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Biomedical subjects

A Komiyama

Publications and source records attributed to A Komiyama.

At least 37 records · Page 2Linked to original sources
PubMed2000

Theophylline induces neutrophil apoptosis through adenosine A2A receptor antagonism.

This study was designed to determine whether theophylline would augment granulocyte apoptosis via a mechanism of adenosine A2A receptor antagonism. A selective adenosine A2 receptor agonist (CGS-21680, 1 microM) exhibited the most efficient potency for decreasing neutrophil apoptosis for 16 h from 63+/-5 to 19+/-4% (P < 0.001); it exerted poor and adverse effects on eosinophil survival. A selective protein kinase A inhibitor KT-5720 (10 microM) reversed the capacity of dibutyryl cAMP but not CGS-21680 to induce an inhibitory effect on neutrophil apoptosis, suggesting that occupancy of adenosine A2 receptors inhibit neutrophil apoptosis by a cAMP-independent mechanism. Theophylline derivatives show the following pattern of potency for inducing neutrophil apoptosis competing with CGS-21680: 8-phenyltheophylline = 8-p-sulfophenyltheophylline > theophylline >> enprofylline. This pattern is consistent with the affinity established for A2A receptors. Theophylline demonstrated an additive effect to that of anti-Fas antibody (CH11, 1 microg/mL) in inducing neutrophil apoptosis, but not to that of adenosine deaminase or KF-17837 (a selective A2 receptor antagonist; 1 microM), suggesting conflicting effects on the receptor antagonism. These findings suggest that theophylline has an immunomodulatory action on neutrophil apoptosis via a mechanism of A2A antagonism.

Adenosine↗
PubMed2000

Genetic and long-term data on a patient with permanent isolated proximal renal tubular acidosis.

UNLABELLED: A 12-year-old girl presented with permanent isolated proximal renal tubular acidosis (pRTA), glaucoma, band keratopathy, mild cataract and short stature. Severe metabolic acidosis was caused by the impairment of bicarbonate reabsorption in the proximal tubules and alkali therapy improved her acidaemia. A homozygous G to A transition at nucleotide 1,678 in the basolateral kidney type Na+/HCO3- (kNBC) cotransporter gene SLC4A4, which is critical in HCO3- resorption in renal proximal tubules, was identified. Her height and height velocity (HV) were very low (-4.0 SD and -4.4 SD, respectively) before alkali treatment, but both improved after initiating alkali therapy at the age of 2 years and 3 months. The patient's body height and HV were 131.5 cm (-2.7 SD) and 4.0 cm (-2.0 SD), respectively at the age of 12 years. CONCLUSION: This case demonstrates that early administration of alkali therapy and sustained correction of acidosis, even if inadequate to correct the metabolic acidosis, can markedly improves growth in permanent isolated proximal renal tubular acidosis.

Acidosis, Renal Tubular↗
PubMed2000

Alterations of basement membrane in di-isopropanolnitrosamine-induced carcinogenesis of the rat thyroid gland: an immunohistochemical study.

Alterations of basement membrane (BM) in di-isopropanolnitrosamine (DIPN)-induced carcinogenesis of the rat thyroid gland were examined by means of immunohistochemical localization of collagen type IV (CN-IV), laminin (LN), and fibronectin (FN) in prenodular and nodular thyroid lesions, correlating with the morphogenesis and proliferative activity of these lesions. Adult male rats of the Wistar strain were injected s.c. in the back with DIPN, and the thyroid glands were removed at the 15th and 30th week of treatment. Each of 133 thyroid lesions was histochemically analyzed. The follicular epithelial BM as revealed by CN-IV and LN was discontinued or completely lost during the progression of thyroid lesions from pre-nodular to nodular lesions and finally overt carcinomas. At the same time, the BM of vascular endothelial cells demonstrated a loss of dense capillary networks of follicles, a sinusoidal dilatation and, predominantly in carcinomas, development of interstitial-type blood vessels. However, FN, which was hardly stained in the normal thyroid tissue, was remarkably deposited in the interstitium of invasive carcinomas. These observations strongly suggested that alterations of BM structure play a key role in the morphogenesis of rat thyroid tumors, and that the expression of FN is an important step in the invasive growth of thyroid tumors.

