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Biomedical subjects

A Gilbert

Publications and source records attributed to A Gilbert.

At least 19 recordsLinked to original sources

Hartmann's boutonnière: an anatomical study of digital neural loop penetrations in the palm.

We found neural loop penetrations by digital arteries in 47 of 51 dissected palms. They were classified into four types according to morphology. The most frequent type was observed in the proper digital nerves of the second to fourth interdigital spaces just after branching from the common digital nerves. If neural loop penetrations are not carefully identified at operation they may be damaged and therefore it is important for hand surgeons to recognize the existence of these structures.

Cadaver

Direct demonstration of the endocytic function of caveolae by a cell-free assay.

The endocytic function of caveolae was challenged by taking advantage of a cell-free assay directly measuring the detachment of receptor-containing vesicles from isolated plasma membranes. Plasma membranes from cultured cells surface-labeled with 125I-cholera toxin (segregating in caveolae) were isolated as described previously. Following incubation of these labeled membranes in the presence of nucleotide(s) and cytosol, a significant proportion of the initially membrane-associated radioactivity was released into the incubation medium in sedimentable form (14*10(6 )g). Results of biochemical, morphological, and fractionation analysis of the material containing the released radioactivity directly demonstrated that caveolae are plasma membrane domains involved in an endocytic process and resulting in the formation of caveolae-derived vesicles. In addition, these studies allowed a direct comparison of caveolae- and clathrin-coated pit-mediated endocytosis and reveal that these two processes diverge in terms of kinetics, cytosol and nucleotide requirements as well as in terms of the density and size of the endocytic vesicles formed.

3T3 Cells

Delta F508 CFTR localizes in the endoplasmic reticulum-Golgi intermediate compartment in cystic fibrosis cells.

We have studied the localization of mutant cystic fibrosis transmembrane regulator delta F508CFTR in pancreatic adenocarcinoma cells (CFPAC), which naturally express the mutant protein. Our goal was to investigate whether delta F508CFTR is strictly retained in the endoplasmic reticulum (ER) or alternatively whether it can be transported beyond the ER and reach the endoplasmic reticulum-Golgi intermediate compartment (ERGIC). This compartment, defined by the presence of the 53-kDa protein ERGIC-53, was identified by subcellular fractionation and by immunofluorescence. Part of the delta F508CFTR population and ERGIC-53 showed similar distributions in membrane fractions analyzed on Nycodenz density gradients. Both proteins were present in density fractions distinct from the ones containing the ER marker proteins calnexin and Sec61. Immunofluorescence microscopy of CFPAC cells revealed some colocalization of delta F508CFTR with ERGIC-53. Following incubation of CFPAC cells at 15 degrees C, a condition known to block ER to Golgi transport, both ERGIC-53 and delta F508CFTR subcellular localizations were altered. By contrast, this temperature shift had no effect on the localization of the ER marker Sec61. Our observations indicate that the abnormal protein delta F508CFTR can leak out of the ER and reach the ERGIC. These results support the idea that this intermediate compartment plays a role in the trafficking events leading to retention and finally degradation of the misfolded delta F508CFTR protein.

Adenocarcinoma

Mapping the active site of CD59.

CD59 is a widely distributed membrane-bound inhibitor of the cytolytic membrane attack complex (MAC) of complement. This small (77 amino acid) glycoprotein is a member of the Ly6 superfamily of proteins and is important in protecting host cells from the lytic and proinflammatory activity of the MAC. CD59 functions by binding to C8 and/or C9 in the nascent MAC and interfering with C9 membrane insertion and polymerization. We present data obtained from a combination of molecular modeling and mutagenesis techniques, which together indicate that the active site of CD59 is located in the vicinity of a hydrophobic groove on the face of the molecule opposite to a "hydrophobic strip" suggested earlier. In addition, removal of the single N-linked glycosylation site at Asn18 of CD59 resulted in an enhancement of complement inhibitory activity.

Amino Acid Sequence

[Results of brachial plexus surgery and replacement operations in traumatic brachial plexus birth injury-induced paralysis].

