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Biomedical subjects

T Kuroume

Publications and source records attributed to T Kuroume.

At least 37 records · Page 2Linked to original sources

Familial congenital hypopituitarism with central diabetes insipidus.

Congenital hypopituitarism (CH) presenting with central diabetes insipidus is typically associated with midline facial deformities or ophthalmological abnormalities. We present three brothers with CH and central diabetes insipidus not associated with any of these predisposing conditions. All three subjects presented with clinical features typical for CH (neonatal hypoglycemia, short stature, protruding forehead, and microgenitalia). All had hypoplastic genitalia indicating in utero gonadotropin deficiency, and all had complete GH deficiency. One represented low levels of thyroid hormones and TSH, indicating central hypothyroidism. Water deprivation examination in two of the brothers demonstrated complete arginine vasopressin deficiency in one and partial deficiency in the other. Magnetic resonance imaging indicated absence of the pituitary stalk, severe hypoplastic anterior pituitary in all three brothers, and absence of any posterior pituitary gland in two of the three. The other sibling had an ectopic posterior pituitary. This first report of familial CH with central diabetes insipidus may represent a previously unknown midline anomaly and provide new insights into the genetic control of pituitary and hypothalamic development.

Antibodies↗

Roxithromycin reduces the degree of bronchial hyperresponsiveness in children with asthma.

We evaluated the effects of a new semisynthetic macrolide antibiotic, roxithromycin, on the bronchial hyperresponsiveness to histamine in children with asthma. Twelve hospitalized asthmatic children, aged 11 to 15 years (mean age, 12.9 years), were enrolled in this study. They were treated with 150 mg of roxithromycin once a day orally for 8 weeks without any side effects. The PC20 value 4 or 8 weeks after the administration of roxithromycin increased significantly over the initial values (p < 0.05, p < 0.01, respectively). No significant change was observed in serum theophylline concentrations during this study. Serum cortisol level in the morning did not change after the administration of roxithromycin for 4 weeks. These results suggest that administration of roxithromycin may act favorably in the treatment of childhood asthma.

Adolescent↗

Effect of theophylline on serum uric acid levels in children with asthma.

This study was undertaken to investigate the effect of theophylline on serum uric acid levels in children with asthma. Twenty-seven asthmatic children, including 21 patients who were treated with slow-release theophylline and 6 patients not receiving any type of theophylline preparation, were enrolled in this study. Serum uric acid levels were increased in the asthmatic children treated with theophylline compared to those not receiving this agent (6.28 +/- 0.29 mg/dl, mean +/- SEM, vs. 4.82 +/- 0.52 mg/dl, p < 0.05). A significant positive correlation between the serum levels of uric acid and theophylline was demonstrated in the patients of this study (rs = 0.596, p < 0.01). All the patients in whom theophylline administration was stopped showed significant decreases in serum uric acid levels (p < 0.05). From these results, we conclude that theophylline increases serum uric acid levels in children with asthma, just as it does in adult asthmatics.

Adolescent↗

Age-related changes in bronchial hyperreactivity during the adolescent period.

To evaluate the influence of bronchial hyperreactivity on the improvement of asthma seen during adolescence, age-related changes of bronchial reactivity to methacholine (BRm) in adolescence were evaluated in two studies. Study 1 included 261 asthmatic children and 89 controls, aged 6-26 years, and in Study 2, yearly BRm variations from age 11 to 16 years of 23 asthmatic children of study 1 were studied. Methacholine inhalation challenge was performed by using an oscillation method; that is, respiratory resistance (Rrs) was directly measured by an oscillation technique, and subsequent doses were then doubled, until a twofold increase in Rrs from the baseline was reached. The cumulative dose of methacholine at the inflection point of the Rrs was considered to represent the BRm. From ages 6 to 9, Dmin in the asthmatic children were low (from 2.07 units to 1.38 units), but after age 12, the value gradually increased, and finally became sustained after age 16 (from 2.27 units to 4.80 units). These same age-related changes were seen in the age-matched controls. From ages 6 to 11, Dmin in the control children were also low (from 8.07 units to 12.9 units), but after age 12, Dmin gradually increased, and finally became sustained after age 16 (from 18.5 units to 43.2 units). However, for each year, the Dmin of the asthmatic children were significantly lower than those of the controls. Further, the mean of yearly Dmin variation from age 13 was less than that of younger subjects (from 0.65 unit/year to 0.92 unit/year, from 1.16 units/year younger subjects (from 0.65 unit/year to 0.92 unit/year, from 1.16 units/year to 4.16 units/year, respectively). We, therefore, concluded that the natural age-related BRm changes and the increased stability of yearly BRm variation that occur in adolescence may play a role in the improvement of childhood asthma seen during this period.

