containing diosmin or hesperidin were significantly smaller than those of rats given AOM alone (P <0.001). The combination regimen during the initiation and post-initiation stages also inhibited the development of colonic neoplasms, but the tumor data did not indicate any beneficial effect of diosmin and hesperidin administered together as compared with when these agents were given individually. In addition, feeding of diosmin and hesperidin, both alone and in combination, significantly inhibited the development of aberrant crypt foci. As for cell proliferation biomarkers, dietary exposure of diosmin and hesperidin significantly decreased the 5'-bromodeoxyuridine-labeling index and argyrophilic nuclear organizer region's number in crypt cells, colonic mucosal ornithine decarboxylase activity, and polyamine levels in the blood. These results indicate that diosmin and hesperidin, both alone and in combination, act as a chemopreventive agent against colon carcinogenesis, and such effects may be partly due to suppression of cell proliferation in the colonic crypts, although precise mechanisms should be clarified.

Animals↗

PubMed1997

5-Fluorouracil + cisplatin + mitomycin C is a relatively most effective combination against xenograft lines of human colorectal cancer.

5-Fluorouracil (5-FU) has been an accepted effective against colorectal cancer, but combination regimens resulted in a lesser effect than 5-FU alone. The present study was designed to evaluate the efficiency of various combination chemotherapies, including 5-FU, on human colorectal cancer xenograft lines (CC-KK and RC-TK), which had been passed by transplantation in nude mice. Eight anticancer agents [5-FU, mitomycin C (MMC), adriamycin (ADR), 4'-epirubicin (EPIR), carboquone (CQ), cisplatin, carboplatin and etoposide (VP-16)] and their combinations were evaluated at 2-4 times the clinical dose. When the agents were administered singly, 5-FU, EPIR and CQ were effective against CC-KK, and 5-FU, MMC, EPIR, ADR, CQ and carboplatin were effective against RC-TK. Of the two-agent combinations including 5-FU, cisplatin + 5-FU was the most effective against both CC-KK and RC-TK. However, of the three-agent combinations, only cisplatin + 5-FU + MMC was more effective against both lines than cisplatin + 5-FU. These results suggest that cisplatin + 5-FU + MMC may be the most useful regimen against colorectal cancers in clinical application.

Adenocarcinoma↗

PubMed1997

Inhibitory effect of NS-398, a selective cyclooxygenase-2 inhibitor, on azoxymethane-induced aberrant crypt foci in colon carcinogenesis of F344 rats.

Prostaglandin E2, which is produced by cyclooxygenase (COX) during arachidonic acid metabolism, is considered to be related to colon carcinogenesis. Therefore, the effect of NS-398 (N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide), a COX-2 inhibitor, was examined in azoxymethane (AOM)-induced colon carcinogenesis in rats in this study. In the first experiment, groups 1-3 were treated with AOM (15 mg/kg, s.c.) 3 times at intervals of a week from 5 weeks of age. Groups 2 and 3 were respectively given 1 mg/kg and 10 mg/kg of NS-398 in 5% gum arabic aqueous solution 3 times per week by oral gavage during the experiment. Six weeks after the first exposure to AOM, aberrant crypt foci (ACF) were counted in the colonic mucosa of all rats. The mean occurrence of ACF per length in rats given 1 mg/kg b.w. or 10 mg/kg b.w. of NS-398 was reduced to 65.7% or 52.8%, respectively, of that in rats treated with only AOM. Levels of COX-2 mRNA expression in groups treated with AOM, regardless of NS-398, were slightly higher than that in the group treated with NS-398 alone as judged from reverse transcription-polymerase chain reaction analysis. In the second experiment, the effect of NS-398 at different times, i.e., during initiation and post-initiation, was examined. Treatment with NS-398 in both phases significantly inhibited the appearance of ACF. The results imply that NS-398 might have a chemopreventive potential.

Animals↗

PubMed1997

Regressive effects of various chemopreventive agents on azoxymethane-induced aberrant crypt foci in the rat colon.

