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The copper(I)-catalyzed carboxylation reaction of aryl- and alkenylboronic esters proceeded smoothly under CO(2) to give the corresponding carboxylic acid in good yield. This reaction showed wide generality with higher functional group tolerance compared to the corresponding Rh(I)-catalyzed reaction.

Synthesis of naphthalyne-Co2(CO)6 complexes, the first example of the aryne-Co2(CO)6 complex, was achieved via cyclization of acyclic alkyne-Co2(CO)6 complex precursors containing an allylsilane and an aldehyde moiety followed by dehydration. Unique reactivities of the complexes toward oxygen to give carboxylic acid derivatives and toward alkynes to give cyclopentadienone derivatives were also disclosed.

Pentalogy of Cantrell is a rare congenital defect associated with five ventral midline anomalies and high mortality. An obstetric sonogram revealed a fetus with a body wall defect suggesting a diagnosis of this condition. Soon after birth, the infant underwent a closure of the upper abdominal wall defect followed by the successful repair of double-outlet right ventricle and pulmonary valve stenosis at the age of 5 months. The patient is currently alive and well 3.5 years after surgery. It is concluded that a deliberate therapeutic strategy based on the intrauterine diagnosis may alter the natural history of this devastating disorder.

Many epidemiologic studies have disclosed that restricted fetal growth has been associated with an increased risk of insulin resistance in adulthood. We studied the relationship of intracellular magnesium [Mg2+]i in cord blood platelets to adipocytokine and birth size. The subjects were 20 infants with small for gestational age (SGA) and 45 infants with appropriate for gestational age (AGA). By using a fluorescent probe, we examined [Mg2+]i of platelets in the cord blood. Cord plasma insulin, IGF-I, ghrelin, adiponectin, plasminogen activator inhibitor-1 (PAI-1), and leptin levels were determined with the use of ELISA. Mean [Mg2+]i was lower in the SGA than in the AGA groups (p < 0.001). Adiponectin and IGF-I were also lower in the SGA than in the AGA, whereas PAI-1 was higher in the SGA. [Mg2+]i was significantly correlated with birth weight, birth length, and adiponectin. Birth weight was also correlated with cord plasma IGF-I, adiponectin, and leptin. Quantitative insulin sensitivity check index (QUICKI) was lower in the SGA group than in the AGA group. [Mg]i and adiponectin were correlated with QUICKI in all subjects. [Mg]i, as well as leptin and IGF-I, reflect the extent of fetal growth. Decreased [Mg2+]i may be involved in the underlying processes to insulin resistance.

[structure: see text]. A novel method for the preparation of hydroxy carboxylic acid derivatives has been developed by O2-oxidation of pi-allylnickel intermediates generated by Ni(0)-mediated coupling of 1,2-dienes with CO2.

In this paper, we report the usefulness of magnetic resonance cholangiopancreatography (MRCP) in excluding biliary atresia (BA) as the cause of neonatal cholestasis. MRCP with a 1.5-T magnetic resonance (MR) imaging unit was performed on four jaundiced neonates and infants aged from 38 days to 106 days. The diagnosis of BA (n=2) was confirmed with surgery, liver biopsy and surgical cholangiography. Diagnosis of neonatal hepatitis (NH, n=2) was confirmed with clinical follow-up until jaundice resolved, while one of them was diagnosed with surgical cholangiography. In all discoloured acholic stools, increased direct bilirubin (4.4-11.3 mg/dl) with positive lipoprotein X prompted technetium 99mTc disofenin scanning, which showed no excretion. Computed tomography (CT) showed a gallbladder in one with hepatitis but no intrahepatic bile duct in two with BA. The Kasai operation was performed in two patients with BA. In two patients with BA, neither the common bile duct nor the common hepatic ducts were visible at MRCP. In two patients with NH, MRCP clearly depicted both the common hepatic and the common bile ducts. MRCP was accurate in excluding BA as the cause of neonatal cholestasis, while 99mTc disofenin cholescintigraphic findings were false-positive in two patients with non-obstructive cholestasis. We conclude that MRCP can be used to depict the major biliary structures of neonates and small infants and to exclude BA as the cause of neonatal cholestasis by allowing visualisation of the biliary tract.

Unlabelled: We report a patient with human herpesvirus-6 (HHV-6) encephalitis diagnosed by diffusion-weighted magnetic resonance imaging (DW-MRI). A previously healthy 10-month-old girl developed acute encephalopathy. HHV-6 DNA was detected in her cerebrospinal fluid during the acute phase of the disease by polymerase chain reaction. The patient demonstrated cortical diffusion abnormalities in affected brain parenchyma, partially as the initial or most sensitive sign of encephalitis that could be detected not by conventional MRI but by DW-MRI. Serial imaging showed that the diffusion abnormality DW-MRI returned to normal after 45 days., Conclusion: DW-MRI may be a valuable tool for early detection and diagnosis of HHV-6 encephalitis and is more sensitive than conventional MRI to detect a subtle edematous change in the brain.

