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Biomedical subjects

T Kuroume

Publications and source records attributed to T Kuroume.

At least 55 records · Page 3Linked to original sources

A new point mutation in the deoxyribonucleic acid-binding domain of the vitamin D receptor in a kindred with hereditary 1,25-dihydroxyvitamin D-resistant rickets.

Hereditary 1,25-dihydroxyvitamin D [1,25-(OH)2D]-resistant rickets (HVDRR) is a rare disorder characterized by rickets, alopecia, hypocalcemia, secondary hyperparathyroidism, and normal or elevated serum 1,25-dihydroxyvitamin D levels. We describe a patient with typical clinical characteristics of HVDRR, except that elevated levels of serum phosphorus were present coincident with increased levels of serum intact PTH. The patient was treated with high dose calcium infusion after an ineffective treatment with 1 alpha-hydroxyvitamin D3; serum calcium and phosphorus as well as intact PTH and alkaline phosphatase levels were normalized. Evaluation of phytohemagglutinin-activated lymphocytes derived from this patient revealed that 1,25-(OH)2D3 was unable to inhibit thymidine incooperation, a result that contrasts with the capacity of 1,25-(OH)2D3 to inhibit uptake into normal activated lymphocytes. 1,25-(OH)2D3 did not induce human osteocalcin promoter activity after transfection of this DNA linked to a reporter gene into patient cells. Cointroduction of a human vitamin D receptor (VDR) cDNA expression vector with the reporter plasmid, however, restored the hormone response. Evaluation of extracts from the patient cells for VDR DNA binding revealed a defect in DNA binding. Analysis of genomic DNA from the patient's cells by PCR confirmed the presence of a point mutation in exon 2 of the VDR. This exon directs synthesis of a portion of the DNA-binding domain of the receptor. We conclude that the genetic basis for 1,25-(OH)2D3 resistance in this kindred with VDR-positive HVDRR is due to a single base mutation in the VDR that leads to production of a receptor unable to interact appropriately with DNA.

Binding Sites↗

Inhaled furosemide prevents ultrasonically nebulized water bronchoconstriction in children with both atopic and nonatopic asthma.

To determine whether inhaled furosemide can modify the bronchoconstriction induced by ultrasonically nebulized distilled water (UNDW) in children with both atopic and nonatopic asthma, a single-blind, randomized, placebo-controlled study was undertaken. The UNDW inhalation challenge was performed in 21 asthmatic children (atopic, 14; nonatopic, 7; mean +/- SEM age, 11.5 +/- 0.5 years), who had a fall in FEV1 of at least 20 percent after distilled water inhalation. On separate days, these subjects underwent UNDW challenge test after inhalation of furosemide (10 mg/body square meters) or placebo (saline solution). Inhaled furosemide exerted a protective effect against bronchoconstriction induced by UNDW in children with both atopic and nonatopic asthma (p < 0.01, p < 0.05, respectively). These results indicate that the protective action of furosemide against UNDW-induced bronchoconstriction may be independent of its direct inhibitory effect on airway mast cell activation.

Administration, Inhalation↗

Relationship between serum levels of methylguanidine and glycemic control in IDDM children.

OBJECTIVE: To examine the serum levels of methylguanidine in IDDM children and compare them with markers for glycemic control. Reports have indicated that active oxygen, which damages various tissues, increases in diabetes mellitus. The increase of active oxygen is one of the risk factors for diabetic complications. The synthesis of methylguanidine, a metabolic product of guanidine, is mainly regulated by active oxygen. RESEARCH DESIGN AND METHODS: Forty-eight children with IDDM (mean age 13.3 yr) and 17 age-matched nondiabetic control subjects were studied. Diabetic children were divided into a well-controlled group (HbA1c < 8%, n = 24) and a poorly controlled group (HbA1c > 8%, n = 24). Serum concentrations of methylguanidine were measured by enzymatic assay. RESULTS: Levels of methylguanidine in the poorly controlled group (1.31 +/- 0.08 microM) were significantly higher than those in both the well-controlled group (0.85 +/- 0.08 microM) and the control group (0.59 +/- 0.11 microM), respectively (P < 0.01). Methylguanidine levels showed a positive correlation with the levels of HbA1c (P < 0.01) or fructosamine (P < 0.01). No significant correlations were noted between methylguanidine levels and age, sex, duration of diabetes, or insulin dose. CONCLUSIONS: Our data indicate that the levels of methylguanidine in IDDM children might be affected by glycemic control and that the determination of serum methylguanidine levels could be a useful test for evaluating the state of diabetic control.

