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Biomedical subjects

A Vos

Publications and source records attributed to A Vos.

At least 19 recordsLinked to original sources
PubMed1999

Dissecting the role of the N-terminal domain of human immunodeficiency virus integrase by trans-complementation analysis.

The human immunodeficiency virus (HIV) integrase protein (IN) catalyzes two reactions required to integrate HIV DNA into the human genome: 3' processing of the viral DNA ends and integration. IN has three domains, the N-terminal zinc-binding domain, the catalytic core, and the C-terminal SH3 domain. Previously, it was shown that IN proteins mutated in different domains could complement each other. We now report that this does not require any overlap between the two complementing proteins; an N-terminal domain, provided in trans, can restore IN activity of a mutant lacking this domain. Only the zinc-coordinating form of the N-terminal domain can efficiently restore IN activity of an N-terminal deletion mutant. This suggests that interaction between different domains of IN is needed for functional multimerization. We find that the N-terminal domain of feline immunodeficiency virus IN can support IN activity of an N-terminal deletion mutant of HIV type 2 IN. These cross-complementation experiments indicate that the N-terminal domain contributes to the recognition of specific viral DNA ends.

Animals↗
PubMed1998

Clenbuterol as a marker in baits for oral vaccination of dogs against rabies.

Clenbuterol was investigated as a potential marker of baits for the oral vaccination of dogs (Canis familiaris) against rabies in Turkey. Orally administered clenbuterol is incorporated into the hair fibre during hair growth, and the uptake of clenbuterol into the hair of 18 dogs was therefore investigated in a controlled laboratory experiment. Clenbuterol could be detected in the hair of the dogs 28 and 56 days after they had eaten a bait containing 0-5 mg clenbuterol. In a field study, 150 baits containing clenbuterol were of distributed at selected sites along roads in the suburban areas of Ferhatpasa, Istanbul; the baits incorporated a vaccine container with the live modified rabies virus vaccine SAD B19. By the following morning, 93 per cent of the baits had gone. Hair samples from nine of 31 recaptured dogs contained more than 1 ng clenbuterol/g, indicating that they had consumed a bait. However, only four of the 31 dogs had an increased antibody titre. The results of this field study indicate that the placing of baits at selected sites is not a very efficient method of vaccinating ownerless dogs.

Administration, Oral↗
PubMed1998

[Feeding tubes for tube feeding].

Several techniques are available for the provision of enteral nutritional support. Nasal tubes, gastrostomy tubes and jejunostomy tubes can be distinguised. Nasal tubes are used for short-term support, gastrostomy tubes (preferably via a percutaneous endoscopic gastrostomy) for long-term support (over 4 to 6 weeks), while (needle catheter) jejunostomy tubes are most often used to provide early enteral nutrition immediately after operations on the proximal gastrointestinal tract. The most frequent complications are: with the nasal tube dislodging, clogging and aspiration, with the gastrostomy tube peristomal infection and with the jejunostomy tube, obstruction. It should further be noted that the quantity of enteral nutrition prescribed and that actually administered may differ substantially so that patients with a feeding device may even become malnourished. With proper patient selection and secure control of the energy balance, feeding tubes are simple (temporary) devices that improve the patient's health and quality of life.

Enteral Nutrition↗
PubMed1998

MR imaging of anorectal malformations and associated anomalies.

Congenital anorectal malformations are found in many forms, and are frequently associated with other anomalies, especially of the spinal cord, spine, and urogenital system. Decisions concerning initial management of children with anorectal malformations can be made only after accurate determination of (a) the level and type of malformation, (b) the type of fistula, (c) the developmental state of the sphincter muscle complex, and (d) the presence of associated anomalies. Magnetic resonance imaging has proven to be the only modality to answer all these crucial questions, and has contributed to a better insight in the morphology and pathogenesis of such complex congenital malformations.

Abnormalities, Multiple↗
PubMed1998

Surgical treatment of diaphragmatic eventration caused by phrenic nerve injury in the newborn.

