[Renal involvement in the Alagille syndrome].
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Abnormalities, Multiple↗
Biomedical subjects
O Bernard
Publications and source records attributed to O Bernard.
[Status epilepticus in an asthmatic child].
BACKGROUND: Chronic administration of theophylline can be used for treating asthma; it may represent a severe risk when some other drugs are prescribed by unaware physicians. CASE REPORT: A 4 yr-8-mo-old boy was admitted suffering from status epilepticus which occurred 3 hours after vomiting. This patient had asthma and was given sustained-release formulation of theophylline and, independently by another physician, two anti-H1 drugs: ketotifen and mequitazine. Serum theophylline concentration measured 9 hours after the onset of vomiting was 28 micrograms/ml; the calculated concentrations were 45.3 +/- 4, 40.2 +/- 4 and 33.4 +/- 4 micrograms/ml after the last administration of theophylline, the onset of vomiting and the onset of seizures, respectively. The patient was given IV fluids plus clonazepam and recovered completely. CONCLUSION: Severe poisoning can be seen with moderately increased blood levels of theophylline when this drug is chronically administered. Association of other drugs such as anti-H1 could represent an additional risk.
Asthma↗
Kiz-1, a protein with LIM zinc finger and kinase domains, is expressed mainly in neurons.
The olfactory epithelium is the only neuronal tissue capable of generating new neurons during adult life and hence must express genes responsible for this phenomenon. Therefore, we have used mRNA from immortalized olfactory epithelial cells to search for novel protein tyrosine kinases by polymerase chain reaction, using as primers conserved sequences from the catalytic domain of known kinase genes. A full-length complementary DNA clone corresponding to one such polymerase chain reaction product was isolated and sequenced. This complementary DNA, designated Kiz-1, encodes a protein containing two prominent domains; the NH2-terminal region contains a cysteine/histidine-rich moiety previously identified as a zinc-finger domain in proteins of the LIM family, while the COOH-terminus contains a kinase domain. Kiz-1 is expressed mainly in the brain of adult mice but also in a range of cultured cell lines, regardless of their tissue of origin. Immunohistochemical studies on adult mouse brain demonstrated that Kiz-1 is expressed exclusively in neurons, not in astrocytes or oligodendrocytes. In the developing embryo, however, Kiz-1 is expressed in all tissues. In COS cells transfected with Kiz-1 complementary DNA and in the immortalized olfactory epithelial cells, Kiz-1 was found mainly in the cytoplasm, but in neurons of the adult brain, it resided also in the nucleus. Two Kiz-1 mRNA species are expressed in cell lines as well as in the murine and human brain. One transcript lacks a region of 60 nucleotides, which lies within the catalytic domain of the kinase and is encoded by a separate exon. Our results suggest that Kiz-1 may play distinct roles in dividing cells and in differentiated neurons.
Amino Acid Sequence↗
Fibrolamellar hepatocellular carcinoma: report of a case mimicking a liver abscess.
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Carcinoma, Hepatocellular↗
Alterations of the putative tumor suppressor gene p16/MTS1 in human hematological malignancies.
The chromosome band 9p21-22 is frequently rearranged or deleted in a variety of tumors including hematological malignancies. This supports the notion of a tumor suppressor gene in this chromosome region. Indeed, the p16/MTS1 gene encoding a cyclin-dependent kinase (CDK) inhibitor has been shown to be frequently deleted and/or inactivated by nonsense mutations in a number of tumors. We have examined 98 DNA samples from blood, bone marrow cells and lymph node biopsies of patients with leukemia (ALL and AML) or lymphoma (follicular lymphoma and T-cell lymphoma), using Southern blot hybridization and a p16/MTS1-specific probe. Molecular abnormalities, mainly homozygous deletions, were found principally in ALL (8 out of 22 patients), much less frequently in AML (2/32) and lymphoma (2/32). While these data argue in favor of a large involvement of p16/MTS1 in ALL, AML and lymphomas appear to be less frequently implicated.
