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K Gabriel

Publications and source records attributed to K Gabriel.

33 records · Page 2Linked to original sources
PubMed1996

Nerve growth factor delivery by gene transfer induces differential outgrowth of sensory, motor, and noradrenergic neurites after adult spinal cord injury.

Several neurotrophic factors have been identified that influence neuronal populations during central nervous system development, maturation, and senescence. To examine the responsiveness of the intact and the lesioned adult mammalian spinal cord to neurotrophic factors, primary rat fibroblasts were genetically modified to produce and secrete human nerve growth factor (NGF). These NGF-producing cells were then grafted to nonlesioned or lesioned adult rat spinal cords for periods of up to 1 year in vivo. Robust outgrowth of sensory and noradrenergic neurites was elicited by grafts in the previously nonlesioned spinal cord. Equally robust growth of sensory and noradrenergic neurites was observed in the lesioned spinal cord; in addition, partial sprouting of local motor neurites was elicited in the lesioned spinal cord. Thus, multiple neuritic populations of the adult spinal cord respond to neurotrophic factors by extending neurites, and this responsiveness is maintained and extended after major injury. Nerve growth factor delivered by somatic gene transfer may be a useful means of promoting axon regrowth in the injured spinal cord.

Adrenergic Fibers↗
PubMed1996

Specific function of a G.U wobble pair from an adjacent helical site in tRNA(Ala) during recognition by alanyl-tRNA synthetase.

G.U wobble pairs are crucial to many examples of RNA-protein recognition. We previously concluded that the G.U wobble pair in the acceptor helix of Escherichia coli alanine tRNA (tRNA(Ala)) is recognized indirectly by alanyl-tRNA synthetase (AlaRS), although direct recognition may play some role. Our conclusion was based on the finding that amber suppressor tRNA Ala with G.U shifted to an adjacent helical site retained substantial but incomplete Ala acceptor function in vivo. Other researchers concluded that only direct recognition is operative. We report here a repeat of our original experiment using tRNA(Lys) instead of tRNA(Ala). We find, as in the original experiment, that a shifted G.U confers Ala acceptor activity. Moreover, the modified tRNA(Lys) was specific for Ala, corroborating our original conclusion and making it more compelling.

Alanine-tRNA Ligase↗
PubMed1995

The actinophage RP3 DNA integrates site-specifically into the putative tRNA(Arg)(AGG) gene of Streptomyces rimosus.

The temperate actinophage RP3 integrates site-specifically into the chromosome of Streptomyces rimosus R6-554. The phage attachment site attP and the hybrid attachment sites of the integrated prophage--attL and attR--were cloned and sequenced. The 54nt core sequence, common to all RP3 related attachment sites, comprises the 3' terminal end of a putative tRNA(Arg)(AGG) gene. AttB bears the complete tRNA gene which is restored in attL after integration. A 7.5kb HindIII fragment, bearing attP, was used to construct an integrative plasmid to simulate the integration process in vivo and to localize the phage genes necessary for site specific integration. The int and xis genes were sequenced and compared to other recombination genes.

Amino Acid Sequence↗
PubMed1995

Polarized ion transport during migration of transformed Madin-Darby canine kidney cells.

Epithelial cells lose their usual polarization during carcinogenesis. Although most malignant tumours are of epithelial origin little is known about ion channels in carcinoma cells. Previously, we observed that migration of transformed Madin-Darby canine kidney (MDCK-F) cells depended on oscillating K+ channel activity. In the present study we examined whether periodic K+ channel activity may cause changes of cell volume, and whether K+ channel activity is distributed in a uniform way in MDCK-F cells. After determining the average volume of MDCK-F cells (2013+/-270 microm3; n=8) by means of atomic force microscopy we deduced volume changes by calculating the K+ efflux during bursts of K+ channel activity. Therefore, we measured the membrane conductance of MDCK-F cells which periodically rose by 22.3+/-2.5 nS from a resting level of 6.5+/-1.4 nS (n=12), and we measured the membrane potential which hyperpolarized in parallel from -35.4+/-1.2 mV to -71.6+/-1.8 mV (n=11). The distribution of K+ channel activity was assessed by locally superfusing the front or rear end of migrating MDCK-F cells with the K+ channel blocker charybdotoxin (CTX). Only exposure of the rear end to CTX inhibited migration providing evidence for "horizontal" polarization of K+ channel activity in transformed MDCK-F cells. This is in contrast to the "vertical" polarization in parent MDCK cells. We propose that the asymmetrical distribution of K+ channel activity is a prerequisite for migration of MDCK-F cells.