BACKGROUND: Phrenic nerve palsy in infants and young children usually results from birth injury or iatrogenic damage. The newborn almost invariably presents with severe respiratory distress, diaphragmatic elevation, and paradoxical movement at the affected side. METHODS/RESULTS: In this retrospective analysis a group of 23 patients below the age of 1 year with an obstetric or postoperative phrenic nerve injury was studied and compared with cases in the literature. All patients were admitted between 1986 and 1997 to the Pediatric Surgical Center, Amsterdam. Thirteen of 18 patients with an obstetric phrenic nerve injury underwent plication of the diaphragm after an average observation period of 100 days. In the remaining five children with an obstetric phrenic nerve injury, spontaneous recovery appeared within 1 month. Only one of five patients with a phrenic nerve palsy after a cardiac surgical procedure underwent plication of the diaphragm. Fifteen of the 34 patients described in the literature underwent plication of the diaphragm after an average of 54 days. CONCLUSIONS: If after 1 month no spontaneous recovery of the diaphragmatic paralysis caused by a phrenic nerve injury occurs, plication of the diaphragm is indicated. This operation proved to be successful for relief of symptomatic phrenic nerve injury in all cases. If the condition of the patient clinically deteriorates during this first month of life, the patient should be operated on immediately.

Birth Injuries↗
PubMed1998

Predictors of recurrence of fulminant bacterial peritonitis after discontinuation of antibiotics in open management of the abdomen.

OBJECTIVE: To assess a scoring system for predicting recurrence of fulminant bacterial peritonitis after discontinuation of antimicrobial treatment in patients being treated by open management of the abdomen for persistent bacterial peritonitis after perforation of the digestive tract, anastomotic disruption, or necrotising pancreatitis. DESIGN: Retrospective study. SETTING: University Hospital, The Netherlands. SUBJECTS: 58 consecutive patients. MAIN OUTCOME MEASUREMENTS: Recurrence of fulminant bacterial peritonitis and survival. RESULTS: 13 of the 58 patients (22%) died during the initial course of antimicrobial drugs. 14 of the remaining 45 patients had a recurrence of fulminant bacterial peritonitis after discontinuation of antimicrobial drugs, 4 of whom died. Predictive criteria included raised white cell count (WCC) (p = 0.02), duration of initial antibiotic treatment (p = 0.05), and deterioration in Simplified Acute Physiology Score (p = 0.05). Using the WCC and the duration of initial antimicrobial treatment together with other variables that showed a predictive trend (body temperature, percentage band cells, underlying disease, and use of inotropic agents), in a new scoring system (0-12), fulminant bacterial peritonitis did not recur when the score was 0-3, but in 9 of 11 patients with a score of 6 or more it did (p < 0.001). CONCLUSION: Patients at increased risk of recurrence of fulminant bacterial peritonitis during open management of the abdomen can be identified at the time of discontinuation of antimicrobial treatment by a new scoring system; antimicrobial treatment should not be discontinued in patients with a score of 6 or more.

Adult↗
PubMed1998

Gastrointestinal motility and gastric tube feeding in mechanically ventilated patients.

OBJECTIVE: To determine the fasted and fed gastrointestinal motility characteristics that are possibly responsible for gastric retention in mechanically ventilated patients. DESIGN: Prospective, case series. SETTING: Surgical intensive care unit of a university hospital. PATIENTS: Seven patients who required mechanical ventilation for thoracic or combined thoracic-neurologic injuries and nine healthy volunteers. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Antroduodenal manometry was performed during fasting and gastric feeding with a polymeric diet in patients during mechanical ventilation, weaning, and after detubation. Gastric retention volumes were determined during gastric tube feeding. Motility data were compared with recordings from nine healthy volunteers. During the fasting state, under sedation and morphine, the migrating motor complex in patients was significantly (p < .001) shortened: median 32.0 vs. 101.0 mins in healthy volunteers. During gastric tube feeding, the motility pattern did not convert to a normal postprandial pattern until morphine was discontinued. An interdigestive or mixed interdigestive-postprandial pattern was seen during gastric tube feeding in most patients during morphine administration. Most (94%) of the activity fronts during gastric feeding started in the duodenum. Gastric retention percentages during gastric tube feeding were negatively correlated (r2=.44; p < .01) with antral motor activity. CONCLUSIONS: These data suggest that morphine administration affects antroduodenal motility in mechanically ventilated patients. The gastrointestinal motor pattern involved in impaired gastric emptying in morphine-treated patients is characterized by antral hypomotility and persisting duodenal activity fronts during continuous intragastric feeding. The observed motility patterns suggest that early administration of enteral feeding might be more effective into the duodenum or jejunum than into the stomach of mechanically ventilated patients.