Animals↗
PubMed2000

Stressful delivery influences circulating thrombopoietin (TPO) levels in newborns: possible role for cortisol in TPO-mpl binding.

The regulation mechanism of circulating thrombopoietin (TPO) level in human newborns remains unknown. In the present study, we examined whether the TPO concentrations in cord blood were influenced by the difference in the delivery method and the presence or absence of maternal/fetal complications. Cortisol levels were simultaneously measured to assess the adrenal response of fetuses. Both the TPO level and the cortisol level were substantially greater in the neonates delivered vaginally with and without the complications than in those delivered by cesarean section without the complications. The binding assay showed that the incubation of mpl(+)/BaF3 cells with cortisol gave rise to a significant decrease in the binding sites of TPO. These results suggest that the stress to the fetuses near the time of delivery affects the cord blood TPO levels, which may be mediated in part by the action of cortisol on the TPO-mpl binding system.

Binding Sites↗
PubMed2000

Detection of Bruton's tyrosine kinase mutations in hypogammaglobulinaemic males registered as common variable immunodeficiency (CVID) in the Japanese Immunodeficiency Registry.

CVID is frequently diagnosed in male and female individuals with hypogammaglobulinaemia of unknown aetiology. To examine the possibility that sporadic male cases with X-linked agammaglobulinaemia (XLA), which is caused by mutations in the Bruton's tyrosine kinase (Btk) gene, might be misregistered as having CVID, we employed a flow cytometric test to identify XLA in hypogammaglobulinaemic males registered as CVID in the Japanese Immunodeficiency Registry. From 30 male cases registered as having CVID between 1992 and 1998, we selected 21 males with low or unreported peripheral B cell counts. Blood samples could be obtained from 11 patients and their mothers. Using flow cytometric analysis, the Btk-deficient status in monocytes was demonstrated in seven out of nine cases with decreased numbers of peripheral B cells. The diagnosis of XLA was confirmed in each of the seven patients by demonstration of Btk gene mutations in the patients or cellular mosaicism in the mother. This study demonstrates misregistration of XLA as CVID.

Agammaglobulinaemia Tyrosine Kinase↗
PubMed2000

Unfavorable lipid profiles in mild obesity with excess body fat percentage.

BACKGROUND: The aim of the present study was to investigate the usefulness of subclassifications of overweight children using the body fat percentage (Fat%) to predict the serum lipid profile. METHODS: School children (431, 236 boys and 195 girls) aged 9-12 years were divided into three obesity groups (non-, mild and advanced obesity) and were further divided into two subgroups according to the Fat% measured by bioelectrical impedance analysis. The mean fasting serum lipid levels were also evaluated. RESULTS: In the non-obesity and the advanced obesity groups, the Fat%-based subclassification demonstrated no essential differences in lipid profiles or in the prevalence of hyperlipidemia between the two subgroups. However, in the mild obesity group, the levels of low-density lipoprotein cholesterol and triglyceride and the atherogenic index were significantly higher and the high-density lipoprotein cholesterol level was significantly lower in the adipositic subgroup (Fat% > or = age/sex-specific cut-off value) than in the non-adipositic subgroup. Multiple comparison of lipid levels among all six categories of children indicated that the adipositic subgroup of mild obesity had no advantage over the advanced obesity group with respect to the atherogenic potential and that the non-adipositic subgroup of mild obesity showed no additional risks compared to the non-obesity group. Moreover, the prevalence of hyperlipidemia in the adipositic subgroup of mild obesity (50.0%) was significantly different from that in its non-adipositic counterpart (13.3%) and was equivalent to that in the advanced obesity group. CONCLUSIONS: These results suggest that Fat% evaluation is useful to divide mildly obese children into two distinct subtypes based on serum lipid profiles and that the excess Fat% in mildly obese school children is a predictor of atherogenesis.

Adipose Tissue↗
PubMed2000

Preperitoneal fat thickness in childhood obesity: association with serum insulin concentration.

