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Biomedical subjects

H Blanchard

Publications and source records attributed to H Blanchard.

At least 37 records · Page 2Linked to original sources
PubMed1997

Structure of a calpain Ca(2+)-binding domain reveals a novel EF-hand and Ca(2+)-induced conformational changes.

The crystal structure of a Ca(2+)-binding domain (dVI) of rat m-calpain has been determined at 2.3 A resolution, both with and without bound Ca2+. The structures reveal a unique fold incorporating five EF-hand motifs per monomer, three of which bind calcium at physiological calcium concentrations, with one showing a novel EF-hand coordination pattern. This investigation gives us a first view of the calcium-induced conformational changes, and consequently an insight into the mechanism of calcium induced activation in calpain. The crystal structures reveal a dVI homodimer which provides a preliminary model for the subunit dimerization in calpain.

Amino Acid Sequence↗
PubMed1996

Ca(2+)-binding domain VI of rat calpain is a homodimer in solution: hydrodynamic, crystallization and preliminary X-ray diffraction studies.

The 21-kDa calcium-binding domain (VI) of the small subunit of rat calpain II has been expressed in Escherichia coli, purified, and crystallized. Two orthorhombic crystal forms have been obtained: space group P2(1)2(1)2(1) with a = 50.3, b = 56.5, c = 141.3 A; and space group C222(1) with a = 69.4, b = 73.9, c = 157.4 A. Diffraction data have been collected to 2.4 A. Sedimentation equilibrium, dynamic light scattering, and gel-permeation chromatography indicate that domain VI exists as a homodimer in solution. In accordance with the protein's behavior in solution, each crystal form contains two molecules per asymmetric unit. Screening for heavy-atom derivatives is in progress. To decrease the sensitivity to mercurials and to aid in the search for useful derivatives, Cys-to-Ser mutants have been prepared, expressed, and crystallized.

Animals↗
PubMed1996

Chromosomal anomalies in newborns with omphalocele.

Omphalocele is the most common congenital abdominal wall defect; its reported incidence is 1 in 4,000 to 5,000 live births. With large defects, the liver is a median organ and lies within the sac (extracorporeal liver [ECL]). With small defects, only bowel or stomach is found outside the abdominal cavity (intracorporeal liver [ICL]). The goal of this study was to determine whether a relationship exists between the sac contents or the timing of diagnosis and the incidence of chromosomal abnormalities or survival among fetuses and newborns with omphalocele. From 1985 to 1995, 83 cases of omphalocele were managed at the authors' institution. In 50 cases the diagnosis was made using prenatal ultrasonography. All patients underwent fetal cardiac echography and amniocentesis. Twenty-four pregnancies were terminated electively because of severe associated anomalies. Of the 59 live births, 41 patients (69%) survived. The incidences of cardiac, chromosomal, and other anomalies were 24% (14), 10% (6), and 21% (16), respectively. Omphalocele with ICL is associated with a better survival rate than omphalocele with ECL (82% v 48%; P < .01) despite the significantly higher rate of karyotype abnormalities (16% v 0%; P < .05). The prognosis was poorer for patients with prenatally diagnosed omphalocele than for those with a postnatal diagnosis (mortality rate, 42% v 21%) because the former group had a higher percentage (70% v 9%) of ECL. Although the incidence of cardiac anomalies was similar for the ECL and ICL groups (33% v 18%), the former had more complex malformations. Death usually occurred in newborns who had neonatal respiratory distress owing to prematurity, or in those with chromosomal or cardiac anomalies. Chromosomal anomalies occurred mainly in cases of small omphaloceles that contained gut only, and it was the major cause of death among this group. In ECL cases, survival was primarily affected by the associated complex cardiac anomalies.

Chromosome Aberrations↗
PubMed1995

Vascular complications after pediatric liver transplantation.