Adolescent↗

Increased cytokine levels and abnormal response of myeloid progenitor cells to granulocyte colony-stimulating factor in a case of severe congenital neutropenia. In vitro effects of stem cell factor.

PURPOSE: The cytokine levels and the in vitro granulopoiesis were studied to evaluate the mechanism of impaired granulopoiesis in severe congenital neutropenia (SCN). PATIENT AND METHODS: The patient was a 5-year-old boy with SCN. We assayed the colony-stimulating activity (CSA) produced by peripheral blood (PB) cells from the patient. The plasma levels of cytokines were measured using enzyme immunoassay. These included granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 1 alpha (IL-1 alpha), IL-1 beta, IL-2, IL-3, IL-4, IL-6, and tumor necrosis factor-alpha. The effects of IL-3 and stem cell factor (SCF) on the proliferation of granulocyte-macrophage colony-forming cells (GM-CFCs) were studied. RESULTS: CSA produced by PB cells from the patient was almost the same as in the healthy control. The level of endogenous G-CSF was elevated to 334 pg/ml, and GM-CSF, IL-2, IL-3, and IL-6 were slightly elevated. The numbers of GM-CFCs were markedly depressed in the presence of G-CSF alone and showed no increment on additional stimulation by IL-3. SCF in combination with G-CSF significantly augmented the proliferation of GM-CFCs. CONCLUSIONS: These findings suggest that some cytokines including G-CSF may be elevated in SCN patients and that CSF may play an important role in the pathogenesis of SCN.

Colony-Stimulating Factors↗

Bradykinin is less potent in causing airway microvascular leakage in immature than in adult guinea-pigs. Role of neutral endopeptidase.

To study the effect of maturation on bradykinin-induced airflow obstruction and airway microvascular leakage, we measured changes in both lung resistance (RL) and extravasation of Evans Blue dye in anaesthetized immature (aged 12 +/- 1 days) and adult guinea-pigs (aged 77 +/- 2 days). After measurement of RL after i.v. administration of bradykinin (2.5, 5 and 10 nmol/kg) or vehicle (0.9% NaCl), dye extravasation in the lower airways was examined in the same animal. Bradykinin did not cause a significant increase in RL in immature airways, whereas even 2.5 nmol/kg induced a significant elevation in adult airways. Bradykinin-induced extravasation of Evans Blue dye was greater in adult than in immature animals. Phosphoramidon (2.5 mg/kg), a neutral endopeptidase inhibitor, did not abolish the age-related difference in the amount of dye extravasated, suggesting that mechanisms other than changes in neutral endopeptidase activity may be responsible for the lower potency of bradykinin in inducing airway microvascular leakage in immature airways.

Aging↗

Platelet-activating factor-induced enhancement of superoxide anion generation in guinea-pigs.

We studied whether platelet-activating factor (PAF) enhances superoxide anion (O2-) generation in guinea-pigs. The production of O2- was assayed by chemiluminescence, using a Cypridina luciferin analog as a highly sensitive and specific probe for O2-. I.v. administered PAF significantly enhanced phorbol myristate acetate- or N-formyl-methionyl-leucyl-phenylalanine-induced O2- generation by guinea-pig alveolar macrophages or by polymorphonuclear leukocytes in a dose-dependent manner. The priming effect of PAF on O2- generation was maximal in cells harvested 5 min after administration of PAF. These responses were completely inhibited by administration of WEB 2086, a specific PAF receptor antagonist, or ONO-3708, a specific thromboxane A2 receptor antagonist, suggesting that the effects were mediated through the PAF receptor and thromboxane A2 generation. PAF might contribute to airway inflammation by enhancing O2- formation in addition to exerting other effects such as smooth muscle contraction or microvascular leakage.

Animals↗

Dipyridamole enhancement of drug sensitivity in acute lymphoblastic leukemia cells.