Adult↗
[Ascites after liver transplantation in children].
The objective of this study, based on a series of 148 transplants performed in 131 children, was to evaluate the frequency, complications and predisposing factors of ascites occurring after liver transplantation (LT). The diagnosis of post-LT ascites was defined as a drainage rate greater than 25 ml/kg/day (or- > 500 ml/day) persisting for at least 72 hours after removal of the drains. Among the 123 transplants analysed, 31 (25.2%) were complicated by ascites (group I). Group II consisted of 92 LT without ascites. This ascites was predominantly lymphocytic (669 +/- 1,104/mm3), rich in proteins (32 +/- 13 g/l), with a low triglyceride concentration. The mean duration of ascites was 25 +/- 19 days. Complications of ascites included: infection of ascitic liquid (35%), respiratory complications (65%), parietal complications (50%), consumption coagulopathy (35%), functional renal failure (Creat > 130 mumol/l, 35%). There were 9 deaths (29%) in group I versus 8 in group II (p < 0.02). The predictive factors, pre-LT, of postoperative ascites included: serum bilirubin > 300 mumol/l (p < 0.02); PT < 30% (p < 0.05); and serum albumin < 30 g/l (p < 0.05). Intraoperative factors favouring the development of ascites were end-to-side cavo-caval implantation of the graft when it was reduced (p < 0.02) and a volume of transfused blood after unclamping greater than 60 ml/kg (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Early radionuclide detection of intrapulmonary shunts in children with liver disease.
UNLABELLED: In order to detect and quantify intrapulmonary shunts in children with liver disease, a radionuclide method was developed and evaluated in such a population. METHODS: We studied 135 children in whom the severity of liver disease, in most cases, justified consideration of liver transplantation. Patients were separated into two groups according to their resting PaO2 values under room air: 109 children were normoxic and 26 were hypoxic. A radionuclide scan was performed immediately after intravenous injection of human albumin macroaggregates. Activity of the lungs (L) and brain (B) was counted. A shunt index (SI) was calculated as SI = 100.B/L. We compared this index with blood gases and clinical follow-up. RESULTS: In the normoxic group, SI was 0.43 +/- 0.30 (mean +/- s.d.); none of the 102 children with SI < 1 developed hypoxemia during their follow-up. Two of the six children with SI > 1 developed subsequent hypoxemia. In the hypoxic group, the nine children with SI < 1 did not aggravate their hypoxemia during follow-up. The 17 hypoxic children with SI > 1 later developed severe hypoxemia. CONCLUSIONS: Scintigraphy with intravenous human albumin macroaggregates is more accurate than measuring arterial blood gases to detect IPS in children with cirrhosis.
Arteriovenous Fistula↗
GATA-and SP1-binding sites are required for the full activity of the tissue-specific promoter of the tal-1 gene.
The tal-1 gene, which is frequently activated in human T cell acute leukemias (T-ALLs), codes for a protein of the basic helix-loop-helix family (b-HLH) and potentially a transcription factor. In human and murine hematopoiesis tal-1 is expressed during the differentiation of the erythroid, megakaryocytic and mastocytic cell lineages. The expression of tal-1 appears to be comodulated with that of the transcription factor GATA-1 gene, suggesting that the GATA-1 protein may regulate the tal-1 gene activity in these hematopoietic lineages. To get further insights into the molecular mechanisms that control tal-1 expression, we have isolated 5' sequences of the murine gene and compared them to their human counterparts. The 5' flanking sequences from the two genes show several regions of high homology. The alignment of both sequences enabled us to predict that similarly, to the human, the mouse gene contains two alternative first exons (Ia and Ib). Remarkably, in both species, the proximal region of the tissue-specific exon Ia (i.e. gene segment -122 to +1) contains two GATA-motifs (at -65 and -33) and one SP-1 consensus binding site (-59). Mobility shift assays demonstrate that GATA proteins are able to interact with both GATA-motifs in a sequence specific fashion, but with different efficiencies. Moreover transfection studies show that the GATA-1 protein directly mediates tal-1 transcription by interacting with the -122/+1 fragment, defined as a minimal promoter in erythroid cells. Mutagenesis of the promoter establishes that the -33 GATA-binding site present in this fragment is critical for tal-1 expression in erythroid cells, but by itself does not lead to full promoter activity. Indeed, further mutations show that the second -65 GATA-binding site and the binding motif for SP1 (-59) significantly contribute to the overall activity of the proximal tal-1 promoter. Altogether, our data provide evidence that GATA-1 cooperates with the transcription factor SP1 to mediate the erythroid-specific expression of the tal-1 gene.