Citrin deficiency induces two clinical features; namely neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) and adult-onset type II citrullinemia. Hypercitrullinemia is the most characteristic feature, whereas there are non-citrullinemic individuals. Diagnosis of citrin deficiency is performed by genetic analysis, although the 12 known mutations in the alleles are not detected in about 15% of cases. Thus, we aimed to examine citrin protein in lymphocytes isolated from peripheral blood as an alternative diagnostic method. We examined 38 children having an episode of cholestatic liver dysfunction, 8 heterozygotes, and 11 healthy individuals. All subjects were evaluated for citrin protein by Western blotting and for the 12 known mutations by gene analysis. Citrin protein was detected in 15 of 38 children with cholestatic liver dysfunction. Fourteen of them were negative for 12 known mutations in both alleles, whereas one patient was found to have a known mutation in one allele. Citrin protein was absent in 23 of the 38 patients. Among these 23, gene analysis diagnosed citrin deficiency in 19, whereas 2 patients were later revealed to be NICCD with novel mutations. In the remaining 2 patients, who exhibit the clinical features of NICCD, a known mutation was detected in one allele but no mutation was identified in another allele. Citrin protein was also detected in the 8 heterozygotes and 11 healthy individuals. We disclosed that citrin was deficient in lymphocytes among patients with citrin deficiency. Analysis of citrin is useful to diagnose citrin deficiency even in patients without known mutations or hypercitrullinemia.

When the esters of arylboronic acids with 2,2-dimethylpropan-1,3-diol were treated with a catalytic amount of [Rh(OH)(cod)]2 in the presence of 1,3-bis(diphenylphosphino)propane and CsF in dioxane at 60 degrees C under carbon dioxide atmosphere, the benzoic acid derivatives were obtained in good yields. Reactions of alkenylboronic esters also proceeded under similar conditions to give alpha,beta-unsaturated carboxylic acids. As these boronic esters are now easily available through coupling or direct borylation reactions, this method would be a useful method for the preparation of various functionalized aryl- and alkenyl-carboxylic acids.

Intermolecular 1,5-dipolar cycloaddition reaction of tungsten-containing vinylazomethine ylide, generated from o-(alk-3-en-1-ynyl)phenylbenzaldimines and tungsten carbonyl complex, with ketene acetals proceeds efficiently to give azepino[1,2-a]indole derivatives in good yield. Formation of [5+2] or [3+2] cycloadducts can be controlled by an appropriate choice of dipolarophile.

Magnesium deficiency in pregnant women is frequently seen because of inadequate or low intake of magnesium. Magnesium deficiency during pregnancy can induce not only maternal and fetal nutritional problems, but also consequences that might last in offspring throughout life. Many epidemiological studies have shown that restricted fetal growth, i.e. intrauterine growth retardation (IUGR), is associated with an increased risk of insulin resistance in adult life. We previously postulated that the intracellular magnesium of cord blood platelets is lower in the small for gestational age group than in the appropriate for gestational age group, suggesting that intrauterine magnesium deficiency may result in IUGR. Taken together, intrauterine magnesium deficiency in the fetus may lead to or program the insulin resistance after birth. We hypothesize that intrauterine magnesium deficiency may induce a metabolic syndrome in later life. Prospective studies will further clarify whether infants with IUGR induced by magnesium deficiency are at higher risk for metabolic syndromes in childhood or adulthood.

[reaction: see text] Only 1-3 mol % of PtCl(2) or AuBr(3) was sufficient to promote generation and [3+2] cycloaddition of transition-metal-containing azomethine ylides derived from N-(o-alkynylphenyl)imines bearing an internal alkyne moiety. A highly efficient method for the preparation of synthetically useful tricyclic indole derivatives having a substituent at the 3-position of the indole nucleus was established by this method.

Unlabelled: We report the case of a 7-yr-old girl with Turner syndrome, ulcerative colitis (UC) and coarctation of the aorta. The diagnosis of Turner syndrome was made in early infancy (karyotype analysis 45, X). Growth hormone treatment was started at 3 yr and 2 mo of age. From the age of 4 yr and 5 mo, the patient suffered from persistent diarrhea with traces of blood and intermittent abdominal discomfort. As these symptoms gradually deteriorated, she was referred to our clinic at the age of 7 yr for further evaluation. Barium enema showed aphtha and loss of the fine network pattern in the descending colon and rectum. An endoscopic examination showed ulceration, edema, friability, and erythema beginning in the rectum and extending up to the splenic flexure of the descending colon. The histology of the descending colon area showed severe stromal infiltration of inflammatory cells. These endoscopic findings and the histological findings were consistent with UC. Thus, based on these findings, the patient was diagnosed as having UC. Mesalazine therapy was initiated at this time. The patient is currently being treated with mesalazine (1,000 mg/day) and abdominal symptoms and bloody diarrhea have disappeared. GH therapy was not interrupted during the therapy for UC. Retrospectively, growth hormone improved growth velocity (9 cm/year) during the first year of treatment, however from the age of 4 yr, growth velocity decreased (4-5 cm/yr) in spite of the GH treatment., Conclusion: Patients with Turner syndrome and gastrointestinal symptoms should be investigated for inflammatory bowel diseases. Growth velocity is useful for evaluating the presence of inflammatory bowel diseases and other systemic diseases.