Since the development of microsurgical methods, the timing and concepts of surgery have significantly changed in obstetrical palsies. Because of the high axon regeneration potential in children, early and successful microsurgical reconstruction of the brachial plexus provides very encouraging results. Such successful nerve regeneration is the basis for secondary surgery which aims at complete restoration of function of the upper limb.

Arm

Direct measurement of clathrin-coated vesicle formation using a cell-free assay.

Factors controlling the last stages of clathrin-coated vesicle formation were investigated using an assay allowing direct measurement of the detachment of these vesicles from the plasma membrane. Plasma membranes from cultured cells surface-labelled with 125I-alpha2-macroglobulin (a ligand that preferentially associates with clathrin-coated pits) were isolated by sonication of cells attached to a poly-L-lysine-coated substratum and incubated in the presence of nucleotide(s) +/- cytosol. A significant proportion of the membrane-associated radioactivity was released into the incubation medium in sedimentable form (14x10(6)g). The nucleotide and ligand specificities of this process together with the results of a series of biochemical, morphological and gradient analyses, led to the conclusion that measurement of the released sedimentable radioactivity provides a direct estimate of the formation of clathrin-coated vesicles from clathrin-coated pits. A morphological analysis of quick-frozen replicas of these membranes indicated that only the last stages of clathrin-coated vesicle formation were studied in the assay. Taking advantage of this cell-free system, we demonstrate that membrane-associated cytosolic factors and GTP-binding proteins, noteably dynamin, play a crucial role. Moreover, although these events can occur in the absence of ATP and Ca2+, optimal conditions for the formation of clathrin-coated vesicles require the presence of ATP, GTP and cytosol.

3T3 Cells

Correction of syndactyly using a dorsal omega flap and two lateral and volar flaps. A long-term review.

The long-term results of a technique for correction of syndactyly are reported. The technique consists of a dorsal omega flap and a palmar anchor forming two palmar and lateral flaps. A long-term review was made of 50 patients with a minimum of 8 years follow-up operated over a period of 10 years. A total of 122 web spaces in simple, complex and syndromic syndactyly were operated on. Most patients achieved satisfactory reconstruction of the web spaces, resulting in a web of good shape. At long-term review, web creep was recorded in eight webs, and skin contractures in three fingers. This study shows the technique to be effective in reconstructing web spaces and in minimizing the prevalence of complications.

Age Factors

Obstetric brachial plexus palsy associated with breech delivery. A different pattern of injury.

Most obstetric brachial plexus palsies are due to rupture of the upper roots in babies whose delivery was complicated by shoulder dystocia. If treated by early exploration and grafting, they have a favourable prognosis. We reviewed 36 babies who had had an obstetric brachial plexus palsy after a breech delivery and found that they had a different pattern of injury; 81% had avulsion of the upper roots. This injury cannot be treated satisfactorily by exploration and microsurgical grafting and carries a considerably worse prognosis for shoulder function.

Birth Injuries

Molecular and cellular mechanisms governing the ligand-specific and non-specific steps of insulin receptor internalization.

The surface events leading to insulin-induced internalization of its specific receptor can be subdivided in three major steps: the first step consists in the surface redistribution of the receptor from the villous to the non-villous region of the cell surface, it is ligand-specific, depends on kinase activation and phosphorylation of tyrosines 1146, 1150 and 1151, and consists in the relief of a constraint immobilizing the receptor on microvilli; the second step is characterized by the shift of the insulin-receptor complex in the plane of the membrane allowing it to get access to the nonvillous domain of the cell surface where internalization gates (clathrin-coated pits) are located; this stage is controlled, at least in part, by the transmembrane domain of the molecule and its flanking amino acids; the third step corresponds to the segregation of the insulin-receptor complex in clathrin-coated pits, this step is relatively non-specific and is governed by well defined signal sequences present in the juxtamembrane domain of the cytoplasmic segment of the b-subunit. These surface events are then automatically followed by the entry of the insulin receptor inside the cells through the formation of clathrin-coated vesicles, in its subsequent association with endosomes which acidic pH allows insulin dissociation from its receptor and the sorting of the receptor and the hormone in different directions: insulin is targetted to lysosomes to be degraded while the receptor is recycled back to the cell surface to be reused. This complex process does not seem to be involved in the transmission of the biological signal of the hormone. Nevertheless, it is initiated and controlled by insulin and results in the intracellular degradation of insulin and in the modulation of the number of surface insulin receptors. Thus, even if it does not directly participate in insulin signaling, insulin receptor internalization plays a crucial role in the control of insulin action.