3T3 Cells↗
Hunting 11q23 deletions with fluorescence in situ hybridization (FISH).
Seven patients with acute leukemia and translocation involving band 11q23 have been studied by fluorescence in situ hybridization (FISH) using YAC probes spanning the HRX gene. While hybridization signal was split by translocation between the rearranged 11 and the partner chromosomes in five patients, only one signal on the derivative 11 was observed in two patients, one with t(9;11)(p21-22;q23) and the other with t(6;11)(q27;q23). Having shown that HRX was rearranged in these two cases, the distal part of 11q23 was investigated using other YACs containing markers for this region. This showed that a 600-700 kb deletion, distal to the HRX breakpoint cluster region, had occurred in the two cases. This study supports the notion that the 5' end of HRX is the important part in the chimeric genes resulting from 11q23 translocations and suggests that deletions of the 3' part are not uncommon.
Adult↗
Extrafascial hyper-reduction of the hepatic graft.
The technique and limits of graft reduction in orthotopic liver transplantation (OLT) are not well-defined, especially for small recipients. To reduce the hepatic graft to the left lateral segment (segments II and III), the authors have used an extrafascial hepatectomy without any dissection of the hepatic hilum. Among 165 pediatric OLT, 22 procedures using such hyper-reduced hepatic grafts were performed upon 21 children of median age 2.6 years between 1988 and 1992. These 22 hyper-reduced hepatic grafts were transplanted orthotopically with conservation of the inferior vena cava of the recipient. The three-year patient survival rate was 66 percent (80 and 50 percent for those patients undergoing elective and emergent procedures, respectively). The main postoperative complications were: primary graft nonfunction (n = 1), arterial complications (n = 2), portal vein thrombosis (n = 1), intra-abdominal bleeding (n = 2) and biliary complications (n = 2). This technique is useful in instances of a large size discrepancy between the donor and recipient. However, it does not increase per se the absolute number of hepatic grafts available for transplantation.
Adolescent↗
Correction of phenylketonuria after liver transplantation in a child with cirrhosis.
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Child↗
Antiapoptotic effect of heterozygously expressed mutant RI (Ala336-->Asp) subunit of cAMP kinase I in a rat leukemia cell line.
cAMP induced rapid apoptosis (> 90% cell death in 6 h) of non-growth-arrested rat leukemia IPC-81 cells. A cell clone selected for cAMP resistance had a normally functioning apoptotic machinery whose triggering required about 30-fold higher cellular cAMP than in the parent cells. The cAMP subresponsiveness was due to a heterozygous point mutation (Ala336-->Asp) in the RI subunit of cAMP-dependent protein kinase I. In fact, apoptosis correlated with intracellular cAMP binding to the subresponsive RI. The mutated alanine is invariantly present in cyclic nucleotide kinases, but of unknown function. The mutation decreased the cAMP affinity to site B by increasing the cAMP dissociation rate 500x. The ability of site B to discriminate adenine-modified cAMP analogues was affected, suggesting that Ala336 faced the adenine moiety of cAMP. That the heterozygously expressed RID336 was a dominant suppressor of apoptosis was explained by a higher expression of R than C subunits in the mutant cells by preferential expression of the mutant form of RI, and by the ability of mutant RI to exert dominant negative control of activation of wild type cAMP kinase at moderate cAMP levels. Apoptosis was induced at a similar cAMP level in cells treated with cholera toxin or other cAMP elevating agents, indicating that cAMP kinase was essential for toxin action.