Adult↗
PubMed1998

Mutational scan of the human immunodeficiency virus type 2 integrase protein.

Retroviral integrase (IN) cleaves linear viral DNA specifically near the ends of the DNA (cleavage reaction) and subsequently couples the processed ends to phosphates in the target DNA (integration reaction). In vitro, IN catalyzes the disintegration reaction, which is the reverse of the integration reaction. Ideally, we would like to test the role of each amino acid in the IN protein. We mutagenized human immunodeficiency virus type 2 IN in a random way using PCR mutagenesis and generated a set of mutants in which 35% of all residues were substituted. Mutant proteins were tested for in vitro activity, e.g., site-specific cleavage of viral DNA, integration, and disintegration. Changes in 61 of the 90 proteins investigated showed no phenotypic effect. Substitutions that changed the choice of nucleophile in the cleavage reaction were found. These clustered around the active-site residues Asp-116 and Glu-152. We also found alterations of amino acids that affected cleavage and integration differentially. In addition, we analyzed the disintegration activity of the proteins and found substitutions of amino acids close to the dimer interface that enhanced intermolecular disintegration activity, whereas other catalytic activities were present at wild-type levels. This study shows the feasibility of investigating the role of virtually any amino acid in a protein the size of IN.

Genetic Variation↗
PubMed1997

The solution structure of the amino-terminal HHCC domain of HIV-2 integrase: a three-helix bundle stabilized by zinc.

BACKGROUND: Integrase mediates a crucial step in the life cycle of the human immunodeficiency virus (HIV). The enzyme cleaves the viral DNA ends in a sequence-dependent manner and couples the newly generated hydroxyl groups to phosphates in the target DNA. Three domains have been identified in HIV integrase: an amino-terminal domain, a central catalytic core and a carboxy-terminal DNA-binding domain. The amino-terminal region is the only domain with unknown structure thus far. This domain, which is known to bind zinc, contains a HHCC motif that is conserved in retroviral integrases. Although the exact function of this domain is unknown, it is required for cleavage and integration. RESULTS: The three-dimensional structure of the amino-terminal domain of HIV-2 integrase has been determined using two-dimensional and three-dimensional nuclear magnetic resonance data. We obtained 20 final structures, calculated using 693 nuclear Overhauser effects, which display a backbone root-mean square deviation versus the average of 0.25 A for the well defined region. The structure consists of three alpha helices and a helical turn. The zinc is coordinated with His 12 via the N epsilon 2 atom, with His16 via the N delta 1 atom and with the sulfur atoms of Cys40 and Cys43. The alpha helices form a three-helix bundle that is stabilized by this zinc-binding unit. The helical arrangement is similar to that found in the DNA-binding domains of the trp repressor, the prd paired domain and Tc3A transposase. CONCLUSION: The amino-terminal domain of HIV-2 integrase has a remarkable hybrid structure combining features of a three-helix bundle fold with a zinc-binding HHCC motif. This structure shows no similarity with any of the known zinc-finger structures. The strictly conserved residues of the HHCC motif of retroviral integrases are involved in metal coordination, whereas many other well conserved hydrophobic residues are part of the protein core.

Amino Acid Sequence↗
PubMed1997

Intraoperative search for neuroblastoma by MIBG and radioguided surgery with the gamma detector.

Administration of a tumour-seeking compound labeled with a low-energy isotope and intraoperative screening with the gamma probe (radioguided surgery, RGS) could be useful in reoperations for advanced neuroblastoma when the normal anatomy is altered. A pilot study was performed to test the feasibility of this technique. Five patients underwent six relaparotomies for recurrent stage III or IV neuroblastoma. All had been treated with intensive chemotherapy and/ or metaiodobenzylguanidine (MIBG)-I131 with or without hyperbaric oxygen. Reoperation was performed to achieve near-total (greater than 95%) excision. In all instances, active tumour was seen on the preoperative MIBG scan. Before the operation, a tracer dose of MIBG-I123 was given. At laparotomy, a search was made with the gamma probe for areas of increased activity. The gamma probe correctly identified active neuroblastoma tissue that was seen on the preoperative MIBG scan. There appeared to be a relationship between intensity of radioactivity and degree of maturation on histologic examination. This pilot study shows that RGS with MIBG and intraoperative use of the gamma probe is able to identify recurrent neuroblastoma. Whether this method is able to detect occult tumour and whether RGS will result in better outcome are the subjects of ongoing research.