Deficiency of citrin due to mutations of the SLC25A13 gene causes not only adult-onset type II citrullinemia, but also neonatal intrahepatic cholestasis. Neonatal intrahepatic cholestasis is a self-limiting condition and spontaneously disappears by 12 months of age without special treatment. The natural history of patients with SLC25A13 mutations is not clear. Two patients with infantile hepatic dysfunction were found to have a novel mutation of the SLC25A13 gene. DNA analyses of SLC25A13 disclosed that the first patient was a compound heterozygote for the Ex16+74&#95;IVS17-32del516 (del516-Ex16/IVS17) and IVS11+1G-->A mutations and the second one a homozygote for the del516-Ex16/IVS17 mutation. It is predicted that the 516-base pair deletion mutation leads to a frameshift from codons 556 to 564, a premature termination at codon 565, and a truncated form of the citrin protein (normal, 675 amino acids). The first patient had disseminated intravascular coagulation associated with hepatic dysfunction in the neonatal period. The other patient had persistent cholestatic jaundice and underwent an operation to rule out bile duct atresia. Without specific treatment, both patients had a favorable clinical course. In conclusion, citrin deficiency resulting from the mutation of SLC25A13 presented variant clinical courses, followed by hypercitrullinemia and intrahepatic cholestasis in infancy. The conditions in the patients were self-limiting and spontaneously disappeared.

Chronic magnesium deficiency in pregnant women is frequently seen because of inadequate or low intake of magnesium. Magnesium deficiency during pregnancy can induce not only maternal and fetal nutritional problem, but also pediatric consequences that might last throughout life. Many epidemiological studies have disclosed that restricted fetal growth, i.e., intrauterine growth retardation (IUGR) is associated with an increased risk of insulin resistance in adult life. We previously postulated that intracellular magnesium of cord blood platelets is lower in the small for gestational age than in the appropriate for gestational age group, suggesting chronic intrauterine magnesium deficiency may result in IUGR. Taken together, chronic intrauterine magnesium deficiency in the fetus may lead to or program the insulin resistance after birth. Prospective study whether the children born with magnesium induced IUGR are at high-risk for metabolic syndrome in childhood or adulthood is currently undertaken.

Unlabelled: We followed up a girl with primary aldosteronism for 8 y, which was diagnosed at 6 y of age when she was referred to us for evaluation of heart murmur and growth failure. The diagnosis of bilateral adrenal hyperplasia was made by selective adrenal venous sampling. Following potassium supplement, her retarded growth was corrected dramatically, and she attained a normal adult height. Puberty developed normally and menarche occurred at 12 y of age. Blood pressure was also controlled adequately. Myocardial hypertrophy associated with aortic damage was noted at 13 y of age. Chronic renal failure developed with proteinuria and enlarged renal cysts., Conclusion: Serum electrolytes should be included in the evaluation of children with impaired growth. Although primary aldosteronism is a rare occurrence in children, the condition appears to deserve special attention not only from the viewpoint of growth failure and hypokalaemia but from the occurrence of late organ damage to the kidney and heart.

Studies are described that reveal the steps of the anti-Markovnikov hydroamination of vinylarenes with alkylamines catalyzed by Ru(COD)(2-methylallyl)2, bis(diphenylphosphino)pentane, and TfOH. Treatment of the catalyst components with an excess of styrene under the catalytic reaction conditions afforded a new ruthenium eta6-styrene complex with an ancillary tridentate PCP ligand. This ruthenium complex was active as catalyst for the hydroamination of styrene with morpholine to give the anti-Markovnikov adduct as a single regioisomer in high yield. Studies of the reactivity of the eta6-styrene complex revealed two reactions that comprise a catalytic cycle for anti-Markovnikov hydroamination: nucleophilic addition of morpholine to the ruthenium eta6-styrene complex to afford a ruthenium eta6-(2-aminoethyl)benzene complex and arene exchange of the ruthenium eta6-(2-aminoethyl)benzene complex with styrene to regenerate the ruthenium eta6-styrene complex. The addition of morpholine and the exchange of arene occurred with comparable rates. These results strongly suggest that the ruthenium-catalyzed anti-Markovnikov addition of alkylamines to vinylarenes occurs by a new reaction mechanism for hydroamination involving nucleophilic attack on the eta6-vinylarene complex and exchange of the aminoalkylarene complex product with free vinylarene. This mechanism is a rare example of catalytic chemistry through pi-arene complexes. These mechanistic data were used to select derivatives of the DPPP ligand that improve the rates of the catalytic process.

Novel tungsten-containing carbonyl ylides 7, generated by the reaction of the o-alkynylphenyl carbonyl derivatives 1 with a catalytic amount of W(CO)(5)(thf), reacted with alkenes to give polycyclic compounds 5 through [3 + 2]-cycloaddition reaction followed by intramolecular C-H insertion of the produced nonstabilized carbene complex intermediates 8. In the presence of triethylsilane, these tungsten-containing carbene intermediates 8 were smoothly trapped intermolecularly by triethylsilane to give silicon-containing cycloadducts 17 with regeneration of the W(CO)(5) species. By this procedure, the scope of alkenes employable for this reaction was clarified. The presence of the tungsten-containing carbonyl ylide 7c was confirmed by direct observation of the mixture of o-ethynylphenyl ketone 1c and W(CO)(5)(thf-d(8)). Careful analysis of the intermediate by 2D NMR, along with the observation of the direct coupling with tungsten-183 employing the (13)C-labeled substrate, confirmed the structure of the ylide 7c. Examination using (E)- or (Z)- vinyl ether revealed that the [3 + 2]-cycloaddition reaction proceeded in a concerted manner and that the facial selectivity of the reaction differed considerably depending on the presence or absence of triethylsilane. These results clarified the reversible nature of this [3 + 2]-cycloaddition reaction.