BACKGROUND: The clinical significance of visceral fat accumulation in childhood obesity has remained controversial. METHODS: In 35 subjects (18 boys and 17 girls) aged 9-15 years, visceral and subcutaneous fat were estimated by measuring the maximum thickness of preperitoneal fat (Pmax) and the minimum thickness of subcutaneous fat (Smin) in the upper median abdomen, respectively, by ultrasonography. The associations with fasting serum insulin levels converted to logarithm (log(IRI)) were studied for six obesity-related indices, including the obesity index, body fat percentage, waist-to-hip circumference ratio (WHR), Pmax, Smin and the ratio of Pmax to Smin (abdominal wall fat index, AFI). RESULTS: In girls, the log(IRI) was positively correlated with the Pmax, obesity index, body fat percentage and Smin. In contrast, the log(IRI) was positively correlated only with the Pmax and Smin in boys. There were no significant correlations between the log(IRI) and the WHR or AFI in either sex. The Pmax revealed the highest correlation with the log(IRI) in both boys (r = 0.703, P < 0.001) and girls (r = 0.921, P < 0.0001). CONCLUSION: These results indicate the important contribution of visceral fat accumulation to the development of hyperinsulinemia, regardless of sex. Accordingly, it is suggested that evaluating Pmax by ultrasonography may be the most sensitive and reliable method of predicting insulin resistance-associated metabolic derangements in children, compared with other conventional indices of obesity.

Adipose Tissue↗
PubMed2000

Extraocular muscle responses to high dose intravenous methylprednisolone in myasthenia gravis.

Three patients with generalised myasthenia gravis and three with ocular myasthenia gravis received two to five courses of high dose intravenous methylprednisolone because of the failure of standard immunomodulating therapies. Changes in myasthenic signs were assessed using a four step system for grading muscle weakness and fatiguability in 10 test items. Although a brief and modest amelioration was found from day 1 to day 2 after the initial infusion in two patients with generalised myasthenia gravis, all three experienced a prolonged phase of worsening followed by improvement before the next course. Conversely, for two of the patients with ocular myasthenia gravis, a transient but dramatic improvement of ptosis and ocular immobility was noted from 90 minutes to 5 hours after initiating the first infusion, followed by mild or no exacerbation. This 3 hour improvement may be related not only to possible differences in the neuromuscular junction, but also to corticosteroids unmasking the central adaptation for the peripheral ocular muscle weakness by increasing the acetylcholine release.

Acetylcholine↗
PubMed2000

Eye deviation in patients with one-and-a-half syndrome.

To understand malalignments of the visual axes in one-and-a-half syndrome, we measured eye positions in 4 patients with this syndrome under two conditions: with Frenzel goggles to prevent eye fixation and without Frenzel goggles. When fixation was prevented with the Frenzel goggles, all patients showed mild outward deviation in both eyes. Removal of the Frenzel goggles elicited adduction of the eye ipsilateral to the side of the lesion for fixation, with greater outward deviation of the contralateral eye (acute stage), or adduction of both eyes to midposition for biocular fixation (convalescent stage). In 3 patients whose outward eye deviation with Frenzel goggles was greater on the ipsilateral side, a transition from one-and-a-half syndrome to ipsilateral internuclear ophthalmoplegia was noted, whereas a transition to ipsilateral gaze palsy was seen in the one patient whose deviation was greater on the contralateral side. These findings suggest that in one-and-a-half syndrome patients, the eyes tend to be in divergent positions when fixation is prevented; ipsilateral eye deviation may result from medial longitudinal fasciculus involvement, and contralateral eye deviation may result from paramedian pontine reticular formation involvement. Viewing a target may lead to a secondary deviation or adaptation of eye positions for fixation.

Aged↗
PubMed2000

Thrombopoietin enhances neutrophil production by bone marrow hematopoietic progenitors with the aid of stem cell factor in congenital neutropenia.

We examined the effects of granulocyte colony-stimulating factor (G-CSF), stem cell factor (SCF), and thrombopoietin (TPO), alone or in combination, on the generation of neutrophils by bone marrow (BM) cells from three patients with severe congenital neutropenia (SCN) through the use of a serum-deprived liquid culture system. Synergistic effects of G-CSF and SCF on the neutrophil production by BM CD34+CD38+c-kit+ cells were observed in SCN patients as well as in normal controls. The addition of TPO to the culture containing G-CSF and SCF further augmented the growth of neutrophils in the two groups. Single-cell culture experiments revealed that the three-factor combination caused increases in both the number and size of neutrophil colonies compared with G-CSF + SCF in normal BM cells, whereas only a significant increment in the colony size was observed in SCN patients. Even in the presence of SCF or SCF + TPO, the concentrations of G-CSF necessary for the substantial production of neutrophils by CD34+CD38+c-kit+ cells were higher in two patients compared with the levels obtained by normal control cells. In addition, TPO did not accelerate the maturation of neutrophilic cells supported by G-CSF + SCF. When BM CD34+CD38-c-kit+ cells were targeted, the addition of TPO to the culture containing G-CSF and SCF was required for significant neutrophil colony growth in the two groups. These results suggest that TPO enhances the G-CSF-dependent neutrophil production with the aid of SCF in this disorder.