Alanine↗
Expression of tal-1 and GATA-binding proteins during human hematopoiesis.
Tal-1 rearrangements are associated with nearly 30% of human T acute lymphoblastic leukemia. Tal-1 gene encodes a putative transcription factor with a basic helix-loop-helix domain and is known to be predominantly expressed in hematopoietic cells. We investigated the pattern of tal-1 expression in purified human hematopoietic cells by in situ hybridization and reverse transcriptase polymerase chain reaction analysis. Both methods demonstrated that the tal-1 gene is expressed in megakaryocytes and erythroblasts as well as in basophilic granulocytes. In addition, our results indicate that the tal-1 1A promoter, which contains two consensus GATA-binding sites, is active mainly in these lineages. Because the GATA-1 gene is known to transactivate several genes specific for the erythroid, megakaryocytic, and mastocytic/basophilic lineages, we studied GATA-1 expression in these purified hematopoietic cells. We found that GATA-1 and tal-1 genes are coexpressed in these three lineages. Remarkably, the expression of both genes is downmodulated during erythroid and megakaryocytic terminal maturation. In immature hematopoietic cells, tal-1 and GATA-1 genes are coexpressed in committed progenitors cells (CD34+/CD38(2+)), whereas they are not detectable in the most primitive cells (CD34(2+)/CD38-). In contrast, GATA-2 is strongly expressed in both most primitive and committed progenitors cells, whereas GATA-3 is mostly detected in most primitive ones. Altogether our results strongly suggest that GATA-1 modulates the transcription of tal-1 during the differentiation of the erythroid, megakaryocytic, and basosophilic lineages.
Adult↗
Controlled liver splitting for transplantation in two recipients: technique, results and perspectives.
A technique of controlled liver splitting for transplantation in two recipients is proposed, based on a full anatomical assessment of the graft including arteriography and cholangiography on the back-table. Using eight livers, 16 patients received a graft: right liver (eight patients), left lobe (four) or left liver (four). Twelve patients required urgent or very urgent transplantation. Anatomical assessment of the graft demonstrated a portal bifurcation in all cases, a common trunk of the left and middle hepatic veins in five, a right biliary duplication in three and duplication of the left branch of the middle hepatic artery in one. After revascularization of the graft, bleeding was greater in patients with a right graft, particularly if the middle hepatic vein had been ligated. The main postoperative complications were hepatic artery thrombosis (four cases), biliary complications (four), portal vein thrombosis (two), haematoma (two) and abscess (two). No primary non-function of the graft was observed. The postoperative survival rate was 75 per cent. The four patients in whom transplantation was not considered urgent are still alive. The immediate survival rate of the grafts was 69 per cent. These results compare favourably with those in the literature. In spite of the technical, logistical and ethical problems raised by this technique, the results suggest that controlled liver splitting for transplantation in two recipients may in the future significantly improve the feasibility of liver transplantation.
Adolescent↗
Cholelithiasis in infancy: a study of 40 cases.
During a 17-year period, 40 infants less than 1 year of age were investigated for cholelithiasis; 32 infants were seen within the past 10 years. Seventeen of them had no recognizable predisposing factors. In 6 infants, gallbladder lithiasis was a fortuitous finding on a plain radiograph or sonogram with no signs of common bile duct obstruction; under conservative management, no complications of lithiasis were observed on follow-up of 3 infants and spontaneous resolution occurred in 2 others. In the remaining 34 infants with lithiasis of the common duct or cystic duct or both, the initial symptoms were cholestatic jaundice in 21, acholic stools in 8, sepsis in 4, and abdominal pain in 1. Ultrasonography, performed in 33 of them, showed dilation of the biliary tract in 28, and stones in the gallbladder in 13 and in the bile ducts in 10. Percutaneous transhepatic cholangiography or operative cholangiography in 26 infants showed stones in the bile ducts in 23. In 3 infants, no lithiasis was visible, suggesting the spontaneous elimination of stones. Treatment was initially surgical in 9 infants, but starting in 1981 interventional radiologic procedures were attempted in 15 infants and were successful in 12. Spontaneous resolution of cholelithiasis occurred in 10 other infants with cholestasis. Recurrence of biliary stones was observed in 3 infants only after a follow-up of 7 months to 10 years. These results suggest that common bile duct lithiasis should be considered among the causes of cholestatic jaundice in infancy, and that some of the gallbladder calculi found in older children may have resulted from a lithogenic process that occurred during fetal life or shortly after birth. Percutaneous cholangiography with biliary drainage appears to be an effective means of treatment of infants with common bile duct obstruction; surgery can then be restricted to a limited number of cases, especially those with associated strictures of the bile ducts.