From February 1986 to July 1994, 81 hepatic transplantations were performed in 73 children, with an overall patient survival rate of 83%. Forty-two patients received whole-liver grafts (WLG) and 39 had reduced-size grafts (RSG). The mean patient weight was 19.7 kg, with 29 patients weighing less than 10 kg. Seventeen vascular complications (21%) occurred in 13 children: 8 (10%) had hepatic artery thrombosis (HAT), 5 (6%) had portal vein thrombosis (PVT), 1 had both HAT and PVT (1%), and 3 (4%) had aortic conduit perforation (ACP). There was no significant difference in the incidence of HAT between RSG (5%) and WLG (14%) or between children weighing less than 10 kg (10%) and those weighing more than 10 kg (10%). The site of arterial reconstruction, end-to-end to the recipient common hepatic artery or end-to-side to the infrarenal aorta, had no significant effect on the occurrence of HAT (7% v 8%), but HAT occurred in 2 of 6 cases (33%) in which an aortic conduit was used. PVT documented in 5 cases (6%) was associated with technical complications (2), preduodenal portal vein (2), and a circulating cardiolipid antibody (1), and required thrombectomy, with no graft loss. Combined HAT and PVT was found in one patient 2 years postretransplantation for HAT. Although graft function is normal, portal hypertension persists. The aortic conduit, used in six patients, led to arterial perforation (3), HAT (2), and death (2). Of the 8 cases of HAT, 1 was diagnosed during autopsy and 7 occurred within 30 days and required retransplantation (6) or thrombectomy with rearterialization (1).(ABSTRACT TRUNCATED AT 250 WORDS)

Anastomosis, Surgical↗
PubMed1994

A crystallographic re-investigation into the structure of Streptomyces griseus proteinase A reveals an acyl-enzyme intermediate.

A molecular dynamics (MD) simulation on the contents of two asymmetric units of the crystal structure of the bacterial serine proteinase, Streptomyces griseus proteinase A (SGPA), resulted in four dihydrogen phosphate anions migrating to form a cluster in a solvent region far removed from the protein surface. In an effort to provide experimental verification for this unexpected phenomenon, native SGPA crystals were soaked in 2.0 M KH2AsO4; intensity data were collected and difference electron density maps examined for evidence of H2AsO4- ion clusters. These maps did not corroborate the cluster observed in the MD simulation. They did, however, show positive electron density features located in the active site cavity that could be interpreted as a tetrapeptide, Gly-Ala-Ser-(beta-OH)Asp, covalently bonded to O gamma of Ser195 as an acyl-enzyme intermediate. There was also a peak of electron density corresponding to an ideal position for the hydrolytic water in the deacylation reaction. This density is centred 3.1 A from His57 N epsilon 2 and 2.7 A from the carbonyl-carbon atom of the planar acyl-ester bond of the complex. The carbonyl-oxygen atom of the ester is located in the oxyanion pocket and participates in hydrogen bonds with Gly193 NH (2.6 A) and Ser195 NH (3.0 A).

Acylation↗
PubMed1994

Structural and kinetic characterization of a beta-lactamase-inhibitor protein.

The past decade has seen an alarming worldwide increase in resistance to beta-lactam antibiotics among many pathogenic bacteria, which is due mainly to plasmid- or chromosomally encoded beta-lactamases that specifically cleave penicillin and cephalosporins, rendering them inactive. There is therefore a need to develop new strategies in the design of effective inhibitors of beta-lactamase. All the small-molecule inhibitors in clinical use are not very effective and are rapidly degraded. Furthermore, newly characterized mutants of the plasmid-mediated beta-lactamase TEM-1 are highly resistant to these small-molecule inhibitors, including clavulanic acid and tazobactam. It has been shown that Streptomyces clavuligerus produces an exocellular beta-lactamase inhibitory protein (BLIP; M(r) 17.5 K). Here we present data defining BLIP as the most effective known inhibitor of a variety of beta-lactamases, with Ki values in the subnanomolar to picomolar range. To identify those features in BLIP that make it such a potent inhibitor, we have determined its molecular structure at 2.1 A resolution. BLIP is a relatively flat molecule with a unique fold, comprising a tandem repeat of a 76-amino-acid domain. Each domain consists of a helix-loop-helix motif that packs against a four-stranded antiparallel beta-sheet (Fig. 1a). To our knowledge, BLIP is the first example of a protein inhibitor having two similarly folded domains that interact with and inhibit a single target enzyme.