Magnesium (Mg(2+)) has an important role in insulin action, and insulin stimulates Mg(2+) uptake in insulin-sensitive tissues. Impaired biologic responses to insulin are referred to as insulin resistance. Diabetic patients and obese subjects are reported to have intracellular magnesium ([Mg(2+)](i)) deficiency. Many epidemiologic studies have disclosed that restricted fetal growth has been associated with increased risk of insulin resistance in adult life. We studied the relationship of [Mg(2+)](i) in cord blood platelets to birth weight. The subjects were 19 infants who were small for gestational age (SGA) and 45 who were appropriate for gestational age (AGA). By using a fluorescent probe, mag-fura-2, we examined the basal and insulin-stimulated [Mg(2+)](i) of platelets in the cord blood. Cord plasma insulin-like growth factor-1 (IGF-1)and leptin levels were determined with the use of enzyme-linked immunosorbent assay (ELISA). Birth weight was correlated with cord plasma IGF-1 (P < .001) and leptin (P < .005). Mean basal [Mg(2+)](i), but not plasma Mg(2+), was lower in the SGA than in the AGA group (291 +/- 149 micromol/L v 468 +/- 132 micromol/L, P < .001). The basal [Mg(2+)](i) was significantly correlated with the birth weight (P < .001) as well as birth length (P < .001). At 60 seconds after stimulation with insulin, there was no significant difference in stimulated [Mg(2+)](i) between the SGA and AGA groups. Although the SGA group had low [Mg(2+)](i), the platelets had good potentiality to compensate for low [Mg(2+)](i). [Mg(2+)](i) reflects the extent of fetal growth. Decreased [Mg(2+)](i) in SGA might underlie the initial pathophysiologic events leading to insulin resistance.

Unlabelled: Kawasaki disease (KD) is an acute vasculitis of unknown aetiology with varied clinical manifestations. Although coronary arteritis is common in the course of KD, central nervous system involvement is rare. We report a case of KD in an infant who developed convulsions and apnoea during his illness associated with syndrome of inappropriate secretion of antidiuretic hormone (SIADH)., Conclusion: The possibility of severe hyponatraemia should be anticipated in children with KD. Infants with KD are at risk of SIADH and should be monitored closely for its development.

Unlabelled: Magnesium, the second most abundant intracellular divalent cation, is a cofactor of many enzymes involved in glucose metabolism. Magnesium has an important role in insulin action, and insulin stimulates magnesium uptake in insulin-sensitive tissues. Impaired biological responses to insulin is referred to as insulin resistance. This review was designed to reach a better understanding of the mechanism involved in the correlation between magnesium and insulin resistance. Intracellular magnesium concentration is low in type 2 diabetes mellitus and in hypertensive patients. In patients with type 2 diabetes an inverse association exists between the plasma magnesium and insulin resistance due to intracellular changes. The suppressed intracellular magnesium concentration may result in defective tyrosine kinase activity and modify insulin sensitivity by influencing receptor activity after binding or by influencing intracellular signaling and processing. Intracellular magnesium deficiency may affect the development of insulin resistance and alter the glucose entry into the cell., Conclusions: Magnesium is required for both proper glucose utilization and insulin signaling. Metabolic alterations in cellular magnesium, which may play the role of a second messenger for insulin action, contribute to insulin resistance.

[reaction: see text] A concise method for the preparation of 1-acyl-4-alkoxy- or 1-acyl-4-alkylsulfanylnaphthalenes has been developed by the reaction of o-ethynylbenzoates or benzothioates with vinyl ethers, in the presence of a catalytic amount of PtCl(2). It is proposed that the reaction proceeds through [3 + 2]-cycloaddition of the platinum-containing carbonyl ylides followed by 1,2-alkyl migration.

Background: Because of recent improvements in diagnostic procedures, many cases of congenital dilatation of the bile duct (CDBD) have been diagnosed in early life. To determine the mode of presentation and changes in diagnostic tools, medical records of 34 children (25 girls, nine boys) with CDBD who were treated between 1982 and 2000 were reviewed., Results: The age at presentation ranged from 0 to 16 years (median 4.9 +/- 0.7 years), with two patients being diagnosed using prenatal ultrasonography. Of the 32 patients diagnosed post-natally, 21 (66%) complained of abdominal pain. There were also 21 (66%) cases of vomiting. Sixteen patients (50%) experienced both these symptoms. Ten (31%) cases presented with jaundice and three (9%) presented with a palpable mass. Ultrasonography was used as a diagnostic tool in 29 cases (85%). The finding of a dilated common bile duct on abdominal ultrasonography was helpful for early diagnosis. Spiral computed tomography was also a useful and accurate imaging method for diagnosis. Anomalous pancreaticobiliary junction (PBJ) was demonstrated in 44% of patients with CDBD. Magnetic resonance cholangiopancreatography, which can be performed non-invasively, is useful for the diagnosis and pre-operative assessment of CDBD in children. The average length of time from presentation to diagnosis could be shortened from 46 days (1982-1988) to 13 days (1995-2000)., Conclusion: Recent improvements in diagnostic procedures make immediate, non-invasive diagnosis of CDBD and PBJ possible.

