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Biomedical subjects

N Kondo

Publications and source records attributed to N Kondo.

At least 397 records · Page 22Linked to original sources

Effect of elimination diets on food-specific IgE antibodies and lymphocyte proliferative responses to food antigens in atopic dermatitis patients exhibiting sensitivity to food allergens.

Peripheral blood mononuclear cells (PBMCs) from patients with atopic dermatitis (AD) selected as being sensitive to hen's egg or cow's milk responded to food antigens, ovalbumin, or bovine serum albumin, with significantly enhanced DNA synthesis compared with the DNA synthesis in PBMCs from nonatopic control subjects and food-sensitive patients with immediate symptoms. Patients were treated with elimination diets. Symptoms of AD had been in remission during elimination diets. The levels of specific IgE antibodies to hen's egg or cow's milk decreased during elimination diets in patients with positive radioallergosorbent test (RAST). In patients with negative RAST, specific IgE antibodies remained negative during elimination diets. The proliferative responses of PBMCs to food antigens also decreased during elimination diets in patients with proliferative responses before elimination diets. Taken together, specific IgE antibodies to food antigens are useful indexes of the effect of elimination diets in food-sensitive patients with AD and positive RAST, and proliferative responses of PBMCs to food antigens are useful indexes of the effect of elimination diets in food-sensitive patients with AD and proliferative responses of PBMCs.

Adolescent↗

Individual diversity of IL-6 generation by human monocytes with lentinan administration.

Effect of in vivo administration of lentinan on IL-6 generation by human peripheral blood monocytes was examined using 5 healthy volunteers. Monocytes isolated from them before and 3 days after intravenous administration of 2 mg lentinan per person were cultured for 2 days and then the levels of IL-6 in the supernatants of cultured monocytes were determined. In vivo lentinan administration elicited an increase in IL-6 generation by monocytes in 3 of 5 cases. Failure to increase IL-6 generation by monocytes in two cases is characteristic of lentinan, since these monocytes generated an apparent level of IL-6 in response to lipopolysaccharide, a potent monocyte activator. Thus, it was demonstrated that lentinan was capable of augmenting IL-6 generation by human monocytes and that there was individual difference in their responsiveness to lentinan.

Acute-Phase Proteins↗

Suppressive effects of elimination diets on T cell responses to ovalbumin in hen's egg-sensitive atopic dermatitis patients.

We investigated the effect of elimination diets on T cell responses to ovalbumin (OA) in hen's egg-sensitive atopic dermatitis (AD) patients. The proliferative responses of both peripheral blood mononuclear cells (PBMCs) and T cells with monocytes to OA decreased after elimination diets, but those to Candida albicans or phytohemagglutinin (PHA) did not decrease after elimination diets. The proliferative responses of CD4+ T cells with monocytes to OA decreased after elimination diets. In these patients, clinical symptoms of AD improved. These results indicate that T cells, especially CD4+ T cells, respond to food antigens in food-specific lymphocyte responses, and that elimination diets may be able to initiate reduction of the responsiveness of food-sensitive T cells, especially CD4+ T cells. Moreover, the surface marker phenotypes of the T cells responding to OA were analysed. Our results showed that CD4+CD45RA+ T cells tended to increase. The increase in circulating CD4+CD45RA+ T cells might function as systemic suppression against immune responses in the skin.

Adolescent↗

Improvement of food-sensitive atopic dermatitis accompanied by reduced lymphocyte responses to food antigen following natural measles virus infection.

Five patients with atopic dermatitis (AD) who were sensitive to hen's egg were observed before and after natural measles virus infection. Within 4 weeks of natural measles virus infection, the eczematous lesions clearly improved in four of the five patients in whom neither offending foods were eliminated, nor anti-allergic drugs, systemic steroids and steroid ointment administered. This was accompanied by reduced proliferative responses of peripheral blood mononuclear cells (PBMCs) to ovalbumin (OA). Another patient showed a transient improvement of AD symptoms, from severe to mild, and thereafter returned to severe accompanied by increased proliferative responses of PBMCs to OA. Radioallergosorbent test (RAST) scores for hen's egg in all five patients did not change in each level in each patient, except the transiently decreased RAST scores for hen's egg in one patient, after the infection. Thus, in patients with AD who are sensitive to food, the improvement of AD symptoms that appeared within 4 weeks of natural measles virus infection was related to reduced proliferative responses of PBMCs to the food antigen following the infection.

