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Biomedical subjects

M Takamoto

Publications and source records attributed to M Takamoto.

At least 37 records · Page 2Linked to original sources

Effects of monoclonal antibodies to adhesion molecules on eosinophilic myocarditis in Toxocara canis-infected CBA/J mice.

Eosinophilic myocarditis followed by fibrosis of the cardiac muscle was observed in addition to peripheral blood eosinophilia in CBA/J mice infected with Toxocara canis. The infected mice were used as an experimental model of eosinophilic endomyocarditis associated with hypereosinophilic syndrome. Effects of in vivo treatment with MoAbs to adhesion molecules on eosinophilic myocarditis were examined using this experimental model. Expressions of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on endothelial cells of capillaries in myocardium were increased 1 and 2 weeks after infection. Infiltration of very late antigen (VLA)-4+ and/or CD11a+ cells into the cardiac muscles was also observed 1 and 2 weeks after infection. Infiltration of eosinophils into the heart was significantly suppressed by anti-CD18 MoAb and anti-VLA-4 MoAb, and focal fibrosis of the cardiac muscle was also significantly suppressed by combined administration of anti-CD18 and anti-ICAM-1 MoAbs. These results indicate that adhesion molecules may play important roles in eosinophilic myocarditis, and that blockade of interaction between adhesion molecules and their ligands may help to control it.

Animals↗

Eosinophilia, IgE production, and cytokine production by lung T cells in surface CD4-deficient mutant mice infected with Toxocara canis.

Mutant mice deficient in CD4+ T cells and their normal and heterozygous littermates were infected with Toxocara canis, and compared for eosinophilia, total and Toxocara-specific immunoglobulin E (IgE) production, and in vitro cytokine production by lung cells. The numbers of eosinophils in the peripheral blood of normal and heterozygous mice peaked on days 10 and 21, although mutant mice showed eosinophilia with a peak on day 10. This indicates that the first peak on day 10 is CD4 independent and the second peak is CD4 dependent. Before infection, the levels of total IgE had no significant difference among the three groups of mice. Total and Toxocara-specific IgE in all genotypes of mice increased after infection, and was the highest in normal mice and the lowest in mutant mice. In vitro production of interleukin (IL)-5 and IL-4 by total lung cells was the highest in normal mice and the lowest in mutant mice. CD4+ and CD4- CD8- T lymphocytes, but not CD8+ T lymphocytes produced IL-5 and IL-4 when incubated with anti-CD3 monoclonal antibody (mAb) and lung-adherent cells. These results indicated that IL-5 and IL-4 were produced mainly by CD4+ cells and partly by CD4- CD8- cells, but not by CD8+ cells. In addition, cytokine production by CD4+ cells was affected by the number of CD4 molecules on their surface.

Animals↗

The role of ICAM-1/LFA-1 and VCAM-1/VLA-4 interactions on T helper 2 cytokine production by lung T cells of Toxocara canis-infected mice.

In order to study the effect of costimulatory signals on T helper type 2 (Th2) cytokine production, monoclonal antibodies (mAb) against cell adhesion molecules (CAM) were added to cells in culture obtained from the lungs of Toxocara canis (Tc)-infected mice followed by the determination of interleukin-5 (IL-5) and IL-4 in the supernatants of the culture. ES-stimulated IL-5 production in the supernatant of total lung cells was reduced by 25% when anti-intercellular adhesion molecule-1 (anti-ICAM-1) mAb, anti-CD11a mAb, or both anti-ICAM-1 and anti-CD11a mAb together were added to the culture. The addition of anti-CD18 mAb had no effects. Anti-vascular cell adhesion molecule-1 (anti-VCAM-1) mAb addition also reduced IL-5 production by 60%, although the addition of anti-very late activation antigen-4 (anti-VLA-4) mAb or both anti-VCAM-1 and anti-VLA-4 mAb together were less effective. In the case of anti-CD3 mAb stimulation, similar effects of mAb to CAM were observed. In contrast, IL-4 production induced by anti-CD3 mAb was reduced more markedly by the addition of either anti-ICAM-1 or anti-CD11a mAb than the combination of anti-VCAM-1 and anti-VLA-4 mAb. Similar effects of mAb to CAM were observed on the production of IL-5 and IL-4 by CD4+ T cells purified using a fluorescence-activated cell sorter. Coincubation with adherent cells was necessary for the significant production of IL-5 and IL-4 by CD4+ T cells. These results suggest that the VCAM-1/VLA-4 interaction is more important for IL-5 production by CD4+ T cells in the lungs of Tc-infected mice, and that the ICAM-1/lymphocyte function-associated antigen-1 interaction is more important for the production of IL-4.