3-Iodobenzylguanidine↗
PubMed1997

Application of the Mitrofanoff principle in children with severe impairment of bladder function.

Treatment of children with severe impairment of bladder function requires a large-volume, low-pressure reservoir combined with a continent, easily catheterizable valve. The Mitrofanoff principle (MP) appears to meet these requirements. Between 1986 and 1993, the MP was applied in 15 children (4 girls) aged 4 to 14 years. The primary diagnosis was bladder exstrophy in 8 (2 girls), neuropathic bladder in 3 (2 girls), urethral valves in 2, and rhabdomyosarcoma (RMS) in 2. In 10 patients bladder augmentation with an intestinal patch was performed in addition to a Mitrofanoff procedure; in 5 a neobladder and continent appendicostomy were made. One boy with RMS died of distant metastases with a well-functioning appendicostomy and adequate renal function. At 2 to 9 years follow-up of the other 14 patients, 12 have a good result defined as: (1) adequate reservoir capacity; (2) continence; (3) normal renal function; and (4) no hydronephrosis. In 1 exstrophy patient with pre-existing impairment of renal function, further deterioration necessitated frequent catheterization and additional medical treatment. In 1 boy with fulgurated urethral valves, spontaneous micturition became subsequently possible, allowing closure of his appendicovesicostomy. Complications occurred in 10 patients, necessitating reintervention in 7. The MP in combination with the creation of an adequate reservoir gives good results in children with severe impairment of bladder function. Careful attention should be given to patient education regarding emptying of the reservoir. Long-term follow-up of renal function is mandatory.

Adolescent↗
PubMed1997

Malrotation: the postoperative period.

BACKGROUND/PURPOSE: There have been many reports of patients who have persistent gastrointestinal symptoms after undergoing Ladd's procedure. Postoperative return of bowel function in many of these patients seems to be delayed. METHODS: Postoperative return of bowel function after performance of a Ladd's procedure was studied retrospectively in a series of 57 children treated between 1981 and 1994. Excluded were those patients who had a malrotation in combination with an abdominal wall defect, a congenital diaphragmatic hernia, or duodenal atresia. Patients were divided in two groups; one group consisted of patients less than 1 year of age and one group of those 1 year of age and older. RESULTS: Nasogastric tube decompression was necessary for an average of 6.7 days in the first group and 4.3 days in the older children (P = .03). A midgut volvulus delays resumption of bowel function postoperatively. Gastric tube decompression was necessary for 8.6 days (n = 15) compared with only 5.1 days (n = 45) for the group without a volvulus (P = .003, analysis by t test). CONCLUSION: The authors recommend that a central venous line be inserted for feeding purposes when a volvulus is present at operation.

Adolescent↗
PubMed1996

Analysis of the carboxyl-terminal peroxisomal targeting signal 1 in a homologous context in Saccharomyces cerevisiae.

Most peroxisomal matrix proteins contain a carboxyl-terminal tripeptide that directs them to peroxisomes. Within limits, these amino acids may be varied, without loss of function. The specificity of this peroxisomal targeting signal (PTS1) is remarkable considering its small size and its relaxed consensus sequence. Moreover, several peroxisomal proteins have a PTS1-like signal that does not fit the reported consensus sequence. Because many of these PTS1 variants seem to be functional in a species-dependent or protein context-dependent manner, we investigated the PTS1 requirements in a homologous context, using Saccharomyces cerevisiae and endogenous peroxisomal malate dehydrogenase (MDH3). Peroxisomal import of the MDH3-PTS1 variants was tested qualitatively by the ability to complement the Deltamdh3 mutant and quantitatively by subcellular fractionation. We observed efficient import of MDH3 into peroxisomes with a large variety of PTS1 tripeptides. Many of these variants do not fit the observed PTS1 requirements for heterologously expressed proteins, which suggests that additional domains in the protein may be of decisive importance whether or not a certain PTS1 variant is recognized by the components of the peroxisomal import machinery. Because we show that dimerization of MDH3 precedes import into the organelle, these domains are most likely conformational domains.