Amino Acid Sequence↗
PubMed1994

Report of three gastric tumors in children.

The literature concerning gastric tumors in children is mainly limited to case studies. The authors reviewed 1,403 histological reports of pediatric gastric pathology (covering 10 years) at their institution. There were three gastric tumors of benign histology and no malignant tumors. The first patient was a 9 1/2-year-old boy who presented with several months of symptomatic, pH-probe-confirmed gastroesophageal reflux. He underwent placement of a Toupet antireflux valve. During laparotomy, a submucosal mass was discovered incidentally, on the greater curvature of the stomach. The mass was excised. Pathological examination showed heterotopic pancreas. The second patient, a 15-month-old girl, presented with a short period of vomiting. Results of an upper gastrointestinal series showed gastric outlet obstruction. She underwent laparotomy and was found to have an intussusception of a gastric polyp into the proximal jejunum, and an associated malrotation. Ladd's procedure, gastroduoduodenostomy with reduction of the intussuscepted polyp, and excision of the polyp were performed. Histological examination of the tumor showed hamartoma with hyperplastic elements. The tumor was benign but was regarded as difficult to classify. The third patient, a 6-year-old boy, presented with microcytic anemia. Endoscopy showed multiple friable bleeding gastric masses. He underwent laparotomy, with partial gastrectomy and pyloroplasty. Histological examination showed the tumor to be plasma cell granuloma. The tumor recurred, and the patient required subsequent operative procedures. The authors confirm that gastric tumors in children are rare. Although the tumor histology may be benign, excision of the tumor may require major operative resection.

Child↗
PubMed1994

Minimally conjoined omphalopagi: a consistent spectrum of anomalies.

Omphalapagus twins constitute less than one third of all siamese twins. Most omphalopagi are attached by a skin bridge that often contains hepatic tissue. Only four cases of omphalopagi attached by an intestinal bridge have been reported. The authors present two additional cases of conjoined twins minimally attached by a small bowel and bladder bridge. In both instances, the spectrum of anomalies included a ruptured omphalocele and imperforate anus with cloacal anomalies. The attachment consisted of an open urachal remnant joining the two bladders, and the short small bowel of twin A attached to the terminal ileum of twin B. Separation was uneventful. For one set of twins, the case part of the proximal colon of twin B was used to lengthen the bowel of twin A. Three of the twins survived and underwent additional procedures for repair of the cloacal anomalies. All four previously reported cases of minimally conjoined omphalopagi presented with a remarkably similar spectrum of anomalies. All had ruptured omphaloceles, imperforate anus with cloacal anomalies, and urachal anomalies. Intestinal connection was consistently at a point corresponding to the Meckel diverticulum site of twin B, with blood supply to the small bowel of twin A, probably via the vitelline artery. The consistent spectrum of anomalies encountered with minimally conjoined omphalopagi allows planning of separation. Caution is required to avoid overlooking the patent urachus, and intestinal lengthening procedures based on the vitelline artery become an important consideration.

Anus, Imperforate↗
PubMed1993

Biliary tract complications in pediatric orthotopic liver transplantation.