ADP-ribosyl Cyclase↗
PubMed2000

Effects of theophylline on human eosinophil functions: comparative study with neutrophil functions.

The understanding of theophylline as a bronchodilator has been reconsidered in recent years. We undertook to determine its immunomodulatory actions in granulocytes and elucidate their mechanism. Preincubation of neutrophils with theophylline (10(-5) to 5 x 10(-3) M) had a biphasic effect on O2(-) production stimulated with N-formyl-methionyl-leucyl-phenylalanine or C5a. Theophylline potentiates O2(-) production via adenosine A(2A) receptor antagonism induced by receptor-linked agonists from neutrophils, but not from eosinophils. The addition of theophylline caused a significant decline in neutrophil chemotaxis at lower concentrations than those for eosinophil motility. Theophylline reduces neutrophil chemotaxis via adenosine A1 receptor antagonism. At high concentrations, with an intracellular cAMP accumulation as a result of phosphodiesterase (PDE) inhibition, theophylline also exerts an inhibitory effect on the O2(-) production and chemotaxis of both types of cells. The difference in theophylline's effect on neutrophils and eosinophils appears to depend on the existence of specific adenosine receptors. Theophylline thus modulates granulocyte functions in association with specific adenosine receptor antagonism and cAMP-PDE inhibition.

Bronchodilator Agents↗
PubMed2000

B cell development and primary immunodeficiencies with hypogammaglobulinemia.

The differentiation of B cells along the pathway of B cell development has been well characterized. In the bone marrow, the differentiation from pro-B cells to immature B cells can be defined by several surface antigens, such as a surrogate light chain. Immature B cells become mature B cells and then circulate in the peripheral blood as naive B cells. In the peripheral lymphoid tissues, naive B cells differentiate into memory B cells, which express the CD27 molecule, or plasma cells. Primary immunodeficiencies with hypogammaglobulinemia are caused by defects of the specific molecules which are needed for the B cell differentiation. Recent studies of the genes responsible for such immunodeficiencies have clarified B cell development as well as their pathogenesis. We discuss here the molecules affecting the B cell development and primary immunodeficiencies with hypogammaglobulinemia.

Agammaglobulinemia↗
PubMed2000

[Lymphocytic infundibuloneurohypophysitis during the first remission in acute lymphoblastic leukemia].

A 15-year-old girl developed acute lymphoblastic leukemia (ALL). The patient was treated according to the 13th protocol of the Tokyo Children's Cancer Study Group, and thereafter remained free of disease. However, at the age of 20, she complained of polyuria, polydipsia and amenorrhea. Hematological or meningeal relapse was ruled out on the basis of clinical and laboratory findings. The plasma concentrations of GH, TSH, LH, FSH, ACTH and ADH were low or below the detectable limits. There was no increase in urine osmolarity after water deprivation. Arginine, LH-RH, TRH and CRH tolerance tests revealed no or low responses of GH, LH/FSH, TSH, and ACTH/cortisol, respectively. Magnetic resonance imaging demonstrated thickening of the pituitary stalk, which was homogeneously enhanced by gadolinium administration. A biopsy specimen showed fibrosis and infiltration of CD8-positive T lymphocytes in a portion of the pituitary stalk, whereas the adenohypophysis was normal. In addition, no leukemic cells were observed in the samples. Thus, a diagnosis of lymphocytic infundibuloneurohyophysitis (LIN) was established. All the symptoms were improved by treatment with hydrocortisone, L-thyroxine, desamino-8-d-arginine vasopressin, estrogen and gestagen. This is the first reported case of ALL complicated by LIN.

Adult↗