Shigeru Uemura

Revision of diagnostic guidelines for Kawasaki disease (the 5th revised edition)

Abstract  Diagnostic guidelines for Kawasaki Disease was revised to meet the present situation in 2002. This issue intends to explain new guidelines and their backgrounds. Major alterations are interpretation of cases with 4 or fewer febrile days shortened by early intravenous immunoglobulin treatment, and the clinical importance of atypical (incomplete, or suspected) cases.

Effects of immunoglobulin and gamma-interferon on the production of tumour necrosis factor-α and interleukin-1β by peripheral blood monocytes in the acute phase of Kawasaki disease

AbstractIn order to study the in vitro effects of intact immunoglobulin (Ig) and gamma-interferon (INF-γ) in patients with Kawasaki disease, the production of tumour necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) was measured in peripheral blood monocytes (PBM) both before and after intravenous immunoglobulin (IVIG) therapy. Spontaneous production of TNF-α and IL-1β both before and after IVIG therapy was significantly higher than in healthy controls. Intact Ig enhanced in vitro the production of TNF-α and IL-1β both before and after IVIG therapy approximately 3–4 times as compared to the spontaneous production. INF-γ did not affect the production of the two cytokines. Ig enhanced IL-1β mRNA expression in PBM of KD by 3–8 times more than that of spontaneous production.ConclusionThese results suggest that: (1) the mechanism of action of IVIG therapy in KD is not to cut down the production of inflammatory cytokines such as TNF-α and IL-1β andf that (2) the changes of these cytokine levels may be related to the clinical effectiveness of high dose IVIG.

Dilatation of the Ductus Arteriosus by Prostaglandins and Prostaglandin's Precursors

Summary: We studied the effects of prostaglandins and their precursors in animal models. Rabbit ductus arteriosus constricted rapidly after delivery. PGE1, PDE2, and arachidonic acid injected SC dilated the ductus over 60 min. Orogastrically administered PGE2 dilated the ductus for 3 hr. PGF2, and arachidonic acid showed weak ductus-dilating effects. Response of the ductus to PGE1 was most prominent in the first hr after birth. Pretreatment with indomethacin blocked the ductus-dilating effect of arachidonic acid.Speculation: Ductus-dilating effect of SC injected arachidonic acid present further support for the presumed role of the prostaglandins in maintenance of patency of the ductus arteriosus in infants with prematurity or severe congenital heart disease.The mechanism of age-related responsiveness of the ductus arteriosus to PGE1 and can be studied in animal model, and this approach may provide additional understanding and suggest new methods of management of the ductus arteriosus which is unresponsive to current medical manipulation.

The effect of glutamate on hypoxic newborn rabbit heart

Effects of glutamate on myocardial mechanical function and energy metabolism during 120 min of hypoxia and subsequent reoxygenation were studied in the isolated arterially perfused newborn and adult rabbit hearts. The muscle was perfused with a Krebs-Henseleit (KH) solution or KH solution which contained 1 mM glutamate. Glutamate attenuated the effects of hypoxia on mechanical function and tissue ATP concentration, and enhanced the recovery of mechanical function and tissue ATP during reoxygenation. During hypoxia, glutamate increased tissue succinate and GTP with no change in total lactate and pyruvate production. Trace studies using 14C-glutamate and the tissue homogenate showed that hypoxia increased tissue succinate and inhibited TCA cycle. Additional glutamate produced more CO2 and TCA intermediates in both oxygenated and hypoxic mediums. These data indicate that glutamate increased the rate of ATP production in the hypoxic and reoxygenated heart. This study shows that the improvement of mechanical function and ATP formation in the hypoxic myocardium by glutamate was due to an increase in both oxidative phosphorylation and substrate level phosphorylation. The effect of glutamate on the ATP and GTP production in the newborn heart was not different from the adult.

Nitric oxide may trigger lactation in humans

OBJECTIVE To determine whether nitric oxide is synthesized in the breast and plays a role in lactation. DESIGN Concentrations of biopterin, neopterin, and the total concentration of nitrite plus nitrate, a marker for nitric oxide generation were measured in 242 samples of breast milk obtained from 39 women during postpartum days 1 to 30. The total concentration of nitrite plus nitrate was measured in 17 sets of breast milk and serum obtained from 17 women on postpartum day 4 or 5. RESULTS (1) The total concentration of nitrite plus nitrate rose and peaked just before an increase in the volume of milk secreted was observed. (2) The total concentration of nitrite plus nitrate in breast milk was not correlated with that in the serum. (3) High levels of neopterin and biopterin were found in breast milk. (4) The volume of breast milk on day 5 was correlated with the total concentration of nitrite plus nitrate observed in breast milk on days 1 to 3. (5) The total concentration of nitrite plus nitrate in the breast milk of the high secretors significantly exceeded that seen in the low secretors. CONCLUSIONS We suggest that nitric oxide is synthesized in the breast and may trigger lactation in humans.