Biliary tract complications are reported in 15% to 30% of orthotopic liver transplantations (OLTs). Since 1986, 53 OLTs were done in 48 children with a mean age and weight of 5.3 years and 18.9 kg, respectively. Twenty-seven transplantations (51%) were reduced liver grafts (RLG) and 26 (49%) were whole liver grafts (WLG). Since 1988, 70% of transplantations have been RLG. Choledochocholedochostomy (mean weight, 25 kg) with a T-tube (CC) or choledochojejunostomy (CJ) (mean weight, 14.5 kg) were done in 24 (45%) and 29 (55%) cases, respectively. The overall mortality was 19% but none of the deaths were related to biliary problems. There were 13 biliary tract complications (24.5%) in 11 patients including 7 leaks, 5 obstructions, and 1 intrahepatic biloma. Leaks leading to bile peritonitis were managed with simple suture and drainage and were related to the T-tube (4), to the Roux-en-Y loop (2), and to the transection margin of a RLG (1). Obstruction was documented in 5 cases with none associated with hepatic artery thrombosis (HAT). Stenosis after CC reconstruction (2) required conversion to CJ. Two patients had revision of CJ because of kinking of the common bile duct after a left lateral segment graft and an anastomotic stricture 46 months after OLT. The last patient developed a vanishing bile duct syndrome 4 months posttransplant and is awaiting retransplantation. One patient had multiple episodes of cholangitis after HAT and was retransplanted. Neither the type of grafts (RLG 25.9% v WLG 23.1%) nor the type of biliary reconstruction (CC 25% v CJ 24%) influenced the rate of biliary complications.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Metabolism, Inborn Errors↗
PubMed1993

Surgical and metabolic aspects of liver transplantation for tyrosinemia.

Tyrosinemia is the diagnosis of a very small percentage of patients undergoing liver transplantation worldwide. Tyrosinemia is endemic within our referral area however, and fully one-third of the liver transplantations at our institution are done for this disease. Since 1986, 15 patients with tyrosinemia (TYR) and 31 patients with various other indications (non-TYR) have undergone a total of 51 liver transplantations. The 36-month actuarial survival for TYR patients is 87%, compared with 74% for non-TYR patients. Liver transplantation for hereditary tyrosinemia and other metabolic disorders without portal hypertension or previous portohepatic operations is notably easier to perform. Intraoperative blood loss was less, length of hospital stay was shorter, and incidence of infections was lower in TYR than in non-TYR patients. Less than 10% of TYR patients had foci of hepatocellular carcinoma at the time of transplantation. For this reason, and while most patients with tyrosinemia will eventually require liver transplantation, our results do not support systematic early transplantation before the age of two years.

Adolescent↗
PubMed1993

[Surgical and metabolic aspects of liver transplantation for tyrosinemia].

Tyrosinemia represents a very small percentage of patients undergoing liver transplantation world-wide. This disease is endemic within our referral area however, one-third of the liver transplantations at our institution are done for this disease. Since 1986, 16 patients with tyrosinemia and 34 patients with various other indications (non-tyrosinemic) have undergone a total of 55 liver transplantation. The survival rate for tyrosinemic patients is 87%, compared to 75% for non-tyrosinemic patients. Liver transplantation for hereditary tyrosinemia and other metabolic disorders without portal hypertension or previous portohepatic operations is notably easier to perform. Intraoperative blood loss was less, length of hospital stay was shorter and incidence of infections was lower in tyrosinemic than in non-tyrosinemic patients. Less than 10% of tyrosinemic patients had foci of hepatocellular carcinoma at the time of transplantation. For this reason, and while most patients with tyrosinemia will eventually require liver transplantation, our results do not support systematic early transplantation.

Adolescent↗
PubMed1993

[Biliary complications in pediatric liver transplantation].

Biliary tract complications are reported in 15% to 20% of orthotopic liver transplantations (OLT). Since 1986, 55 OLT were done in 50 children with a mean age and weight of 5.6 years and 18.8 kg respectively. There were 28 (51%) reduced liver grafts (RLG) and 27 (49%) whole liver grafts (WLG). Since starting using RLG in 1988, 70% of transplantations have been RLG. Choledochocholedochostomy with a T-tube (CC) or choledochojejunostomy (CJ) were done in 25 (45%) and 30 (55%) cases, respectively. The overall mortality was 19% with one death related to biliary problems. There were 14 biliary tract complications (25%) in 12 patients including 7 leaks, 6 obstructions and one intrahepatic biloma. Leaks leading to bile peritonitis were managed with simple suture and drainage and were related to the T-tube (4, to the Roux-en-Y loop (2) and the transection margin of a RLG (1). Obstruction was documented in 6 cases, none of which were associated with hepatic artery thrombosis (HAT). Stenosis after CC reconstruction (3) required conversion to CJ. Two patients had revision of CJ because of kinking of the common bile duct and an anastomotic stricture 46 months after OLT. One patient developed a vanishing bile duct syndrome 4 months post-transplant and died while waiting for retransplantation. One patient had multiple episodes of cholangitis after HAT and was retransplanted. The rate of biliary complications was not influenced by neither the type of graft (RLG : 25% vs WLG : 25,9%) nor the type of biliary reconstruction(CC : 28% vs CJ : 23%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Diaphragm of the gallbladder: a case report.