Magnesium (Mg(2+)), the second most abundant intracellular cation, is a critical cofactor in numerous enzymatic reactions. By using a fluorescent probe, mag-fura-2, we examined the basal levels and changes in intracellular Mg(2+)([Mg(2+)](i)) of platelets in diabetic and obese children. Under the basal condition, the platelet [Mg(2+)](i) of both type 1 and type 2 diabetes mellitus (DM) and the obesity groups was significantly lower than the values in the nondiabetic control group (377 +/- 62 micromol/L, 312 +/- 72 micromol/L, 373 +/- 35 micromol/L v 594 +/- 62 micromol/L, respectively, P <.05). [Mg(2+)](i) was increased after the stimulation with 100 microU/mL of insulin. After 60 seconds of insulin stimulation, the value of [Mg(2+)](i) was lower in the type 1 DM group compared with the control group (729 +/- 85 micromol/L v 1,078 +/- 67 micromol/L, P <.005). The increase in percentage over the resting [Mg(2+)](i) was higher in the type 2 DM group than in the stimulated control group (222% +/- 51% v 98% +/- 18 %, P <.05), although the stimulated [Mg(2+)](i) did not reach the level of the control group. The diabetic patients and obese subjects have [Mg(2+)](i) deficiency. In the type 2 DM and obese groups, platelets responded well to insulin. In children under insulin-resistant states, [Mg(2+)](i) decreases before the poor reactivity to insulin occurs in platelets. Decreased [Mg(2+)](i) might underlie the initial pathophysiologic events leading to insulin resistance and abnormality of platelet coagulation., (Copyright 2003 Elsevier, Inc. All rights reserved.)

Unlabelled: Transmesenteric hernia is a rare cause of small bowel obstruction and is seldom diagnosed preoperatively, partly because of unfamiliarity with this type of internal hernia. The clinical symptoms of internal hernia may be intermittent and nonspecific, making the diagnosis extremely difficult. We report two patients, 7- and 5-year-old girls, with mesenteric hernia of the ileum. Because of the difficulty of clinical diagnosis of internal hernia, imaging studies played a crucial role. We would like to stress the importance of plain radiological findings as diagnostic aids., Conclusion: a consistent intestinal gas imaging after some interval suggests the possibility of an internal hernia, especially accompanied with a circular or oval defect of the gas shadows in the middle of the abdomen. A serial abdominal X-ray study can be helpful in the diagnosis of internal hernia.

Treatment of N-(o-alkynylphenyl)imine derivatives with W(CO)(5)(L) induces the 5-endo-mode of cyclization of the imine nitrogen onto the electrophilically activated alkyne moiety to afford a novel reactive species, a metal-containing azomethine ylide. [3 + 2] cycloaddition of this ylide species with various electron-rich alkenes proceeds smoothly to give unstable carbene complexes, which in turn undergo 1,2-hydrogen-, alkyl-, and aryl-migration to afford in good yield 6-5-5 tricyclic indole skeletons having an alkyl or an aryl substituent at the 3-position of the indole nucleus.

In wild-type mice, 2-wk administration of losartan, an angiotensin (Ang) II type 1 (AT1) receptor antagonist, along with dietary sodium restriction, resulted in an elevation of plasma aldosterone greater than that seen with sodium restriction alone (2.75 +/- 0.35 vs. 1.38 +/- 0.16 ng/ml, P < 0.01). Plasma potassium increased in sodium-restricted, losartan-treated mice (6.0 +/- 0.2 mEq/liter), while potassium remained unchanged in mice with sodium restriction alone. To study the effect of Ang II on glomerulosa cells that may operate independently of plasma potassium in situ, we used chimeric mice made of cells with or without the intact AT1A gene (Agtr1a). When animals were fed a normal diet or chronically infused with Ang II, the aldosterone synthase mRNA was detectable only in Agtr1a+/+ but not Agtr1a-/- zona glomerulosa cells. After 2 wk of sodium restriction, plasma aldosterone increased (1.51 +/- 0.27 ng/ml) and potassium remained on average at 4.5 +/- 0.2 mEq/liter, with aldosterone synthase mRNA expressed intensively in Agtr1a+/+, but not detectable in Agtr1a-/- cells. Simultaneous sodium restriction and losartan treatment caused increases in plasma potassium (5.5 +/- 0.1 mEq/liter) and aldosterone (1.84 +/- 0.38 ng/ml), with both Agtr1a-/- and Agtr1a+/+ cells intensively expressing aldosterone synthase mRNA. Thus, aldosterone production is regulated by Ang II in the adrenal gland during chronic alterations in extracellular fluid volume when plasma potassium is maintained within the normal range. In the light of a previous observation that dietary potassium restriction superimposed on sodium restriction abolished secondary hyperaldosteronism in angiotensinogen null-mutant mice, the present findings demonstrate that when the renin-Ang system is compromised, plasma potassium acts as an effective alternative mechanism for the volume homeostasis through its capacity to induce hyperaldosteronism.