The effect of dipyridamole (DPM) on cell sensitivity to anticancer drugs was examined in acute lymphoblastic leukemia (ALL) cell lines. We established two ALL cell lines (KMO-90 and KMO-R) from bone marrow samples of a 12-year-old girl with ALL. The drug concentrations needed to reduce optical density to 50% of that of control cells (IC50) showed that KMO-R was about twofold more resistant to doxorubicin (DOX), mitoxantrone (MIT), vincristine (VCR), and etoposide (VP-16) than was KMO-90. Considering that both KMO-90 and KMO-R were established from a patient with ALL at the time of presentation and relapse, respectively, these two cell lines might be novel and useful models for research into the acquisition of drug resistance in ALL cells. Although cytotoxicity of DPM in KMO-90 was about 6% at 1 microgram/ml, DPM enhanced cell sensitivity to DOX, MIT, VCR, and VP-16 at this concentration. Cytotoxicity of DPM in KMO-R was less than 5% at 1, 5, and 10 micrograms/ml. In KMO-R, DPM enhanced cell sensitivity to these four drugs in a dose-dependent manner. The plasma concentrations achieved by oral administration of DPM is about 1 microgram/ml. At clinically achievable concentrations, DPM enhanced cell sensitivity to DOX, MIT, VCR, and VP-16 in both KMO-90 and KMO-R, thus showing DPM to be a useful agent for potentiating anticancer chemotherapy of hematopoietic malignancy.

Administration, Oral↗

Fatal pulmonary haemorrhage and crescentic glomerulonephritis without autoantibodies: a paediatric case report.

The case of an 8-year-old girl who had a fatal pulmonary haemorrhage and crescentic glomerulonephritis without autoantibodies is presented. Circulating anti-glomerular basement membrane antibodies, circulating immune complexes and anti-neutrophil cytoplasmic autoantibodies were not detected. To our knowledge this is the youngest reported case of the disease.

Antigen-Antibody Complex↗

A case of Johanson-Blizzard syndrome complicated by diabetes mellitus.

We report a girl with Johanson-Blizzard syndrome complicated by diabetes mellitus. She presented several characteristic malformations, such as aplasia of the alae nasi, deafness, dwarfism, absence of permanent teeth and malabsorption caused by disturbance of pancreatic exocrine function. At 11 years of age, glycosuria was detected at a routine outpatient examination. Repeated oral glucose tests showed a slowly progressive decline of insulin secretion and elevated blood glucose levels. The responsive secretion of insulin to glucagon or arginine loading was also low. The blood level of HbAlc was elevated over 9%. Based on these findings, insulin therapy was started when the patient was 13 years old. Our case suggests that diabetes mellitus might be considered as one of complications of Johanson-Blizzard syndrome.

Abnormalities, Multiple↗

Attenuation of tachykinin-induced airflow obstruction and microvascular leakage in immature airways.

1. To study the effect of maturation on substance P (SP)- and neurokinin A (NKA)-induced airflow obstruction and airway microvascular leakage (MVL), we have measured changes in both lung resistance (RL) and extravasation of Evans blue dye in anaesthetized immature (aged 14 +/- 1 days) and adult guinea-pigs (aged 80 +/- 3 days). 2. RL and its recovery after hyperinflation at 5 min were measured for 6 min after i.v. SP (0.2, 1 and 30 nmol kg-1), NKA (1 and 10 nmol kg-1) or vehicle (0.9% NaCl). After measurement of RL, MVL in trachea, main bronchi and intrapulmonary airways was also examined. 3. The order of potency in inducing airflow obstruction did not change with age (NKA > SP) but immature animals required a larger dose of SP or NKA than adults to cause a significant increase in RL. 4. The order of potency in inducing airway microvascular leakage was SP > NKA in both immature and adult animals. The amount of extravasated dye after SP was significantly less in immature airways, especially in central airways. 5. Phosphoramidon (2.5 mg kg-1), a neutral endopeptidase (NEP) inhibitor, significantly increased RL after 0.2 nmol kg-1 SP only in adult airways. Phosphoramidon enhanced the dye extravasation after 0.2 nmol kg-1 SP in both immature and adult airways with a significantly greater amount of dye in adult animals, suggesting that mechanisms other than changes in NEP activity may be responsible for this age-related difference. 6. RL after hyperinflation following SP was not correlated with the degree of extravasation of Evans blue dye in immature animals, whereas it was closely correlated in adult animals. 7. SP and NKA may be less potent in causing both bronchoconstriction and microvascular leakage in immature airways. 8. Airway oedema caused by microvascular leakage may contribute less in immature airways to airflow obstruction after SP or NKA.

Aging↗

The concentration of bovine IgG in human breast milk measured using different methods.