Animals↗

[Clinical efficacy of sulbactam/ampicillin in comparison with cefotiam in the treatment of elderly patients with pneumonia].

Clinical efficacy and safety of pareteral sulbactam/ampicillin (SBT/ABPC) was compared with cefotiam (CTM) in a randomized clinical trial of pneumonia in the elderly at 13 National Hospitals of Kyushu island. 37 patients received SBT/ABPC 3 g i.v., b.i.d., and 31 patients received CTM 1 g i.v., b.i.d. for 7 to 14 days. 1. 68 patients (37 for SBT/ABPC and 31 for CTM) were evaluated for safety. No statistical differences were noted in the patients' backgrounds of either group. 2. The clinical efficacy of SBT/ABPC was 96.3% (26/27 cases) while CTM was 75.2% (17/23 cases). This was found to be statistically significant (Fisher's exact test: p < 0.05). 3. 100% of evaluated cases (10 for SBT/ABPC and 4 for CTM) showed bacterial elimination. 4. No side effects were observed in the study. 5. Abnormal laboratory findings were noted in 10.8% (4/37 cases) for SBT/ABPC and 3.2% (1/31 cases) for CTM. The major adverse events were mild elevation of GOT, GPT and A1-P for SBT/ABPC, and mild platelets overproduction for CTM. No statistical differences were noted in both groups. These results are consistent with SBT/ABPC as a highly effective antibiotic in the treatment of elderly patients with pneumonia.

Aged↗

[Diagnostic usefulness of the tuberculin reaction by PPD-B in Mycobacterium avium complex disease].

This study was carried out to clarify the diagnostic usefulness of the skin tests of purified protein derivatives from M. intracellulare (PPD-B) and M. tuberculosis (PPDs). Study subjects consisted of 41 patients with primary infection type of M. avium complex (MAC) disease, 36 patients with pulmonary tuberculosis (TB) and 29 patients with other bacterial respiratory infections including COPD (OB). The patients were sorted out to middle (50-69 y.o.) and old (70-89 y.o.) age groups of each disease. The size of skin redness elicited 48 hours after the PPD-B and PPDs intradermal injections were compared among them. The results were as follows. 1) Both PPD-B and PPDs skin reactions were larger in the middle age group than in the old one for each disease. 2) In PPDs skin tests, the reaction of TB group was the largest among the three diseases. In PPD-B skin tests, that of MAC was the largest. 3) In TB group, PPDs skin reaction was significantly larger than that of PPD-B, while in MAC and OB groups there was no significant difference between the skin reactions of PPDs and PPD-B. 4) Defining significant positive reaction to PPD-B as PPD-B skin reaction exceeding 10 mm and larger than that of PPDs skin reaction, the rate of significant positive reaction to PPD-B was significantly higher in MAC than TB in both age groups. These results showed that the simultaneous skin tests of PPD-B and PPDs were a useful aid in the diagnosis of MAC infection disease when mycobacterial infection diseases were clinically suspected by bacteriological or chest radiographic examinations.

Age Factors↗

[A study of sialylated carbohydrate antigen in patients with benign bronchopulmonary disease].

We studied the levels of carbohydrate antigen (CA 19-9, SLX, CA 50, Span-1, and Dupan-2) in serum, bronchoalveolar lavage fluid, and tissue from patients with benign bronchopulmonary disease. Patients had bronchiectasis, healed pulmonary tuberculosis, pulmonary fibrosis, or other diseases. Bronchoalveolar lavage fluid levels and immunohistochemical findings for lung tissue samples, in the absence of digestive and other diseases, suggested that elevated serum sialylated Lewis(A) (CA 19-9, CA 50, and Span-1) and Lewis(X) (SLX) antigen in patients with benign broncho-pulmonary disease are due to marked production of sialylated carbohydrate antigen in respiratory bronchioles. Common features of patients with benign bronchopulmonary disease include elevated serum carbohydrate antigen levels and bronchiectasis.

Aged↗

Eosinophilia, parasite burden and lung damage in Toxocara canis infection in C57Bl/6 mice genetically deficient in IL-5.