Regressive effects of four chemopreventive agents [5-hydroxy-4-(2-phenyl-(E)-ethenyl)-2(5H)-furanone (KYN-54), S-methyl methanethiosulfonate (MMTS), chlorogenic acid (CA), and piroxicam] on azoxymethane (AOM)-induced aberrant crypt foci (ACF) in the colon of male F344 rats were examined by dietary exposure. At six weeks of age, 60 rats of groups 1 through 5 received subcutaneous injections of AOM (15 mg/kg body weight) once a weeks. Twelve weeks after the first carcinogen injection, when the occurrence of ACF was maximal, the rats in groups 2 through 5 were started on diet containing the test chemicals as follows: group 2, KYN-54 (0.02%); group 3, MMTS (0.01%); group 4, CA (0.025%); and group 5, piroxicam (0.0125%). Group 1 (20 rats) was kept on the basal diet alone, and group 6 (12 rats) served as an untreated control. Rats in each group were killed at 6, 12, 18, or 24 weeks after the start of the experiment, and the yield of ACF in the colon of each group at 18 or 24 weeks was compared with that at 12 weeks. The number of ACF per rat colon of each group at 18 or 24 weeks was smaller than that at 12 weeks. The reduction rates at 18 weeks were 7% in group 1 (AOM alone), 11% in group 2 (AOM + KYN-54), 10% in group 3 (AOM + MMTS), 51% in group 4 (AOM + CA) (P < 0.01), and 33% in group 5 (AOM + piroxicam) (P < 0.02), while at 24 weeks they were 12%, 26%, 51% (P < 0.002), 43% (P < 0.05), and 70% (P < 0.001), respectively. These results indicate that chemopreventive agents for large bowel carcinogenesis, i.e., KYN-54, MMTS, CA, and piroxicam, are not only able to prevent the development of ACF, but also can regress ACF, which are regarded as precursor lesions of colorectal cancer.

4-Butyrolactone↗

PubMed1997

Chemoprevention of azoxymethane-induced rat colon carcinogenesis by a xanthine oxidase inhibitor, 1'-acetoxychavicol acetate.

In our studies to find natural compounds with chemopreventive efficacy in foods, using azoxymethane (AOM)-induced colonic aberrant crypt foci and colonic mucosal cell proliferation as biomarkers, a xanthine oxidase inhibitor, 1'-acetoxychavicol acetate (ACA), present in the edible plant Languas galanga from Thailand was found to be effective. This study was conducted to test the ability of ACA to inhibit AOM-induced colon tumorigenesis when it was fed to rats during the initiation or post-initiation phase. Male F344 rats were given three weekly s.c. injections of AOM (15 mg/kg body weight) to induce colonic neoplasms. They were fed diet containing 100 or 500 ppm ACA for 4 weeks, starting one week before the first dosing of AOM (the initiation feeding). The other groups were fed the ACA diet for 34 weeks, starting one week after the last AOM injection (the post-initiation feeding). At the termination of the study (week 38), AOM had induced 71% incidence of colonic adenocarcinoma (12/17 rats). The initiation feeding with ACA caused significant reduction in the incidence of colon carcinoma (54% inhibition by 100 ppm ACA feeding and 77% inhibition by 500 ppm ACA feeding, P = 0.03 and P = 0.001, respectively). The post-initiation feeding with ACA also suppressed the incidence of colonic carcinoma (45% inhibition by 100 ppm ACA feeding and 93% inhibition by 500 ppm ACA feeding, P = 0.06 and P = 0.00003, respectively). Such inhibition was dose-dependent and was associated with suppression of proliferation biomarkers, such as ornithine decarboxylase activity in the colonic mucosa, and blood and colonic mucosal polyamine contents. ACA also elevated the activities of phase II enzymes, glutathione S-transferase (GST) and quinone reductase (QR), in the liver and colon. These results indicate that ACA could inhibit the development of AOM-induced colon tumorigenesis through its suppression of cell proliferation in the colonic mucosa and its induction of GST and QR. The results confirm our previous finding that ACA feeding effectively suppressed the development of colonic aberrant crypt foci. These findings suggest possible chemopreventive ability of ACA against colon tumorigenesis.