Antigens↗

Defective calcium-dependent signal transduction in T lymphocytes of ataxia-telangiectasia.

T-cell functions of two patients with ataxia-telangiectasia were investigated. Patients with ataxia-telangiectasia had reduced percentages of circulating CD3+ cells and CD4+ cells, although neither patient had a reduced percentage of circulating CD8+ cells. The proliferative responses and interleukin-2 production of peripheral blood mononuclear cells to T-cell mitogens were reduced in the patients. The intracellular calcium concentration in T cells or CD4+ cells from both patients was only slightly increased after phytohaemagglutinin stimulation. Moreover, the concentration after OKT3 stimulation was not or only slightly increased in T cells or CD4+ cells from both patients. Our results suggest that the functional defect of T cells is caused by defective Ca(2+)-dependent signal transduction through the CD3 complex of the surface in T cells of ataxia-telangiectasia.

Adolescent↗

Preferential damage to IgM production by ultraviolet B in the cells of patients with Bloom's syndrome.

In most patients with Bloom's syndrome (BS), selective IgM deficiency is commonly found. We examined proliferative responses by incorporation of [3H]-thymidine and the production of immunoglobulin after ultraviolet B (UVB) irradiation in the cells of two patients with BS. With regard to the proliferative responses in peripheral blood mononuclear cells (PBMC) cultured with pokeweed mitogen (PWM), the patients' PBMC were more sensitive to UVB irradiation than controls. Although the effect of UVB irradiation in lymphoblastoid cell lines (LCL) after 0 days of culture showed no difference between one patient and controls, the patient's LCL were more sensitive to UVB than the controls after 3 and 7 days of culture. These results suggest that the proliferative responses of the patient's LCL recovered later than those of controls. IgM production was the most sensitive to UVB in the patients' PBMC and LCL. IgG and IgA production in the patients' PBMC and LCL showed the same sensitivity as controls. From our results, it is suspected that the preferential damage to IgM production by UVB is connected with the selective IgM deficiency of BS.

Adult↗

Expression of secreted immunoglobulin heavy chain genes and immunoglobulin-secreting cells in human lymphocytes.

The numbers of immunoglobulin-secreting cells in peripheral blood mononuclear cells and the expression of mRNA for secreted type of immunoglobulin heavy chains were investigated in healthy children, compared with the percentages of surface immunoglobulin-bearing cells and the expression of mRNA for membrane-bound type of immunoglobulin heavy chains, respectively. Although a difference between expression of mu s mRNA and mu m mRNA was unclear, mu mRNA was well transcribed. The expression of gamma s mRNA or alpha s mRNA was markedly higher than that of gamma m mRNA or alpha m mRNA. However, although the detection methods could be of different sensitivities, the percentage of IgM-, IgG-, or IgA-secreting cells was markedly low, compared with the percentage of surface IgM-, IgG-, or IgA-bearing cells, respectively. Therefore, additional regulation of the pattern of the immunoglobulin gene expression may be exerted at the translational and post-translational stages.

Antibody-Producing Cells↗

Kinetics of hypogammaglobulinemia in patients with common variable immunodeficiency.

We investigated the production of immunoglobulin (Ig) in six patients with common variable immunodeficiency and analyzed the courses of their levels of serum Ig for a period of 8-13 years. In all patients, levels of serum IgM, IgG and IgA were markedly low at the first examination, except for the IgM level in one patient. Improvement of serum Ig levels was observed in the patients in whom Ig production of non-T cells at the first examination and C mu gene expression had been detected to a slight degree, but serum Ig levels remained low in the patients in whom Ig production of non-T cells and C mu gene expression had not been detected. Our results suggest that some hypogammaglobulinemia in common variable immunodeficiency develops or improves with age.

Agammaglobulinemia↗

Abnormal responses of common variable immunodeficiency patients' B cells to Staphylococcus aureus Cowan I and interleukin-2.

Responses of common variable immunodeficiency patients' B cells to Staphylococcus aureus Cowan I (SAC) and recombinant interleukin-2 (rIL-2) varied in our study. T-cell function and IL-2 production were normal, and intrinsic B-cell defects were suggested. Some patients showed no increase in expression of IL-2 receptors on B cells with SAC stimulation, which may be due to impaired maturation stages. Two patients showed an increased level of B cells with IL-2 receptors, suggesting blocked development of intracellular mechanisms. One patient may have a defect in immunoglobulin isotype switching.

