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Biomedical subjects

A Okuno

Publications and source records attributed to A Okuno.

At least 55 records · Page 3Linked to original sources
PubMed1998

Inhaled nitric oxide therapy via nasopharyngeal tube in an infant with end-stage pulmonary hypertension.

The delivery of nitric oxide (NO) via a nasopharyngeal tube is an alternative to endotracheal intubation. A male infant with end-stage pulmonary hypertension (PH) due to a severe hypoplastic lung developed a PH crisis on day 145 and received NO inhalation via a nasopharyngeal tube. Clinical improvement was maintained for 7 days with 18-22 ppm NO inhalation. The patient remained in close physical contact with his parents without the use of sedation. Blood methemoglobin levels remained below 1%. The environmental NO levels were less than 0.06 ppm and NO2 less than 0.3 ppm throughout the treatment, well within the safety margin. On day 152, the patient succumbed to hypoxemia and heart failure. The use of a nasopharyngeal NO delivery system without sedation, as an alternative to endotracheal intubation with sedation, was a practical method in treating a patient with PH while maintaining a certain quality of life for the patient and the family.

Administration, Inhalation↗
PubMed1998

Descriptive epidemiology of IDDM in Hokkaido, Japan: the Childhood IDDM Hokkaido Registry.

OBJECTIVE: To identify the incidence of IDDM with regard to sex, age, family history of diabetes, season, and 5-year period of childhood IDDM among children ages 0-14 years from a population-based epidemiological study in Hokkaido, Japan, from 1973 to 1992. RESEARCH DESIGN AND METHODS: Registration of all new IDDM cases in Hokkaido was conducted by the Childhood IDDM Hokkaido Registry Study Group from 1973 to 1992. The cases were selected from among 1) patients who were admitted to the member hospitals of the study group, 2) patients who answered a questionnaire distributed to hospitals and diabetic clinics throughout Hokkaido, and 3) patients whose cases were recorded in free-treatment medical records of urban and rural districts. The case ascertainment rate was estimated to be 100%. Differences in incidence with regard to sex, age, family history of diabetes, season, and year period were analyzed by the Poisson regression analysis by GENMOD. RESULTS: During the 20-year period studied, 396 cases (181 boys, 215 girls) of abrupt-onset IDDM were registered. Statistically significant differences in annual incidence were found according to sex (female), age (8-14 years), history (having no diabetes in family), season (spring), and 5-year period. CONCLUSIONS: This is the first population-based, long-term epidemiological study of childhood IDDM from Japan. We observed a significantly higher annual incidence (per 100,000/year) of IDDM in female subjects (1.81), older age-groups (2.25 for 8-14 years), subjects with no family history of diabetes (1.26), diabetes onset in the spring (2.20), and an increased trend over the 20 years. In addition, the heterogeneity of IDDM among Japanese children needs to be elucidated.

Adolescent↗
PubMed1998

[Constitutively activating mutations in the luteinizing hormone receptor gene in cases of male-limited precocious puberty].

Familial male-limited precocious puberty(FMPP) is an autosomal dominant disorder characterized by marked elevation of serum testosterone despite low levels of gonadotropin. In 1993, a single point mutation, Asp578 to Gly(D578G), in the luteinizing hormone(LH) receptor gene was found in FMPP families. After discovery of the D578G mutation in the sixth transmembrane region of the LH receptor gene, seven other mutations in the fifth and sixth transmembrane regions, two mutations in the third intracellular loop and one mutation in the second transmembrane domain of the LH receptor have been found in the patients with familial and sporadic male-limited precocious puberty. These mutations caused constitutively elevated cAMP levels in transfected cells in vitro. These results suggested that Leydig cell activation and precocious puberty were caused by activating mutations of the LH receptor.

Cyclic AMP↗
PubMed1997

Clinical significance of cytokine measurement for detection of meningitis.

Levels of interleukin-6 and tumor necrosis factor alpha were measured in cerebrospinal fluids from patients with meningitis. Interleukin-6 was increased in aseptic and bacterial meningitis, whereas tumor necrosis factor alpha was increased only in bacterial meningitis. We concluded that measurement of cytokines in cerebrospinal fluid may be useful for the rapid diagnosis of meningitis.

Case-Control Studies↗
PubMed1997

Acute effect of troglitazone on glucose metabolism in the absence or presence of insulin in perfused rat hindlimb.