Animal Feed↗

PubMed1997

In vitro and in vivo enhancement of sonodynamically active cavitation by second-harmonic superimposition.

Acoustic cavitation, the primary mechanism of sonochemical effects, is known to be induced more easily by standing waves than by progressive waves. It has been found that acoustic cavitation can be an order of magnitude enhanced by superimposing the second harmonic on the fundamental. Significant synergistic effects between the fundamental and the second harmonic were observed in both in vitro and in vivo experiments employing a progressive wave field. Second-harmonic superimposition induces in vitro sonochemical reaction as well as fractional harmonic emission at a relatively low ultrasonic intensity even in a progressive wave field. The effect of second-harmonic superimposition was also investigated using exteriorized mouse livers suspended in degassed saline. The intensity threshold for the production of focal tissue damage, paired with fractional harmonic emission was significantly lowered by second-harmonic superimposition especially when a sonodynamically active agent had been administered to the mouse. Insonation with second-harmonic superimposition in combination with such administration may have potential use for selective tumor treatment.

Acoustics↗

PubMed1997

Oral immunization with PspA elicits protective humoral immunity against Streptococcus pneumoniae infection.

Streptococcus pneumoniae is a major respiratory mucosal pathogen affecting infants and children. Although a polysaccharide-based vaccine has been useful in adult populations, it does not elicit protective immunity in infants and young children. Pneumococcal surface protein A (PspA) is a highly immunogenic surface protein produced by all strains of Streptococcus pneumoniae. Previous studies have shown that systemic immunization of mice with PspA can elicit protective immunity against fatal pneumococcal infection. In this study, we demonstrated that oral immunization with PspA could elicit protective immune responses against pneumococcal infection. When mice were orally immunized with PspA alone, low levels of PspA-specific immunoglobulin G (IgG) responses were induced in serum; none was induced in secretion. On the other hand, when PspA was given orally with the mucosal adjuvant cholera toxin (CT), significant levels of IgG and IgA anti-PspA responses were induced in serum. The major IgG subclass was IgG1, followed by IgG2b, a profile of antibody response supported by Th2-type cells. In addition, all mice orally immunized with PspA and CT were protected from the lethal challenge with capsular serotype 3 S. pneumoniae A66. These results suggested that an oral PspA vaccine may be a useful means of preventing pneumococcal disease.

Adjuvants, Immunologic↗

PubMed1997

Effects of a specific cysteinyl leukotriene antagonist, pranlukast, on antigen-induced cysteinyl leukotriene-mediated rhinitis in guinea pigs.

To examine the effects of a specific cysteinyl leukotriene (cysLT) antagonist, pranlukast, on allergic rhinitis, antigen-induced rhinitis in guinea pigs was modified by pretreatment with an cyclooxygenase inhibitor (indomethacin) followed by an H1-blocker (pyrilamine). Intranasal ovalbumin (OVA) administration in actively sensitized guinea pigs resulted in concentration-dependent increases in nasal permeability and nasal airway resistance (NAR). Although pyrilamine (1 mg/kg, i.v.) abolished these antigen-induced changes, pretreatment with indomethacin (5 mg/kg, i.v.) followed by pyrilamine enhanced these responses to a degree similar to that observed with OVA challenge alone. Analyses of nasal perfusate in indomethacin/pyrilamine-pretreated animals showed that cysLTs increased by 270.8%, whereas thromboxane B2 decreased by 88.3% as compared with those on challenged with OVA alone. Oral administration of pranlukast (1-10 mg/kg) dose-dependently prevented increases in nasal permeability and NAR of indomethacin/pyrilamine-pretreated animals. However, an anti-allergic agent, azelastine, did not affect these responses. These results indicate that pranlukast suppresses antigen-induced cysLT-mediated responses of allergic rhinitis in actively sensitized guinea pigs. A cysLT antagonist, pranlukast, may thus prevent cysLT-mediated symptoms of allergic rhinitis.

Airway Resistance↗