Adult↗

Hibernation-associated gene regulation of plasma proteins with a collagen-like domain in mammalian hibernators.

In mammals, hibernation is expressed by only a limited number of species, and the molecular mechanisms underlying hibernation are not well understood. Recently, we have found plasma proteins which disappear from blood specifically during hibernation in a mammalian hibernator, the chipmunk. Here, we report the cDNA cloning of these chipmunk hibernation-related proteins, HP-20, -25, and -27, and analyses of their expression. All three proteins contain a collagen-like domain near the N terminus and are highly homologous to each other. Their mRNAs were detected only in liver in nonhibernating chipmunks, and in hibernating chipmunks, the amounts were reduced to less than 1/10 of those in nonhibernating chipmunks, indicating that HP-20, -25, and -27 mRNA expression is regulated similarly in association with hibernation. Southern blot analyses of the squirrel family with each of chipmunk HP-20, -25, and -27 cDNA revealed that a nonhibernating species (tree squirrel) as well as another hibernating species (ground squirrel) retained the corresponding genes. However, their transcripts were detected only with the hibernating species, and in hibernating ground squirrels, their levels were greatly reduced compared with those in nonhibernating animals, as were the cases with the chipmunk. These observations are the first line of evidence for occurrence of hibernation-associated gene regulation. The results would indicate the commitment of HP-20, -25, and -27 to hibernation and support the idea that genetic controls are involved in mammalian hibernation.

Amino Acid Sequence↗

Bisected N-acetylglucosamine residue of biantennary sugar chains and high-molecular-weight oligosaccharides of neuroblastoma cell membranes.

The carbohydrate moieties of glycoproteins in plasma membrane are known to correlate with the induction of cell differentiation in some kinds of cells. We investigated the asparagine-linked sugar chains of neuroblastoma and ganglioneuroma cell membranes. The acidic oligosaccharides were bi-, tri-, and tetraantennary complex-type sugar chains with Man alpha-->(Man alpha)Man beta-->GlcNAc beta-->(+/- Fuc alpha-->)GlcNAc as their cores. A comparative study of the oligosaccharides of these cells showed that the biantennary complex-type sugar chain with bisecting N-acetylglucosamine residues increased and high-molecular-weight oligosaccharides decreased in ganglioneuroma cells. It is suspected that asparagine-linked sugar chains correlate with the differentiation stage of neuroblastoma.

Acetylglucosamine↗

Urinary oligosaccharide excretion in nephrotic syndrome.

Urinary oligosaccharides from nephrotic syndrome patients were investigated by Bio-Gel P-4 column chromatography and methylation analysis to clarify the electrostatic defects and size barrier defects in the glomerular basement membrane of nephrotic syndrome patients. The levels of urinary oligosaccharides (nmol/mg creatinine) in nephrotic syndrome patients were about 25 times the levels in controls. The ratio of neutral oligosaccharides to sialyl oligosaccharides was about 1:1 in the urine of nephrotic syndrome patients. The levels of neutral oligosaccharides in the urine of nephrotic syndrome patients were about 13 times that of controls. The proportion of trisialylated oligosaccharides in the urine of nephrotic syndrome patients was higher than that in galactosialidosis patients. These findings suggest that electrostatic defects and size barrier defects in the glomerular basement membrane might contribute to the characteristic oligosacchariduria of nephrotic syndrome patients. In addition, the structures of 11 different kinds of oligosaccharides that have not been previously reported were identified in the urine of nephrotic syndrome patients.

Acute Disease↗

Pharmacokinetics of a micronized, poorly water-soluble drug, HO-221, in experimental animals.

N-[[[4-(5-Bromo-2-pyrimidinyloxy)-3-chlorophenyl]amino]carbonyl] - 2-nitrobenzamide (HO-221) is presently under development as an oral anticancer agent with a novel mode of action. However, HO-221 exhibits extremely poor bioavailability after oral administration because it is only slightly soluble in water (0.055 micrograms/ml at 37 degrees C). Our previous study revealed that the micronization of HO-221 to the submicron region improved this oral bioavailability. In this study, the oral pharmacokinetics of this micronized HO-221 was investigated in rats, dogs and monkeys. After oral administration, the agent was moderately absorbed with the Tmax of 6.5-8.0, 17.3-20.0 and 12.0 h, and eliminated with the terminal half-lives of 11.9-15.0, 66.8-78.3 and 42.3 h in rats, dogs and monkeys, respectively. The bioavailability was incomplete (3.7-21.4%). In rats, the plasma concentration did not increase proportionally with increasing oral doses. In dogs, food enhanced the bioavailability 2.2-fold with a standard meal and 3.6-fold with a high fatty meal as compared with fasting conditions.