The bovine IgG concentration in human breast milk was measured using three different methods: competition radioimmunoassay (RIA), competition enzyme-linked immunosorbent assay (ELISA) and sandwich ELISA. In 36 samples of human breast milk taken from mothers on diets including cow's milk, the concentration of bovine IgG was significantly higher when measured by either competition RIA or ELISA (mean 324.9 +/- 97.4 ng/ml and 396.7 +/- 58.7 ng/ml, respectively) than by sandwich ELISA (3.44 +/- 0.48 ng/ml). In 7 samples of human breast milk taken from mothers on cow's-milk-free diets of more than one month, the concentration of bovine IgG was still within a detectable range (112.3 +/- 41.4 ng/ml) using competition ELISA, whereas it was not detected when using sandwich ELISA, suggesting that competition ELISA might measure some unknown substances in addition to bovine IgG. Gel filtration of pooled human breast milk revealed three large fractions. The concentration of bovine IgG in every fraction was significantly higher using competition compared with sandwich ELISA, suggesting that the difference between these assays does not result from measuring different quantities of bovine IgG, or of fragments of this protein. The time course of the bovine IgG level was different between each human breast milk sample after taking cow's milk. We showed that human breast milk contains bovine IgG at a concentration of approximately 3 ng/ml when analysed using sandwich ELISA. This level is comparable to the quantity of either casein or of beta-lactoglobulin in human breast milk. Bovine IgG might be an important allergen in cow's milk allergy due to the quantity in human breast milk.

Animals↗

Influence of environmental mite antigen on anti-mite antibody production in mice.

To investigate the effects of environmental mite antigen on anti-mite antibody production in mice, a mite-free breeding system was established. The amount of Dermatophagoides farinae (Df) antigen was measured using the ELISA inhibition method. Df antigen was detected in the wood-chip bedding used in our conventional breeding system for 1 week (2.55 +/- 0.79 micrograms/g sample) and 2 weeks (8.96 +/- 3.27 micrograms/g sample). Df antigen was also detected in the standard diet (0.4 micrograms/g sample) in the conventional system, whereas no antigen was detected in the case of the mite-free breeding system. Neither anti-Df IgE nor IgG antibody was detected before immunization, either in mice raised in the mite-free breeding system or in mice raised in the conventional system. Primary and secondary antibody production after immunizations with 1 or 10 micrograms Df antigen was studied in the mouse bred in the conventional and in the mite-free breeding system. Primary anti-Df IgE antibody response of the conventional group was greater than that in the mite-free group after immunization with either dose of 1 and 10 micrograms Df antigen. Primary anti-Df IgG antibody response was greater in the conventional than the mite-free group after immunization with 1 microgram Df antigen. Secondary IgE and IgG responses of the conventional group were greater than the mite-free group after immunizations with 10 micrograms Df antigen. These results suggest that anti-Df antibody production is enhanced by chronic exposure to Df antigen in the environment.

Animal Feed↗

Erythromycin increases gastric antral motility in human premature infants.

The aim of this study was to determine if erythromycin (EM), which is a potent motilin agonist, alters gastrointestinal motility in premature infants. Six infants who were born after 23-30 weeks gestation and weighed 825-1,408 g at birth were studied when 6-31 days old. Intraluminal pressure changes within the gastric antrum and proximal duodenum were recorded. We infused EM 0.75 mg/kg intravenously for 15 min and we compared gastric and duodenal contractions for 30 min between before and after the initiation of EM infusion. In these preterm infants the migrating complex was not present, and was not induced by EM. However, in all 6 infants EM increased nonpropagating antral clusters of contractions (p < 0.05). The antral motility index increased 4-fold (p < 0.05). We concluded that human premature infants have functioning motilin receptors.

Duodenum↗

Transport of triiodothyronine by erythrocytes from premature and term infants.

To analyze hypothyroxinemia in low birth weight (LBW) infants, the initial uptake of T3 into erythrocytes from term and premature infants was measured. Thirty-eight infants and 18 prepubertal children as controls were subjected in this study. The infants were divided into group 1 (premature infants; below 2,500 g, n = 12) and group 2 (term infants; 2,501-3,500 g, n = 26). Infants with LBW for gestational age were excluded from this study. Vmax for group 1 (mean +/- SE, 6.4 +/- 0.5 pmol/min/10(8) cells), having low thyroid hormone levels, was significantly less than in group 2 (9.0 +/- 0.7 pmol/min/10(8) cells; p < 0.05). Mean Vmax for both groups exceeded normal controls (3.9 +/- 0.3 pmol/min/10(8) cells; p < 0.01). Km in the perinatal period varied widely and was essentially the same as in the normal controls. These findings indicate that T3 uptake by erythrocytes of newborns may possibly be high regardless of maturation stage and blood levels of thyroid hormones may be reflected not by change in the affinity of the transport system but by that in the number of membrane carriers.

Biological Transport↗