The Presence of Nitric Oxide Synthase in the Mammary Glands of Lactating Rats

Our objective was to show the presence of nitric oxide synthase (NOS) in the mammary glands of lactating rats and to determine the role that nitric oxide plays in lactation of humans. We used the nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase reaction and immunostaining on fresh frozen breast tissue obtained from lactating Wistar rats (13-18 wk old, 320-380 g, 3-4 d after parturition, first pregnancy). The breast tissues positive for NADPH diaphorase staining were the mammary gland, muscle, sebaceous gland, epidermis, and endothelium of the lactiferous ducts and blood vessels. These findings corresponded to tissues that were NOS-immunoreactive. The NOS detected in the mammary glands was the constitutive NOS. The finding of positive anti-NOS immunoreactivity and of positive NADPH diaphorase activity in the cells of the rat mammary glands leads us to conclude that nitric oxide is synthesized in mammary glands of rats. The high nitric oxide activity in the human breast was previously reported by measuring the total concentration of nitrite plus nitrate, biopterin, and neopterin in human milk. These results suggest that nitric oxide plays a role in the secretion of human breast milk.

Inverted left atrial appendage: an unusual complication in cardiac surgery

Two patients with an inverted left atrial appendage after cardiac surgery were presented. Magnetic resonance imaging is one of the useful methods to establish an accurate diagnosis of this complication. In 1 patient, it repaired spontaneously without surgical intervention.

Inotropic effects of prostaglandin D2 and E1 on the newborn rabbit heart.

ABSTRACT: This study determines the inotropic effects of prostaglandin D2 (PGD2) and prostaglandin E1 (PGE1) in the isolated, arterial perfused newborn (NB) and adult (A) rabbit heart.Significant positive inotropism of PGD2 was observed at all concentrations studied (1 × 10-17 to 1 × 10-7 M) in the two age groups; the effect in the NB was significantly greater (p < 0.05) than that in the A at PGD2 concentrations higher than 1 × 10-17 M. Significant positive inotropism of PGE1 was observed at PGE1 concentrations higher than 1 × 10-8 M in the NB, and only at 1 × 10-6 M in the A.In the NB, the relaxation parameters [1/2ART and the ratio of +dT/dt (max) to -dT/dt (max)] decreased to 80% of control after PGE1 infusion, but not after PGD2 infusion. In contrast, relaxation parameters in the A were not different from control.Propranolol (1 × 10-6 M) did not alter the positive inotropic action of PGD2 and PGE1 in the NB. These data indicate that: 1) the positive inotropic effects of PGD2 and PGE1 in NB are greater than that in the A, 2) PGE1 and not PGD2, enhances myocardial relaxation only in the NB,3) the contractile effects of PGD2 and PGE1 are not mediated by β-receptors.

Midterm results after ventricular septation for double-inlet left ventricle in early infancy.

We performed ventricular septation for a 40-day-old boy with double-inlet left ventricle and discordant ventriculoarterial connection but without pulmonary stenosis. Postoperative cardiac function is satisfactory, with no evidence of pulmonary hypertension or subaortic stenosis. Nine years after the operation, the patient has an active life, is free from symptoms, and requires no medication. He may be the first patient to survive ventricular septation for double-inlet left ventricle in early infancy.

Myocardial excitation-contraction coupling in the fetus of alloxan-diabetic rabbit.

ABSTRACT: This study was conducted to investigate myocardial excitation-contraction coupling in the fetus of the diabetic rabbit (FDM). On day 14 of gestation, diabetes was induced in pregnant rabbits by alloxan injection. On day 28 of gestation, mechanical function of the fetal myocardium was determined in the isolated arterially perfused heart preparation. At 1.5 mM [Ca2+]o (control), the force of myocardial contraction in FDM was not significantly dfferent from that in the control fetus. At higher [Ca2+]o, developed tension and maximal rate of tension development [+dT/dt (max)] in FDM were significantly greater than in the control fetus. High [Ca2+]o caused significant increases in resting tension and half-relaxation time (toxic effects) in the control fetus, but not in FDM. Perfusion with lanthanum (known to displace sarcolemma-bound Ca2+ and block sarcolemmal Na-Ca exchange) decreased developed tension and +dT/dt (max) and increased resting tension and these effects in FDM were significantly less than in the control fetus. Perfusion with manganese (known to displace Ca2+ from intracellular sites) also decreased developed tension and +dT/dt (max) and increased resting tension, and these effects were similar in the two groups. The myofibrillar ATPase activities at various calcium concentrations were not different between the two groups. The rates of Ca2+ uptake by mitochondria and sarcoplasmic reticulum were similar in the two groups. These data suggest that in FDM the inotropic effect of Ca2+ is greater and the toxic effect of Ca2+ is less than in the control fetus. This difference may be due, at least in part, to a sarcolemmal alteration induced by the maternal diabetes.