Administration, Oral↗

Improved oral absorption of a poorly water-soluble drug, HO-221, by wet-bead milling producing particles in submicron region.

N-[[[4-(5-Bromo-2-pyrimidinyloxy)-3-chlorophenyl]amino]carbonyl]-2 -nitrobenzamide (HO-221) is being developed as an anticancer agent with a novel mode of action. HO-221 shows poor oral absorption and is only slightly soluble in water (0.055 micrograms/ml at 37 degrees C). In this study, it was shown that the reduction in particle size of HO-221 to the submicron region (0.453 microm, mean by volume) could be achieved by a wet milling in a decaglycerin monolaurate aqueous solution with small glass beads. The wet milling suspension obtained showed improved dissolution rate and oral absorption in rats. A solid dosage form could also be made from that suspension with addition of sucrose palmitate which prevented aggregation caused by the hydrophobic interaction. The solid dosage form thus obtained showed twice as much oral absorption in dogs as the preparation made by dry milling.

Animals↗

Comparison of the MAST chemiluminescent assay system with RAST and skin tests in allergic children.

The MAST chemiluminescent assay (CLA) system uses enzyme-linked antihuman IgE and a chemiluminogenic substance to determine specific IgE antibodies. The MAST CLA system therefore not only makes unnecessary the precautions required for handling isotopic materials but has the advantage of long-term reagent stability. The MAST CLA system assay protocol consists of three steps: overnight incubation of serum, a 4-hour incubation with enzyme-labeled antibody, and a 30-minute chemiluminescent reaction, which produces a visible image (immunograph) on high-speed instant Polaroid film. We evaluated this MAST CLA system in 47 allergic children and compared the results with those for RAST and skin tests. Good correlations were found between MAST and RAST for house dust, Dermatophagoides farinae, cat, Japanese cedar pollen, egg white, and soybeans, the correlation coefficients being greater than 0.60. When the diagnostic results for MAST and RAST were compared with those of skin test reactions for house dust, Dermatophagoides farinae, cat, Japanese cedar pollen, egg white, and soybeans, MAST had a sensitivity of 85% and a specificity of 82% as compared with 88% and 83% for RAST. Further, an average of 2.1 different allergens were detected in one serum sample. These results suggest that the MAST CLA system can be used to detect specific IgE antibodies and that it provides accurate results for allergic children.

Adolescent↗

mu-Chain gene expression in common variable immunodeficiency.

Three patients with common variable immunodeficiency (CVID) were analyzed for translation from mu mRNA by the cell-free translation method and for expression of mu mRNA by northern blotting. In cases 1 and 2, the mu chain was not detected in the products by cell-free translation nor was mu mRNA detected by northern blotting. In case 3, mu mRNA was detected at a low level. This suggests that the disorders occur between rearrangement of the Ig genes and transcription of the C mu gene in cases 1 and 2, and that the functions of rearrangement and transcription are qualitatively preserved to a certain degree in case 3. Thus, the pathogeneses of CVID are variable and more research on regulatory mechanisms of B cell development is necessary to understand each case of CVID.

B-Lymphocytes↗

[Clinico-pathological study of the mechanism of initiation and progression of right ventricular infarction].

To clarify the mechanism of initiation and progression of right ventricular myocardial infarction, 35 cases were examined among 236 cases of consecutively autopsied hearts. Twenty-six (52%) of 50 cases with posterior left ventricular infarction showed right ventricular infarction, and no statistical differences were observed in the age, gender, and number of impaired vessels among patients with and without right ventricular infarction. However, more proximal occlusion or more extensive thrombi in the right coronary artery did play a very important role in the genesis of the infarction and its progression. Right ventricular dilatation was frequently associated, probably resulted from the functional disorder of contraction and relaxation of the myocardium. Unusual asynchronous ischemia was observed in the right ventricle concomitantly with posterior left ventricular infarction, suggesting the presence of a protective mechanism against ischemia by the abundant collateral circulation of the right ventricle. In conclusion, right ventricular infarction occurs only with the cease of collateral circulation due to proximal occlusion and the presence of long thrombi in the right coronary artery.

Adult↗