Troglitazone (CS-045) is a new type of antidiabetic agent that decreases plasma glucose by enhancing insulin action in insulin-resistant diabetic animals and non-insulin-dependent diabetes mellitus (NIDDM) patients. To examine the direct effect of troglitazone on glucose metabolism and insulin action in skeletal muscle, we infused troglitazone solution into perfused rat hindlimbs in the presence of 6 mmol/L glucose and in the absence or presence of insulin. In the absence of insulin, even 50 mumol/L troglitazone did not elicit glucose uptake. Troglitazone did increase lactate and pyruvate release at concentrations of 20 mumol/L and higher; however, it decreased the ratio of lactate to pyruvate (L/P ratio) and increased oxygen consumption at concentrations higher than 5 and 20 mumol/L, respectively. In hindlimb muscle, 20 mumol/L troglitazone decreased glycogen content without changing fructose 2,6-bisphosphate (F2,6P2) content in the absence of insulin. Insulin infusion with 250 microU/mL obtained half-maximal effects, causing a 2.8-fold increase in glucose uptake and a 1.5-fold increase in lactate and pyruvate release. When 20 mumol/L troglitazone was infused for 30 minutes together with 250 microU/mL insulin, insulin-induced glucose uptake significantly increased 30 minutes after troglitazone infusion, and this increase was further augmented after withdrawal of troglitazone. In insulin plus troglitazone infusion at 30 minutes after troglitazone removal, glycogen content in hindlimb muscle was significantly decreased compared with that obtained with insulin infusion alone. In summary, in the absence of insulin, troglitazone does not elicit glucose uptake, but causes an increase in glycolysis accompanied by a decrease in muscle glycogen content and L/P ratio and an increase in oxygen consumption. In the presence of insulin, troglitazone increases insulin-induced glucose uptake, and this increase is further augmented after troglitazone removal. Addition of troglitazone to insulin infusion decreased the glycogen content in hindlimb muscle. This decrease in muscle glycogen content may trigger an enhancement of insulin-induced glucose uptake similar to that observed during muscle contraction or epinephrine treatment.

Animals↗
PubMed1997

A prospective study of prognostic value of type IV collagenase activity in colorectal cancer tissue.

The purpose of this prospective study was to evaluate the prognostic value of the type IV collagenase (IVase) activity in colorectal cancer tissue on disease-free and overall survival in 31 colorectal cancer patients. The clinicopathologic factors studied for prognostic value were age, tumor location, tumor differentiation, preoperative serum levels of carcinoembryonic antigen, Dukes' stage, and IVase activity in colorectal cancer tissue. IVase activities in colorectal cancer tissue were significantly higher in the group of patients with recurrences than in the group without recurrences (P = 0.019). Patients with high IVase activity in colorectal cancer tissue had a significantly shorter disease-free survival (P = 0.0016) and overall survival (P = 0.022) time than those with low IVase activity. Univariate and multivariate analysis showed that significant prognostic factors for disease-free survival were Dukes' stage (P = 0.029, P = 0.046, respectively) and IVase activity status (P = 0.0016, P = 0.0026, respectively). With respect to overall survival, only IVase activity status provided significant predictive value in multivariate analysis (P = 0.041). This prospective study suggests that IVase activity is a valuable prognostic factor in colorectal cancer patients.

Adult↗
PubMed1997

Atypical Epstein-Barr virus infection during and after intermittent FK506 therapy.

Atypical Epstein-Barr virus (EBV) infection developed in a patient under intermittent administration of FK506 (one dose in 10 days) after living-related liver transplantation. The clinical course was similar to severe chronic active EBV infection syndrome (SCAEBV), which is characterized by extremely high titers of antibody to EBV antigens. The clinical symptoms improved without graft rejection even after the cessation of FK506; however, the titers of antibody to EBV antigens remained at high levels. It was considered that: (i) even intermittent use of FK506 could influence the immune response, which then induced atypical EBV infection similar to SCAEBV; and (ii) the impaired immune response, especially to EBV antigens, remained after complete cessation of FK506.

Herpesviridae Infections↗
PubMed1997

Effect of hypoxia on amniotic fluid erythropoietin levels in fetal rats.

Erythropoietin (EPO) levels in amniotic fluid and serum were measured in hypoxic (fraction of inspired oxygen, FiO2, 0.09) and posthypoxic (following a 24-hour period of hypoxia, FiO2 0.09) fetal rats on day 21 of gestation. Each of the study groups comprised 12-20 fetuses. Each of the control groups consisted of 21 or 22 fetuses. Fetal serum EPO levels at 3, 6, 9, 12, and 24 h of hypoxia were significantly higher than the control level. Amniotic fluid EPO levels at 9, 12, and 24 h of hypoxia were also significantly increased compared to the control level. Fetal serum EPO levels returned to baseline during the 12- to 48-hour period after hypoxia. During the 0- to 48-hour posthypoxic period, amniotic fluid EPO levels were significantly higher than the control level. These data demonstrate that rates of appearance and turnover of amniotic fluid EPO are different from those of fetal serum EPO.

Amniotic Fluid↗
PubMed1997

Phe576 plays an important role in the secondary structure and intracellular signaling of the human luteinizing hormone/chorionic gonadotropin receptor.