Biomarkers↗

[Three cases of anaphylaxis by tannalbin].

We reported 3 cases of patients developed moderate to severe anaphylactic reaction induced by tannalbin as anti-diarrhoeic. Specific IgE-mediated hypersensitivity to tannalbin was demonstrated by history, prick skin test, RAST and Immunoblotting. We also certified that tannalbin is composed by tannic acid and casein using HPLC and SDS-PAGE.

Adult↗

Effect of maturation on histamine-induced airflow obstruction and airway microvascular leakage in guinea pig airways.

To study the effect of maturation on histamine-induced airflow obstruction and airway microvascular leakage, we measured concomitant changes in lung resistance (RL) and in extravasation of Evans Blue dye in the airways of anesthetized immature (aged 14 +/- 2 days) and adult guinea pigs (aged 60 +/- 12 days). RL was measured for 6 min after iv. histamine (0, 5, 15, 30 and 50 micrograms/kg). For comparison, responses after 1 microgram/kg substance P were also examined. After measurement of RL, microvascular leakage in trachea, main bronchi, and proximal and distal intrapulmonary airways was also examined in the same animal. Immature animals required a larger dose of histamine than adults to achieve a similar degree of maximal bronchoconstriction after histamine. In contrast, equal doses of histamine (15 and 30 micrograms/kg) induced a significantly greater extravasation of dye in immature airways in both proximal and distal intrapulmonary airways, although not in trachea or main bronchi. Substance P did not cause any age-related differences in dye extravasation at any airway level. These results suggest that i.v. histamine specifically causes a greater degree of airway microvascular leakage in peripheral airways but induces less smooth muscle contraction in the airways of immature guinea pigs than in the airways of adult animals.

Aging↗

A case of congenital leukemia with monosomy 7.

A case of congenital leukemia with monosomy 7 is reported. Immunological study of the blast cells using monoclonal antibodies was suggestive of both myelomegakaryocytic and T-lymphoblastic leukemia. Chromosomal analysis of the bone marrow cells showed monosomy 7. Chemotherapy was initiated with a combination of adriamycin, cytosine arabinoside, 6-mercaptopurine, and prednisolone. The patient obtained complete remission, which has been maintained for 4 years and 1 month. He receives no chemotherapy now. Our case shows that monosomy 7 in congenital leukemia is rare, but the presence of monosomy 7 in congenital leukemia does not necessarily indicate a poor prognosis.

Antineoplastic Combined Chemotherapy Protocols↗

T-independent polyclonal activation of B cells in vitro by immunoglobulin binding substance (IBS) from the granary weevil.

Experiments are described for T-independent polyclonal activation of B cells in vitro by the immunoglobulin binding substance (IBS) from the granary weevil. The affinity-chromatographically purified IBS was used. IBS is a heat-, alkali- and acid-stable glucopeptide which is characterized by non-specific immunoglobulin binding to the Fab fragment. The purified IBS consists of three polymer homologues whose molecular weights are 12-14,000, 25-30,000 and more than 150,000 Da. IBS did not stimulate DNA synthesis by murine T cells, macrophages or plasma cells whereas it did stimulate that by mature B cells without any help from T cells or macrophages. IBS also stimulated both in vitro IgG production by spleen cells and in vitro sensitization of spleen cells by sheep red cells (SRBC). IBS was found to stimulate DNA synthesis by B cells mediated by binding to surface immunoglobulins of B cells. IBS is thought to be a useful amplifier for inducing human hybridomas and a valuable tool for examining mature B cells, both diagnostically and experimentally.