Blotting, Western↗
PubMed1996

[Iodobenzylguanide-131 therapy as first choice in non-metastasized neuroblastoma].

Three children with a localized pelvic neuroblastoma are presented. Because of progression and clinical signs of compression of adjacent structures therapy was necessary. Targeted radiotherapy with 131I-MIBG was used as the first mode of therapy. This new strategy proved to be feasible, effective and non-toxic. Application of 131I-MIBG as first-line therapy should be considered more often in neuroblastoma patients.

3-Iodobenzylguanidine↗
PubMed1996

Congenital tracheoesophageal fistula: preventing recurrence.

Recurrent tracheoesophageal fistula is a major complication of surgical therapy among children with congenital esophageal atresia and tracheoesophageal fistula. In a consecutive series of 153 patients operated on during a 20-year period in the same institution, only one patient had this complication. The authors believe that adherence to sound surgical principles can lower the risk of fistula recurrence considerably.

Anastomosis, Surgical↗
PubMed1996

Pretreatment with [131I] metaiodobenzylguanidine and surgical resection of advanced neuroblastoma.

Pretreatment with [131I] metaiodobenzylguanidine (MIBG) followed by surgical resection in advanced neuroblastoma (stage 3 and 4) has been studied in relation to resectability, morbidity and mortality, survival rate after two years, control of distant metastasis and serum levels of LDH as prognostic factors. Twenty-one patients with advanced neuroblastoma were primarily treated with MIBG radiotherapy, followed by surgical resection. Sixteen patients had stage 4 disease. Between 2 and 6 courses of MIBG treatment were given per patient. In 17 patients gross complete resection was achieved. Two patients developed complications directly related to the operation, one died as a result of this. The overall mortality was 38%. MIBG therapy resulted in partial response in 13 patients and in stable disease in 8 patients. Two years survival in the group with partial response was 86% and in the group with stable disease 28%. Because of the resulting excellent general condition of the patients the interval between pretreatment with MIBG and surgery could be very short. Follow-up till December 1994 showed that 13 children were alive for 3 to 47 months. Seven had no evidence of disease. Preoperative MIBG de novo treatment in advanced neuroblastoma is equal to induction chemotherapy, but less toxic.

3-Iodobenzylguanidine↗
PubMed1996

Abnormal anatomy of the lumbosacral region imaged by magnetic resonance in children with anorectal malformations.

OBJECTIVE: To investigate the frequency of lumbosacral anomalies, the association with urogenital abnormalities, and the correlation with defaecation pattern by magnetic resonance imaging (MRI). METHODS: A prospective analysis was performed of routine MRI in patients with anorectal malformations. Between 1990 and 1994, MRI was performed in 43 such patients: 31 boys and 12 girls. Twenty four had a high anorectal malformation, 16 had a low anorectal malformation, and three had Currarino's triad. MRI was performed before reconstruction in 26, and postoperatively in 17. Urogenital anomalies were found in 21. RESULTS: Abnormalities of the spinal cord and spine were found with MRI in 20 patients (46.5%); caudal regression syndrome in 10, tethered cord in two, a combination of both in three, and other spinal anomalies in five. These anomalies were found in 30% of the patients with low anorectal malformations, and in 50% with high anorectal malformations. In patients with urogenital malformations, MRI more often showed spinal anomalies (13/21, 62%) than in patients without (7/22, 32%). In high anorectal malformations, defaecation was more often a problem in patients with spinal anomalies (12/15, 80%) than in patients without (2/8, 25%). CONCLUSIONS: Spinal anomalies in the lumbosacral region were found with MRI in 46.5% of patients with anorectal malformations. Since presence of these anomalies seems to be related to clinical outcome, MRI should be performed routinely in all such patients.

Abnormalities, Multiple↗