Gallbladder anomalies are rare and normally affect its shape, size, and position. We report on a 3-year-old boy with a gallbladder divided transversally by a windsock-type diaphragm, isolating the fundus from the rest of the biliary tree. Bilobed and multiseptated gallbladder have been described before, but this is the first isolated case of a congenital hourglass gallbladder.

Child, Preschool↗
PubMed1992

Neonatal gastrointestinal perforations.

Neonatal gastrointestinal perforation has been associated with mortality rates of 40% to 70%. Over the past 20 years, 81 infants (46 boys and 35 girls) were treated for a gastrointestinal perforation at this institution. Perforation occurred from birth to 50 days (average, 8.2 days). Etiologies included necrotizing enterocolitis (NEC) (68%), meconium ileus (10%), and idiopathic gastric perforation (7%). Seventy-six infants underwent surgical exploration and five infants, considered too small or too sick to withstand a laparotomy, were treated with peritoneal lavage only. There were 29 deaths, an overall mortality of 36%. Ninety percent of the death occurred in patients with NEC, while all patients with gastric perforations survived. There has not been a significant improvement in survival in recent years, partly because of an increase in the proportion of NEC-related perforations. However, there is a narrowing of the mortality gap between low birth weight and normal weight infants. As the risk inherent to laparotomy in neonates is decreasing, other factors, such as the underlying etiology or the site of perforation, play a more important prognostic role.

Enterocolitis, Pseudomembranous↗
PubMed1992

Complications of lymphangiomas in children.

One hundred ninety-three cases of lymphangioma presenting in children were reviewed over a 10-year period. The diagnosis was established before 5 years of age in 87.0%. The distribution of lymphangiomas was: cervical (31.4%), craniofacial (18.9%), extremity (18.9%), trunk (9.2%), intraabdominal (9.2%), cervicoaxillothoracic (4.9%), multiple (3.8%), cervicomediastinal (2.2%), and intrathoracic (1.6%). Of 164 patients undergoing primary therapy, total excision was performed in 77.4% and partial excision in 20.7% with recurrence rates of 11.8% and 52.9%, respectively. Thirty-eight percent of all operations for lymphangiomas were performed for resection of recurrent or residual disease. The incidence of postoperative complications was 31.3%. Forty-four additional procedures were required to manage these complications. Sclerotherapy with 50% dextrose was used as an adjunct in 9.5%. Recurrences were seen after total resection in 17.6% of operations in which 50% dextrose was used and 11.8% in which it was not used. Seroma formation was noted in 3.5% of total resections and 40.0% of resections for recurrent disease in which adjunctive sclerotherapy with 50% dextrose was used. Seromas occurred in 9.8% of wounds in which local drains were used and 3.6% of wounds in which drains were not used. Infectious complications occurred after 6.6% of operations using perioperative antibiotics and 3.5% not using antibiotics. The management of lymphangiomas in children remains a difficult problem. Despite being benign lesions, lymphangiomas are attended by a high rate of morbidity from complications of the disease and its management. Complete excision still offers the best chance for complete cure. Sclerotherapy with 50% dextrose is not beneficial in the management of recurrent disease or postoperative seromas. Local drains and perioperative antibiotics do not appear to diminish the incidence of seromas and infectious complications, respectively.

Child, Preschool↗