Animals↗

Inhibition of vascular permeability factor production by ciclosporin in minimal change nephrotic syndrome.

In order to ascertain whether ciclosporin (Cs) has an inhibitory effect on the vascular permeability factor (VPF) production, various quantities of Cs were added to T lymphocyte cultures from 8 children with minimal change nephrotic syndrome (MCNS) and the VPF activity of culture supernatants was assayed. As a result of the addition of Cs, a dose-dependent inhibition of VPF production was seen. VPF production was inhibited by a level of between 100 and 250 ng/ml of Cs in vitro. The reduction of proteinuria by Cs in MCNS might be due to the inhibition of VPF production.

Animals↗

Digoxin-like immunoreactive substance in urine of patients with mucocutaneous lymph node syndrome (MCLS).

Levels of digoxin-like immunoreactive substance (DLIS) and dehydroepiandrosterone sulfate (DHEA) in urine from patients with mucocutaneous lymph node syndrome (MCLS) were measured by radioimmunoassay. Because DLIS of stored samples was often below the level of detection by conventional immunoassay, the authors used 80% ammonium sulfate and extraction with phosphate buffer and then 80% hot ethanol. To study the origin of raised levels of DLIS in urine, the synthesis of DLIS by cultured human umbilical vein endothelial cells (HUVEC) was tested in vitro. The correlation between DLIS and DHEA levels was not significant. Mean levels of urinary DLIS corrected for creatinine in the patients with MCLS were significantly higher than in both normal and diseased controls. The culture medium of HUVEC was found to contain DLIS activity. These results show that MCLS should be added to the clinical states associated with an increased urinary concentration of DLIS and that the endothelial cells are one source of DLIS in man.

Blood Proteins↗

Developmental changes in gastric mucus gel thickness: responsiveness to 16,16-dimethyl prostaglandin E2 and mucosal protection in the rat.

The gastric mucosa of newborn rats is sensitive to the damaging effects of acid and ethanol. We measured gastric mucus gel thickness in newborn, suckling, and weaned rats by inversion microscopic observation. The thickness in newborn rats was 52.2 +/- 6.7 microns and increased with age, reaching 96.8 +/- 5.6 microns in 8-wk-old rats (p less than 0.001). Oral administration of 16,16-dimethyl prostaglandin E2 at concentrations of 10 and 100 micrograms/kg body weight increased mucus thickness in 8-wk-old rats but had no effect in 1-wk-old rats. We also assessed the effect of 16,16-dimethyl prostaglandin E2 on the prevention of gastric mucosal damage induced by ethanol. Oral 16,16-dimethyl prostaglandin E2 reduced damage in 8-wk-old rats, but there was no effect in 1-wk-old rats. These data suggest that the susceptibility of newborn rats to gastric mucosal injury may be related to the relative thinness of the gastric mucus gel layer and the failure of prostaglandins to increase the mucus gel layer thickness.

16,16-Dimethylprostaglandin E2↗

Plasma theophylline concentrations and airway function in asthmatic children receiving standard and modified RTC therapy.

The effects of three different dosage schedules for sustained-release theophylline (Theolong) were investigated in children with asthma. With regimen II (unequal doses at 0800 h and 2000 h), the maximum plasma theophylline concentration following the evening dose was significantly higher than that following the morning dose, and also was larger than that following the evening dose with regimen I (equal doses at 0800 and 2000 h). With regimen III (equal doses at 0600 h and 2100 h), the mean theophylline concentration-time curve showed a single large peak at 1100 h, whereas with regimen I, there were two peaks at 2300 and at 1400 h. Knowledge that a change of the dosage schedule can affect the pharmacokinetics of theophylline in this way should aid physicians in its safe and effective use.