Recent studies suggest an association between Chlamydia pneumoniae infection and coronary artery disease (CAD). To examine this relationship in Japanese men, serum IgA and IgG antibodies to Chlamydia-specific lipopolysaccharide were measured by enzyme-linked immunosorbent assay in 507 patients with CAD and 200 age-matched controls. CAD patients were divided into (1) 269 patients with myocardial infarction (MI) and (2) 238 patients with chronic coronary heart disease (CCHD). Compared with the control group, the CAD group did not differ in the prevalences of both antibodies (IgA: 23.7 vs 18.0%, p=0.10; IgG: 52.7 vs 51.0%, p=0.6). The index of IgG antibody was not significantly different between CAD and control groups (median 1.19 vs 1.18, p=0.3), whereas the index of IgA antibody was significantly higher in CAD than control group (median 0.60 vs 0.46, p<0.0001). Compared with the control group, the MI group had a significantly higher prevalence of IgA antibody (28.6 vs 18.0%, p=0.007); however, there was no difference in the prevalence of IgG antibody (58.0 vs 51.0%, p=0.13). The CCHD group did not differ in the prevalences of both antibodies (IgA: 18.1 vs 18.0%, p=0.9; IgG: 45.6 vs 51.0%, p=0.2). After the adjustment for coronary risk factors, odds ratios (ORs) of seropositive antibodies for CAD were 1.59 [95% confidence interval (CI): 0.88-2.87, p=0.12] for IgA seropositivity and 0.92 (95%CI: 0.58-1.47, p=0.7) for IgG seropositivity in all cases. In the MI and control groups, ORs of seropositive antibodies for MI were 2.67 (95%CI: 1.32-5.38, p=0.007) for IgA seropositivity, and 1.36 (95%CI: 0.79-2.36, p=0.2) for IgG seropositivity. This study discovered that IgA antibody to Chlamydia was significantly associated with CAD, especially with MI, in Japanese Men and the findings suggest that chronic infection of Chlamydia may be linked to the pathogenesis of MI.

The gene-targeting technology allows complete and selective inactivation of a specific gene to study the consequence of total absence of the gene product. The availability of such null-mutant mice enables investigators to identify the biological function of the gene product in physiological or pathophysiological conditions. This technology, popularly known as "gene knockout," can also induce more subtle mutations at the targeted site of the genome.

We wished to determine the relationship between circulating levels of nitric oxide (NO) and cardiac index (CI) in children with congenital heart diseases. We measured the plasma levels of nitrate/nitrite (NO(x)), the stable end products of NO production as well as tumor necrosis factor-alpha (TNF-alpha), atrial natriuretic peptide (ANP), and brain natriuretic peptide in relation to various parameters determined simultaneously. The plasma NO(x) levels correlated negatively with CI (r = -0.541, p < 0.05). No correlation was observed between NO(x) and cardiac output. TNF-alpha correlated with NO(x) levels (r = 0.593, p < 0.005) but not with either CI or cardiac output. Plasma levels of ANP and TNF-alpha were higher in atrial septal defect than those in the control group (p < 0.001 and p < 0.05, respectively). Elevated plasma NO(x) could explain the increased basal release of endothelial NO due to high pulmonary blood flow. Plasma NO(x) correlate negatively with CI in young patients with left-to-right shunt congenital heart diseases.

On treatment of silyl enolates and an N,O-hemiacetal, derived from trifluoroacetaldehyde ethyl hemiacetal and p-anisidine, with GaCl(3) (0.2 equiv) and C(6)H(5)COCl (0.2 equiv) in propionitrile, Mannich-type reaction took place smoothly to afford beta-amino-beta-trifluoromethyl carbonyl compounds in high yields.

Free intracellular Mg2+([Mg2+]i) can potentially integrate the signals from hormones, cellular metabolism and organismal ion homeostasis and affect the activities of ion channel and other effectors. Interest in [Mg2+]i has been heightened by recent reports that small changes in [Mg2+]i in the physiological range can significantly modulate important cellular functions. In addition, a variety of new evidence shows that [Mg2+]i instantaneously changes following stimulation with various biologically active substances. These observations suggest that [Mg2+]i may act as a second messenger.

This study describes a new approach to targeting clustered genes. Our study began with the establishment of two lines of mice carrying different mutations in either Ren1 or Ren2. These two genes, both encoding renin, span over 40 kb in tandem on chromosome 1. Each gene was mutated by gene targeting to contain loxP sites. These two mutants and Cre transgenic mice were mated to produce offspring carrying the mutant Ren1 and Ren2 genes, as well as the Cre transgene concurrently. Initially, two mutant Ren genes were located on separate chromosomes. Southern analysis of mice from the second generation revealed that the mutant Ren1 and Ren2 were interchromosomally recombined at the loxP sites to produce a new dually mutated allele on the chromosome at the rate of 9.6% (7/73). Thus, interchromosomal recombination can be efficiently programmed by mating as designed using the Cre-loxP system., (Copyright 2000 Academic Press.)