C57Bl/6 mice genetically deficient in interleukin (IL)-5 (IL-5-/-) and mice with the normal IL-5 gene (IL-5+/+) were infected with embryonated eggs of Toxocara canis. IL-5+/+ mice developed a marked eosinophilia in their peripheral bloods and bone marrows after infection. In contrast, the number of eosinophils at these sites actually decreased during the acute phase of infection in IL-5-/- mice. A smaller number of eosinophils infiltrated the lung, liver, heart and skeletal muscle of infected IL-5-/- mice than those of infected IL-5+/+ mice. Eosinophils were not produced in cultures of bone marrow cells from either IL-5+/+ or IL-5-/- mice which were stimulated with excretory secretory antigen of T. canis larvae. The capacity of cells from the bone marrow to differentiate into eosinophils when stimulated in vitro with recombinant murine IL-5 was the same whether the cells were from IL-5+/+ or IL-5-/- mice. Taken together, these results show that an IL-5-like molecule is not produced by the T. canis larvae and that IL-5 produced by host cells is solely responsible for the eosinophilia in mice infected with this nematode. The number and location of T. canis larvae were not altered in the absence of IL-5. In contrast, lung damage in infected IL-5-/- mice was less extensive than that in infected IL-5+/+ mice, although structures resembling Charcot-Leyden crystals were seen in the lungs of both IL-5+/+ and IL-5-/- mice. These results suggest that eosinophils play a role in the pathology in mice infected with T. canis.

Animals↗

A study on temperature dependent vestibular potential: effect of long lasting thermal stimulus and aminoglycoside agent.

Effect of temperature changes on the vestibular receptor was studied using isolated posterior semicircular canals (PSC) of bull frogs. Cupula was removed from the crista. PSC was placed in the inner compartment of the double chamber. Warm or cool water was filled in the outer compartment to change the temperature of the inner compartment. Changes of the spontaneous discharge were recorded from the ampullary nerve. When cooled, the discharge temporarily increased, followed by a gradual decrease. When warmed, it temporarily decreased and then increased, forming response curves of a mirror image. After addition of streptomycin, the temperature dependent response disappeared. These results suggest that the semicircular canal receptor is activated by direct temperature effects.

Action Potentials↗

[Clinical efficacy of imipenem/cilastatin sodium for respiratory infections in patients with lung cancer].

Imipenem/cilastatin sodium (IPM/CS) was administered to 102 patients with respiratory tract infections and lung cancer. Patients with other serious diseases were excluded and a total of 73 patients were enrolled. They were divided into 12 patients who underwent surgery (operated group) and 61 who did not (non-operated group); the latter group included 28 patients treated with anticancer agents or radiation therapy (treated group) and 33 untreated patients (untreated group). IPM/CS was effective in 75% of the patients, both with and without surgery. The drug was effective in 81% of the treated group, although many of the patients had Stage III or more advanced cancer, as well as bronchial occlusion. IPM/CS was also effective in 69% of the untreated group, although many of the patients have serious infections and a PS (Performance Status) of 3 or greater. Thus, IPM/CS treatment achieved good results. Bacteriological studies showed that 3 out of 4 strains in the operated group and 16 out of 18 in the non-operated group were eliminated. Safety was evaluated in all patients. Two patients (2%) experienced side effects and two others (2%) showed abnormal clinical findings, but the symptoms were mild and resolved after discontinuation or completion of therapy. In conclusion, IPM/CS was very effective for treating respiratory infections in patients with lung cancer.

Adenocarcinoma↗

[The distribution and the characteristics in computed tomography (CT) of the lungs in primary Mycobacterium avium complex (MAC) infection].

We investigated the distribution and the characteristics of the lung lesions of patients with primary Mycobacterium avium complex (MAC) infections mainly by computed tomography (CT). They admitted to our hospital during the period from 1984 to 1995 and none of them had a medical history of tuberculosis or other lung diseases. The subjects consisted of fifty patients: fourteen male (average age +/- SD was 66.4 +/- 14.0 year old) and thirty six female (69.0 +/- 11.9 year old). Of 50 patients 24 were M. intracellulare infection, 10 were M. avium infection and others were not identified. First, by using the ratio of slices with lesions on CT to all CT slices from the apex to the base of the lungs, all the patients were divided into two groups; a slight group with less than 15.0% (n = 19) and a severe group with 15.0% or more (n = 31). Next, the density of abnormal shadows in each segment as divided into 5 grades; none (-), minimal (+/-), slight (+), moderate (+2) and severe (+3). The grading was done by taking into account the grade of distribution, density of lesions and destruction of lung parenchym found mainly on CT, and in addition by a standard roentogenographic and tomographic features supplemental. The characteristics frequently observed findings on CT in primary MAC infection patients were nodular (94%), cavitary (74%), bronchiectatic (62%), infiltrative (74%), atelectatic (56%), and pleural-thickened (36%) shadows. Comparing the incidence of segmental lesions in MAC infection patients by segment, it was higher in right and in left lung, but the difference was statistically not significant. As to the number of segments with lesions graded from (+/-) to (+3), many segments were infected unexpectedly: the mean value was 7.7 +/- 1.5 even in the slight group. The proportion of segments with relatively severe lesions graded from (+2) to (+3) in each segment was observed, and the rate in the slight group was 52.6% in S5, 28.9% in S4, 16.7% in S1 (S1 + 2a, b), and 16.7% in S2 (S1 + 2c). In severe group, it was 54.8% in S5, 45.2% in S4, 46.8% in S1 (S1 + 2a, b) 54% in S2 (S1 + 2c), 27.4% in S3 and 26.2% in S6, respectively. The rate of segments with lesions in the lower lobes were less frequent especially in the slight group while it was slightly higher in the severe group. Speculating the initial lesions in the slight group, it was assumed that there might be two types of foci; the one is relatively localized in the beginning and the other is a diffuse type with lesions in many segments even from its early stage. As to the location of initial lesions, the middle lobe and lingula were the most important sites, and the right upper lobe and the left upper division were the next.