Asthma↗

Erythroleukemia in a child associated with monosomy 7.

A case of erythroleukemia (EL) associated with monosomy 7 is reported. The EL was diagnosed 20 months after the initial diagnosis of monosomy 7 was made. An immunologic study of the blast cells using a monoclonal antibody was positive for glycophorin A, which suggested that they were of erythroid origin; this was confirmed by electron microscopy. Chemotherapy was started with low dose cytarabine. However, the patient had severe bone marrow suppression and died of pneumonia. Our case shows that monosomy 7 is an abnormality of the pluripotential stem cells, including erythroid cells, that resulted in a true erythroid neoplasm.

Child, Preschool↗

The role of the accessory pancreatic duct of Santorini in pancreatic drainage in children (with emphasis on choledochal cyst patients).

Pancreatic drainage patterns have been studied by endoscopic retrograde cholangiopancreatography (ERCP) in four children with choledochal cyst (CC). The first two had mild or chemical pancreatitis; the third had a history of recurrent cholangitis and was diagnosed as chronic pancreatitis. The fourth manifested with severe, acute pancreatitis. All children were found to have an impaired flow through the papilla of Vater. In the first three cases, the duct of Santorini (DS) seemed to play an important role in the pancreatic drainage. In the fourth case, however, the duct was found to be absent. ERCP findings in additional eleven children without CC also were reviewed, and in this group the DS did not seem to play any significant role in pancreatic drainage. These results indicate that in children with common bile duct (CBD) anomalies, the DS may relieve the obstruction and ameliorate the pancreatitis.

Acute Disease↗

Oral neurotensin increases gastrointestinal transit in suckling rats.

Several neuropeptides known to alter gastrointestinal motility are present in milk. We investigated the effect of gastric administration of neurotensin, bombesin, somatostatin, and vasoactive intestinal polypeptide on gastrointestinal motility in suckling rats. We gavage fed 7- to 10-day-old rats with a meal consisting of 10 microliters/g of body weight of 0.9% NaCl with 51Cr tracer and one of the peptides (0, 0.1, 10, and 1,000 ng/ml). We estimated the rates of gastric emptying and the small intestinal transit from the distribution of the radioactivity in the gut. Approximately one-half of the counts emptied from the stomach in 15 min. Both gastric emptying and small intestinal transit were time dependent and were accelerated by metoclopramide and inhibited by butylscopolamine. Neurotensin 1 micrograms/ml accelerated the gastric emptying by 35% (p less than 0.02). Small intestinal transit was also accelerated (p less than 0.05). The other neuropeptides had no effect on gastric emptying and small intestinal transit. Neurotensin did not change either the gastric emptying or small intestinal transit in weaned rats, 40-50 days old, studied in the same manner. These data suggest that the intraluminal administration of neurotensin may increase gastrointestinal motility in suckling animals.

Administration, Oral↗

A prefecture-wide survey of mumps meningitis associated with measles, mumps and rubella vaccine.

A survey of untoward reactions, especially central nervous system reactions, after the administration of a newly introduced measles, mumps and rubella (MMR) vaccine in Gunma Prefecture, Japan, was initiated soon after 4 patients were hospitalized for aseptic meningitis. Thirty-five, 6 and 2 children developed meningitis, convulsive disorders and parotitis, respectively, within 2 months after MMR vaccination during the 8-month period extending from April to November, 1989. The time lag between MMR vaccination and meningitis ranged from 14 to 28 days in the 35 cases of meningitis. Mumps virus, isolated from the cerebrospinal fluid in 13 patients with aseptic meningitis, was characterized by determination of the nucleotide sequences of the P gene as mumps vaccine strain. The incidence of aseptic meningitis with positive mumps vaccine virus was estimated to be 0.11% (0.3% as a whole) during the 8 months from April to November and increased to 0.3% (0.7% as a whole) in September and October. We conclude that the incidence of aseptic meningitis after MMR vaccination seems to be higher than that reported previously.

Adolescent↗