Background: Nitric oxide (NO) is known to modulate myocardial contraction and coronary tone, and its inhalation reduces pulmonary vascular resistance in patients with pulmonary hypertension., Objectives: To evaluate the pathophysiological role of NO in patients with a ventricular septal defect (VSD)., Patients: Twenty-nine children with VSD, nine of whom had undergone VSD closure surgery, and 14 patients with Kawasaki disease. The mean age of the VSD patients was 3.1 years (range, 2 months to 9 years)., Methods: Using high performance liquid chromatography, nitrate (a more stable NO oxidation product) was measured in plasma specimens of the patients undergoing cardiac catheterisation., Results: Nitrate concentrations in the pulmonary artery bore a significant relation to mean pulmonary artery pressure, pulmonary to systemic systolic pressure ratio, and pulmonary to systemic flow ratio., Conclusions: The concentration of nitrate was in proportion to the increment in intravascular or cardiac pressure, indicating that endogenous NO is upregulated as a compensatory homeostatic attempt to reduce pulmonary pressure and blood flow.

Magnesium (Mg2+), the second most abundant intracellular cation, is a critical cofactor in numerous enzymatic reactions. After stimulation of platelets with insulin and insulin-like growth factor-1 (IGF-1), we examined changes in cytosolic free Mg2+ ([Mg2+]i) by using fluorescent probe magfura-2. Basal [Mg2+]i in platelets was 614 +/- 1 microM (mean +/- SEM, n = 60). Insulin and IGF-1 induced an immediate rise of [Mg2+]i in a dose-dependent manner. After stimulation of platelets with 100 microU/mL of insulin for 60 s, [Mg2+]i was significantly elevated to 1270 +/- 53 microM (n = 30, P < 0.05), i.e., 82 +/- 5% over resting [Mg2+]i. IGF-1 (5 micrograms/mL) also increased [Mg2+]i (1020 +/- 53 microM, 69 +/- 10% over resting [Mg2+]i, n = 30). In the medium containing choline instead of sodium or the medium without potassium, an elevation of [Mg2+]i with addition of insulin/IGF-1 was moderately suppressed. Amiloride, a Na+-H+ antiport inhibitor, did not block the insulin/IGF-1 effect. Insulin/ IGF-1 translocates Mg2+ from the extracellular space to intracellular space and these effects are affected by external sodium and potassium., (Copyright 1998 Academic Press.)

Unlabelled: Adrenal enlargement was followed by serial ultrasonography in an infant with congenital lipoid adrenal hyperplasia (lipoid CAH) from day 12 until 2 years and 4 months of age, when they were no longer detectable. Contrary to other types of CAH in which the configuration changes soon after replacement therapy, this infant with lipoid CAH showed persistent adrenal cortex enlargement due to massive accumulation of lipids and cholesterol resulting in a damaged glandular cyto-architecture., Conclusion: ultrasonographically persistent enlargement of the adrenals after replacement therapy is suggestive of the lipoid form of CAH.

A traumatic left bundle branch block (LBBB) is uncommon in a patient with intact atrioventricular conduction. Three of our patients developed LBBB during a left-sided catheterization. Two patients suffered from angina pectoris and the other had an abdominal aneurysm. Two of them had a history of hypertension. None of the patients had ever shown any conduction abnormalities before the catheterization. The electrocardiogram just before the examination was normal in all 3 patients. LBBB was observed when a catheter was introduced into the left ventricle, and lasted 2--4 min without significant change in heart rates. Examination revealed no significant stenosis proximal to the first septal perforator and normal left ventricular contraction in all patients. One patient developed permanent LBBB 14 months later. Catheter-induced LBBB may occur easily with certain anatomical characteristics of the left bundle branch or the distal His bundle, with or without some concealed damage to the conduction system. It is important to keep this complication in mind and to pay adequate attention to patients' electrocardiograms as well as their angiographical findings, especially in those with pre-existing right bundle branch block.

To elucidate the defense mechanism in neonates against bacterial infections, phagocytic activity and hydrogen peroxide (H2O2) production by polymorphonuclear leukocytes (PMNs) in the whole blood and the effects of plasma on these functions were investigated on 44 healthy mature neonates (term 37 to 41 weeks) and 15 premature neonates (term 30 to 36 weeks) using two color flow cytometric analysis. The results were compared to those of a healthy adult control group (n = 10). PMN phagocytic activity was low in both mature and premature neonates. H2O2 production of PMN with phorbol myristate acetate (PMA) stimulation and following phagocytosis was augmented in both mature and premature neonates. When plasma and PMNs of adults and neonates were separated and combined differently, phagocytic activity and H2O2 production of PMNs appeared to be principally regulated by the plasma employed. This finding indicates that plasma has major effects on both phagocytosis and H2O2 production by PMNs of newborn neonates.