Bile↗
Autoimmune hepatitis associated with anti-actin antibodies in children and adolescents.
The clinical, biochemical, morphological, and evolutive features of autoimmune hepatitis associated with serum smooth muscle antibodies of anti-actin specificity were retrospectively analyzed in 31 children and adolescents. Cirrhosis was present at diagnosis in all but six patients, including nine of the 12 diagnosed within 6 months from the onset. In 15 children, one or more associated diseases of an immune-mediated mechanism were present, including chronic arthritis, sclerosing cholangitis, inflammatory bowel disease, and cutaneous vasculitis. All patients were treated with prednisone and azathioprine with normalization or improvement of liver function tests: 28 children are currently alive after a mean follow-up of 4 years, 10 months. Treatment was interrupted in four patients only. Two patients died of liver failure in spite of immunosuppressive therapy before the era of liver transplantation. In spite of prolonged therapy, five other patients ultimately required liver transplantation during adolescence or early adulthood. These results (a) further define a group of autoimmune hepatitis in children characterized by the presence of serum anti-actin antibodies; (b) indicate that immunosuppressive therapy improves liver function, although in most cases it must be continued for a long period to maintain remission; and (c) suggest that progressive liver failure may occur in early adulthood and may require liver transplantation.
Actins↗
Hepatitis C virus infection in pediatric liver transplantation.
To determine the prevalence of antibodies to hepatitis C virus (HCV) and the short-term evolution of HCV infection in children undergoing orthotopic liver transplantation, we retrospectively studied the sera and medical records of 149 children surviving from 9 months to 5 years after OLT. Fourteen children (9.4%) were found to be positive for anti-HCV with second-generation ELISA and RIBA tests. They were individualized in 2 distinctive groups. In 5 children, anti-HCV was present before OLT, and in 1 patient only HCV RNA was detected at that time. All 6 patients were positive for anti-HCV after OLT. In the other 8 children, anti-HCV and HCV RNA were only detected after OLT and likely reflect infection during or shortly after OLT. The antibody reactivities against the 3 antigens included in the second-generation RIBA test varied in a given patient throughout follow-up and between these 2 groups of children. In all patients, serum transaminase (ALT) activities returned to normal levels when prednisone therapy was lowered and given every other day. These results indicate that the search for HCV infection in these children is necessary in the differential diagnosis of other liver complications in order to avoid excessive immunosuppressive treatment.
Adolescent↗
A novel translocation, t(9;11)(q33;q23) involving the HRX gene in an acute monocytic leukemia.
A t(9;11)(q33;q23) has been detected by chromosome painting with chromosome 11- and chromosome 9-specific probes in blast cells of a child with acute monocytic leukemia. Using a YAC clone spanning the usual breakpoint region of translocations of acute leukemias, it was shown that the breakpoint was effectively within the same region of the band 11q23. This was confirmed by Southern blot studies that showed the localization of the translocation breakpoint between the 6th and 8th exons of the HRX gene. The implication of the HRX gene in t(9;11)(q33;q23) is a novel example of the diversity of translocations involving this gene in hemopoietic disorders. Sequencing DNA in the vicinity of the breakpoints should help to understand the reason of the localization of the recombination hot spot at band 11q23.
Adult↗