Animals

Gastrocystoplasty: technical and metabolic characteristics of the most versatile childhood bladder augmentation modality.

The authors report on 23 patients who underwent complex continent urinary reconstructions, made successful by the selection of gastrocystoplasty as the chosen augmentation modality. The mean patient age was 6.1 years, and the mean weight was 17.9 kg. The minimum follow-up period was 1.5 years. The bladder capacity increased from a preoperative mean of 77.8 +/- 52.2 (SD) mL to a postoperative mean of 303.5 +/- 117.4 mL (P < .000001). No adverse effects on renal function or serum electrolyte composition were encountered, and there were no instances of acidosis or alkalosis. Continence was achieved in 91% of patients. In two patients (0.9%), hematuria-dysuria developed; one case was extremely mild. The other occurred only during a period of severe oliguria and resolved after transplantation. Gastrointestinal complications were minimal. Five patients had end-stage renal disease at the time of reconstruction and have since had successful transplantation. Gastrocystoplasty is particularly applicable to the pediatric population because of its unique anatomic and metabolic characteristics, which bestow tremendous versatility.

Acidosis

Hook-nail deformity. Surgical treatment with a homodigital advancement flap.

Sixteen patients presenting 18 hook-nail deformities have been treated by the advancement of a homodigital island flap. With an average follow-up of 31 months; Results were considered good or excellent in seven cases, fair in seven and poor in four. Six cases, although improved, had a marked recurrence of the deformity, six had a partial recurrence and six had almost no recurrence. Patient satisfaction was limited as the finger still had a short nail and a square shape.

Adult

Relative microbial resistance of gastric, ileal and cecal bladder augmentation in the rat.

PURPOSE: Bladder resistance to bacterial infection after gastrocystoplasty, ileocystoplasty and cecocystoplasty was investigated in the rat. MATERIALS AND METHODS: Bladders were infected with Escherichia coli 6 to 13 months after augmentation and urine culture was obtained weekly for 3 months. RESULTS: No differences were observed in the number of infected animals within each group or electrolyte data among groups. The number of animals infected after surgery but before E. coli challenge was lowest in the gastrocystoplasty group. Bladder stones formed only in ileocystoplasty and cecocystoplasty groups. No group had a change in urinary pH. CONCLUSIONS: Gastrocystoplasty may be associated with a lower incidence of spontaneous infection and stone formation. An aggressive infection protocol may have masked differences in susceptibility to infection. Since urinary pH was unchanged after gastrocystoplasty, use of the rat may not be appropriate for augmentation studies.

Animals

Congenital pseudarthrosis of the tibia. Long-term followup of 29 cases treated by microvascular bone transfer.

The authors show that vascularized fibular transplantation is the safest technique to treat congenital pseudarthrosis of the tibia. Results of transplantation in 29 patients reveal that the rate and speed of healing were superior to those of any other published method, and the final outcome at maturity was generally acceptable. In addition, the technique allows secondary lengthening procedures to be done. Various factors, such as age at first fracture, age at operation, gender, and type of fixation, did not appear to influence the outcome significantly.

Adolescent

Obstetrical palsy: early treatment and secondary procedures.

Obstetrical palsy has been described since a long time. Unfortunately, until the last 20 years, few options were available to correct its sequelae. During the last two decades, there has been a regain of interest because of the possibility to microsurgically repair these lesions. Tassin in 1984 demonstrated that babies who have no recovery of the biceps function by three months of age should be operated without delay. At brachial plexus exploration, in the presence of neuroma, nerve grafting is usually necessary. In cases of root avulsion, internal or external neurotization should be performed depending on the severity of the lesions. Physiotherapy and long-term follow-up of these patients are primordial to prevent joint ankylosis and to identify the patients who will benefit from secondary surgery. Our results are presented either after early treatment or after secondary procedures. These results justify aggressive management of obstetrical brachial plexus palsy because of children's great capacity for regeneration and accommodation.

Ankylosis