Aged↗

The origin of thermally evoked vestibular potential.

The origin of the thermally evoked ampullary nerve action potential was searched using isolated frog posterior semicircular canal (PSC). The PSC was placed in the dish with 2 chambers separating endo- and perilymphatic fluid. Cooling stimulus was given by approximating the iced bar to the ampulla, and induced action potential (CAP) was recorded. When only the endolymph contained Ca2+, no CAP was evoked, while, the perilymph contained Ca2+, CAP was observed. These findings were comparable between with and without cupula. When only the endolymph contained tobramycin (TOB), the spike count did not change. However, when TOB was added into the perilymph, the spike count decreased according to concentration of TOB. When TOB was washed out, the spike count recovered. These findings were also comparable between with and without cupula. The above results indicate that thermally evoked vestibular potentials possibly originate in the hair cell.

Action Potentials↗

Marked eosinophilia in interleukin-5 transgenic mice fails to prevent Trichinella spiralis infection.

In order to study the role of eosinophils in the host defense against Trichinella spiralis infection, worm recovery after infection with T. spiralis was compared between interleukin-5 transgenic (IL-5 Tg) mice with a constant high level of peripheral eosinophils and nontransgenic C3H/HeN mice. No significant difference in the recovery of muscle larvae or adult worms in the small intestine, fecundity of female adult worms, or infectivity of newborn larvae was observed between nonimmunized C3H/HeN and IL-5 Tg mice or C3H/HeN and IL-5 Tg mice immunized with somatic antigen of T. spiralis. However, a significant difference was observed in the fecundity of female adult worms and recovery of muscle larvae between nonimmunized and immunized IL-5 Tg mice or C3H/HeN mice. These results demonstrate that having more eosinophils does not improve immunity against the various aspects of T. spiralis infection.

Animals↗

Eosinophilia, IL-5 level and recovery of larvae in IL-5 transgenic mice infected with Toxocara canis.

Eosinophil counts, interleukin 5 (IL-5) concentrations in peripheral blood and larval recovery after infection with Toxocara canis were compared between IL-5 transgenic (Tg) and nontransgenic counterparts, C3H/HeN mice. In Tg mice characterized by a constant high level of peripheral eosinophils, eosinophils in peripheral blood fell to the lowest level on day 4 of a T. canis infection and then returned to the preinfection level on day 14. Serum IL-5 level fell to the lowest level on day 4 of infection, then recovered rapidly and peaked on day 14 postinfection. In contrast, the eosinophil and IL-5 levels in the peripheral blood peaked on days 11 and 7 of infection, respectively in C3H/HeN mice. The degree of eosinophil infiltration into the lung 4 days after infection was far more pronounced in Tg than C3H/HeN mice. The highest number of larvae recovered from the lungs of infected Tg and C3H/HeN mice occurred on day 4 postinfection. Strains of Tg and C3H/ HeN mice vaccinated with excretory and secretory (ES) antigens of T. canis larvae were infected with T. canis and the recovery of larvae on day 21 analysed. There were no significant differences in the mean number of larvae recovered from nonvaccinated Tg and C3H/HeN mice or vaccinated Tg and C3H/HeN mice. However, significant differences were demonstrated in the mean total number of larvae recovered from vaccinated and nonvaccinated Tg or C3H/HeN mice. These results suggest that immunocompetent cells other than eosinophils may play a significant role in the expulsion and killing of T. canis larvae in infected mice.

Animals↗

Experimental model of vertigo induced by detached otoconia.