Recent studies have identified multiple activating mutations in the sixth transmembrane domain of LH/chorionic gonadotropin receptor (LH/CGR) in patients with male-limited precocious puberty. Computer analysis suggested that these mutations had an effect on the secondary structure of the third cytoplasmic loop and sixth transmembrane domain, and that Phe576 was a critical conformational bridging residue between these regions that might be important for receptor activity. We made four amino acid substitutions of the Phe576 (F576I, F576G, F576Y, F576E) in the LH/CG receptor to analyze its functional role. Computer analysis of secondary structure predicted that the F576E mutant changed the secondary structure to a totally helical conformation in the region of the third intracellular and sixth transmembrane domain. In contrast, the F576G, F576I, and F576Y mutants were predicted to change the helical conformation in the region to an extended conformation. In expression studies, mutations of Phe576 produced functional changes in cAMP and inositol phosphate (IP) signaling, and human CG (hCG) binding. Mutations predicted to cause an extended conformation exhibited two functional patterns: first, constitutively activating in cAMP signaling without changes in IP signaling or hCG binding (F576I and F576G), and second, constitutively activating in cAMP signaling with decreased hCG-induced cAMP and IP signaling and with both higher affinity and lower capacity of hCG binding (F576Y). The mutation predicted to cause a totally helical conformation resulted in no cAMP response and a minimal IP response to hCG stimulation, with negligible hCG binding (F576E). These data suggest that the common change induced by the F576I, F576G, and F576Y mutations to an extended conformation on the third cytoplasmic loop and sixth transmembrane domain of the LH/CGR results in increased Gs coupling and activation of adenylyl cyclase. The F576Y mutation appears to have an additional effect, beyond a modification in receptor conformation, that leads to higher affinity and lower capacity of hCG binding, as well as altered Gq coupling and phospholipase C activation. The F576E mutation has a distinct and different impact on receptor conformation, which leads to negligible hCG binding and minimal function; however, the F576E mutation may provide a clue to understanding the receptor mutations that result in loss of function and pseudohermaphroditism. We conclude that Phe576 plays an important role in the human LH/CGR with respect to receptor conformation, Gs coupling, and cAMP signaling consistent with predictions from mutations associated with male-limited precocious puberty.

Amino Acid Sequence↗
PubMed1996

A case of male-limited precocious puberty caused by a point mutation in the second transmembrane domain of the luteinizing hormone choriogonadotropin receptor gene.

We describe a Japanese patient with male-limited precocious puberty who has a heterozygous thymine to cytosine (T to C) transition at nucleotide 1193; the mutation encodes a methionine to threonine substitution in residue 398 (M398T) of transmembrane helix 2 of the luteinizing hormone/choriogonadotropin receptor. Transfected into COS-7 cells, M398T exhibited constitutively high basal cAMP levels but retained an agonist-induced cAMP response. The constitutively higher cAMP levels caused by M398T are consistent with Leydig cell activation and precocious puberty in the patient. By comparison to wild type receptor, M398T transfectants have significantly lower agonist-induced inositol phosphate (IP) levels at > 10(-10) M hCG concentrations and a higher apparent affinity for binding hCG. These data suggest that the M398T substitution alters Gq coupling and phospholipase-C activation, as well as Gs, coupling and adenylyl cyclase activity, and changes the conformation of the extracellular domain of the receptor.

Amino Acid Sequence↗
PubMed1996

Moyamoya disease with precocious puberty and pustular psoriasis.

An 8-year-old girl suffering from precocious puberty and pustular psoriasis with moyamoya disease is described. The possibilities of a causal relationship between precocious puberty and moyamoya disease are discussed. The relevance of the patient's earlier upper respiratory tract infections to the pustular psoriasis and moyamoya disease is also considered.

Child↗
PubMed1996

Developmental changes in the noradrenergic innervations of spinal motoneurons in neonatal rats.

Developmental changes in the noradrenergic innervations of spinal motoneurons in both the cervical and lumbar cords were studied in neonatal rats. The labeling of motoneurons was done using choleratoxin B subunit as a retrograde neurotracer. The noradrenergic fibers were detected by immunohistochemistry for tyrosine hydroxylase. At postnatal day 1, tyrosine hydroxylase immunoreactive fibers were evident in the entire ventral horn, including the triceps brachii motoneuron pools at the cervical level. In contrast, they were observed only in that portion of the ventral horn medial to the quadriceps femoris motoneuron pools at the lumbar level. Subsequently, tyrosine hydroxylase immunoreactive fibers increased at both levels, and they were distributed in most of the gray matter at postnatal day 14. At this age, the distribution pattern of tyrosine hydroxylase immunoreactive fibers in the lumbar level was almost identical to that of the cervical level. The number of closely apposed tyrosine hydroxylase immunoreactive varicosities on motoneurons (close appositions) increased continuously from postnatal day 1 to 14 at both the cervical and lumbar levels. At postnatal day 1, triceps brachii motoneurons had more close appositions than quadriceps femoris motoneurons in number and, after postnatal day 7, there was no difference in the number of close appositions between triceps brachii motoneurons and quadriceps femoris motoneurons. Based on these results, we discuss the significance of monoaminergic influences on the postnatal development of spinal motoneurons and of motor behavior with a rostrocaudal gradient.

Adrenergic Fibers↗
PubMed1996

Ultralente insulin treatment of transient neonatal diabetes mellitus.

In an infant with transient neonatal diabetes mellitus, control of the blood glucose concentration was attained with ultralente insulin treatment, without any episodes of hypoglycemia. We recommend subcutaneous injection of ultralente insulin, rather than lente or isophane (NPH) insulin, to avoid hypoglycemia during the treatment of transient neonatal diabetes mellitus.

Diabetes Mellitus↗