Intracellular calcium ([Ca2+]i) and phorbol ester binding were studied in intact platelets of young patients with insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetes mellitus. Our objective was to evaluate disturbances in calcium regulation and signal transduction in platelets of diabetics. [Ca2+]i in platelets of the IDDM group (135 +/- 20 nmol/L) under basal conditions was significantly higher than that of the control group (81 +/- 8 nmol/L, P = .019), whereas at 60 seconds after stimulation with 0.1 National Institutes of Health (NIH) U/mL thrombin, [Ca2+]i in the NIDDM group (484 +/- 36 nmol/L) was significantly higher than that of the controls (347 +/- 22 nmol/L, P = .003) and IDDM group (360 +/- 45 nmol/L, P = .04), respectively. Phorbol 12,13-dibutyrate (PdBu) maximal binding capacity (Bmax) in the IDDM group was significantly lower than that in the control group either under basal conditions or after stimulation with thrombin (P = .0034 and P = .015, respectively). Bmax in the NIDDM group was significantly lower than that in the controls only after stimulation with thrombin (P = .047). The Kd for PdBu of the IDDM group was lower than that of the control group under basal conditions (P = .017). When analyzing the pooled data of all subjects, a significant correlation was observed between Bmax and Kd (under basal conditions, r = .544, P < .0001; after stimulation, r = .601, P < .0001). Our results support the idea that the increased affinity for PdBu may compensate for the decreased binding capacity. We interpret the data as indicating that the change in the binding of phorbol ester to protein kinase C (PKC) units may result in an altered PKC/calcium interaction in the pathogenesis of diabetes mellitus. Our study indicates that such metabolic derangements of [Ca2+]i have already been developing in young diabetic patients.

The study was designed to examine cytosolic free calcium ((Ca2+)i) and phorbol dibutyryl ester binding in intact platelets of young obese subjects as compared with the platelets of age-matched subjects with non-insulin-dependent diabetes mellitus (NIDDM) and those of healthy control subjects. The assay was studied in basal and thrombin-stimulated conditions. The binding parameter of phorbol ester is a criterion for active protein kinase C (PKC) units in the platelet plasma membrane. The resting (Ca2+)i correlated with body mass index (BMI)(r = 0.385, p = 0.0034) and plasma insulin level (r = 0.316, p = 0.0269), and the resting (Ca2+)i level was higher in the obesity group (160.6 +/- 15.8 nmol/L; n = 25) than controls (78.9 +/- 7.6 nmol/L; n = 24, p < 0.0001). Among the obesity and control groups, there was a correlation between BMI and fasting plasma insulin level (r = 0.399, p = 0.0237). Systolic blood pressure correlated with BMI(r = 0.504, p = 0.0005). The mean systolic blood pressure of the obesity group was higher than those of the other two groups. The mean Hill coefficient for thrombin-treated platelets of phorbol dibutyrate binding was higher in the obesity group when compared with healthy controls and the subjects with NIDDM (1.47 +/- 0.21 vs 1.06 +/- 0.16 and 0.99 +/- 0.09, respectively; p < 0.05). In conclusion, young subjects with simple obesity have already developed altered platelet Ca2+ regulation that is usually observed in adult patients with a number of metabolic diseases. These data are interpreted to indicate that a relationship exists between dysregulation of PKC and impaired glucose tolerance that precedes other complications of obesity.

We report the case of a 3-year-old boy with Ménétrier's disease who presented with prominent anasarca associated with hypoproteinemia, but no proteinuria. An early sonogram of the stomach demonstrated thickening of the gastric wall which was found to resolve gradually on serial sonograms. Consequently, we considered that the submucosal layer of the gastric wall was particularly thickened as a result of Ménétrier's disease. A gastric biopsy was performed 18 days after onset of the disease, and an electron-microscopic examination of the sample disclosed persistent widening of gastric tight junctions by more than 10 nm. The patient made a full recovery on supportive treatment in 3 weeks. Ultrasonography provided us with a potent tool not only in making the diagnosis, but also in following the course of the disease.

Azithromycin (AZM), 10% fine granules or 100 mg capsules, were given orally to 27 children with various pediatric infections. The results of the study are shown below. 1. Pharmacokinetic investigation. We studied plasma and urinary concentrations after 100 mg AZM capsules were given. One patient received 8.3 mg/kg of AZM once a day for 3 days, and AZM concentration in plasma was 0.033 microgram/ml 48 hours after the final dosing. Doses of 8.3 and 12.5 mg/kg body weight of AZM were respectively given to two patients once daily for 3 days. As a result, AZM concentrations in urine during a period between 96 and 120 hours post-dosing were 1.67 and 4.53 micrograms/ml, respectively, and urinary excretion rate in 120 hours after the first dosing was 10.54% in the patient that was given 12.5 mg/kg. 2. Clinical investigation. Clinical efficacies were examined in 24 patients. Excellent results were obtained in 7 patients, good results in 14 patients, hence the clinical efficacy rate was 87.5%. Bacteriologically, Haemophilus influenzae strains isolates from 2 patients were eradicated in 1 and decreased in the other. Safety was evaluated in 26 patients. An adverse reaction was observed in 1 patient (urticaria). Abnormal laboratory test results were observed in 2 patients, decreased WBC in 1 and elevation of eosinophils in the other. The above results suggest that AZM is a useful oral antibiotic for pediatric patients with infection with susceptible organisms.