Isolated posterior semicircular canals (psc) of bull frogs were used for a model of positional vertigo. Induced ampullary nerve action potentials were recorded. When the cupula was removed and the saccular otoconia were dropped onto the cilia, excitatory, and inhibitory potentials were evoked by changing the psc positions into canal-down and canal-up, respectively. When the otoconia were allowed to stay on the cupular surface, canal-down and canal-up positions also evoked excitatory and inhibitory responses, respectively. When the otoconia were inserted in the canal and were allowed to move, changing the psc positions likewise evoked responses. However, when one end of the canal was closed, these responses disappeared, indicating the efficacy of canal plugging.

Animals↗

Synergism of IL-3, IL-5, and GM-CSF on eosinophil differentiation and its application for an assay of murine IL-5 as an eosinophil differentiation factor.

In order to elucidate the mechanisms of eosinophil differentiation, we examined the effects of combinations of interleukin 5 (IL-5) with IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF) on in vitro differentiation into eosinophils from bone marrow cells of ICR mice. When the amount of added IL-5 was kept constant, IL-3 exhibited dose-dependent production of eosinophils both in the absence and presence of low doses of GM-CSF. In contrast, IL-5 plus GM-CSF showed highly enhanced production of eosinophils, and eosinophil production maximized at a concentration between 10 and 20 U/ml and decreased at higher concentrations. When IL-3 and GM-CSF were kept constant at concentrations of 20 U/ml and 10 U/ml, respectively, the number of eosinophils increased linearly in IL-5-dependent manner in a range from 0.3 to 30 U/ml. These results suggest that IL-3 and GM-CSF act synergistically with IL-5 in in vitro eosinophil differentiation. In addition, we propose a new method for quantifying eosinophil differentiation activity of IL-5.

Animals↗

A highly sensitive and selective method for the determination of Leukotriene B4 in human plasma by negative ion chemical ionization/gas chromatography/tandem mass spectrometry.

We have developed a highly sensitive and highly selective method for the determination of Leukotriene B4 (LTB4) in human plasma using negative ion chemical ionization/gas chromatography/tandem mass spectrometry (NICI/GS/MS/MS) analysis. The developed method was summarized as follows. Deuterated LTB4 (d4-LTB4) was added to human plasma samples as an internal standard, and samples were extracted by a Sep-pak C18 column. Extracted LTB4 was derivatized into the pentafluorobenzyl ester of bis-trimethylsilyl ether (PFB-TMS-LTB4) and quantified on the basis of selected reaction monitoring (SRM) at m/z 299 of [M-PFB-2TMSOH]- by NICI/GC/MS/MS analysis, which was the product ion of [M-PFB]-. The detection limit for the quantification of LTB4 in human plasma was 10 pg ml-1, sufficiently sensitive to determine the concentrations of endogenous LTB4 in human plasma. The plasma level of LTB4 measured in healthy male volunteers was 33.85 +/- 33.91 pg ml-1 (mean +/- S.D. in six volunteers). The technique of MS/MS used in this method offers much greater sensitivity and selectivity than single-stage mass spectrometry. The developed method showed good reproducibility with a simple and rapid extraction procedure, and would be useful for examining the relationship between various disease states and the levels of LTB4 in biological fluids.

Fluorobenzenes↗

Occurrence of interleukin-5 production by CD4- CD8- (double-negative) T cells in lungs of both normal and congenitally athymic nude mice infected with Toxocara canis.

We studied cells in the lungs of BALB/c and BALB/c-nu/nu (nude) mice infected with Toxocara canis, which produced interleukin-5 (IL-5) in in vitro culture with larval excretory-secretory antigen (ESAg). The proportion of CD4+/CD8+/CD4- CD8- cells in lungs of both BALB/c and nude mice was unchanged before and after infection with T. canis. Panning and complement-mediated lysis using monoclonal antibody (mAb) to CD4 showed that CD4+ cells in the lung from both mice produced IL-5. Anti-CD4 mAb suppressed ESAg-stimulated IL-5 production in vitro. In vitro depletion or inhibition of CD8+ cells reduced IL-5 production significantly in some cases, suggesting involvement with IL-5 production. Anti-CD3 mAb enhanced IL-5 production when incubated with or without ESAg. Production of IL-5 was reduced by in vivo depletion of CD4+ cells only and both CD4+ and CD8+ T cells, by intraperitoneal injection with appropriate mAb; IL-5 production was stimulated by anti-CD3 mAb. In contrast, IL-5 production by lung cells of BALB/c mice decreased by more than 90% after simultaneous injection with anti-CD4, anti-CD8 and anti-CD3 mAb, and was not enhanced by anti-CD3 mAb. Similar results were obtained in nude mice. These results suggest that CD4- CD8- T cells, as well as CD4+ T cells, produce IL-5.

Animals↗