Animals↗
PubMed1995

Ethylene oxide allergy in children with spina bifida.

BACKGROUND: Allergic reactions to ethylene oxide (EtO-treated products have occurred in several children with myelomeningoceles. OBJECTIVE: The object of this study was to define the prevalence and significance of EtO-specific IgE among the children in our myelomeningocele clinic. METHODS: The study population comprised three groups: children clinic. METHODS: The study population comprised three groups: children with myelomeningoceles, chronically ill controls (defined as children who had undergone at least three major operations), and well-child controls. Serum specimens were collected from each child, and a commercially available ELISA designed to identify IgE directed against both EtO and latex was performed on the specimens. RESULTS: Seventeen of 75 (23%) children with myelomeningoceles had antibodies directed against EtO, as did 1 of 26 (4%) chronically ill controls. None of the 25 well controls had detectable levels of anti-EtO IgE. Children with antibodies directed against EtO were more likely to be atopic (p = 0.007) and to have a shunt (p = 0.021) and were markedly more likely to have antibodies directed against latex (p = 0.001). On average they had undergone more shunt revisions and other operations than had children without anti-EtO antibodies. CONCLUSION: During the period of study no child had anaphylaxis thought to have been due to EtO exposure.

Adolescent↗
PubMed1995

Latex allergy in children with spina bifida.

We studied the prevalence of latex-specific IgE among the children in our myelomeningocele clinic and several groups of controls using skin tests, a commercially available ELISA and an in-house RAST. Thirty-nine of 83 (47%) children with myelomeningocele had antibodies directed against latex as did 6 of 40 (15.7%) chronically ill controls, 4 of 105 (3.8%) medical controls and 2 of 75 (2.7%) well controls. Within each study group the likelihood of a positive skin test increased with the number of operations the subject had undergone. Children with myelomeningocele were much more likely to have antibodies to latex than were chronically ill controls with similar surgical histories. A retrospective chart review of 18 years and a total of 646 operations disclosed only one episode of intraoperative anaphylaxis which appeared to be related to latex within our study group.

Adolescent↗
PubMed1994

Distinctive acceptor-end structure and other determinants of Escherichia coli tRNAPro identity.

The previously uncharacterized determinants of the specificity of tRNAPro for aminoacylation (tRNAPro identity) were defined by a computer comparison of all Escherichia coli tRNA sequences and tested by a functional analysis of amber suppressor tRNAs in vivo. We determined the amino acid specificity of tRNA by sequencing a suppressed protein and the aminoacylation efficiency of tRNA by examining the steady-state level of aminoacyl-tRNA. On substituting nucleotides derived from the acceptor end and variable pocket of tRNAPro for the corresponding nucleotides in a tRNAPhe gene, the identity of the resulting tRNA changed substantially but incompletely to that of tRNAPro. The redesigned tRNAPhe was weakly active and aminoacyl-tRNA was not detected. Ethyl methanesulfonate mutagenesis of the redesigned tRNAPhe gene produced a mutant with a wobble pair in place of a base pair in the end of the acceptor-stem helix of the transcribed tRNA. This mutant exhibited both a tRNAPro identity and substantial aminoacyl-tRNA. The results speak for the importance of a distinctive conformation in the acceptor-stem helix of tRNAPro for aminoacylation by the prolyl-tRNA synthetase. The anticodon also contributes to tRNAPro identity but is not necessary in vivo.

Amino Acyl-tRNA Synthetases↗
PubMed1994

Oscillating activity of a Ca(2+)-sensitive K+ channel. A prerequisite for migration of transformed Madin-Darby canine kidney focus cells.

Migration plays an important role in the formation of tumor metastases. Nonetheless, little is known about electrophysiological phenomena accompanying or underlying migration. Previously, we had shown that in migrating alkali-transformed Madin-Darby canine kidney focus (MDCK-F) cells a Ca(2+)-sensitive 53-pS K+ channel underlies oscillations of the cell membrane potential. The present study defines the role this channel plays in migration of MDCK-F cells. We monitored migration of individual MDCK-F cells by video imaging techniques. Under control conditions, MDCK-F cells migrated at a rate of 0.90 +/- 0.03 microns/min (n = 201). Application of K+ channel blockers (1 and 5 mmol/liter Ba2+, 5 mmol/liter tetraethylammonium, 100 mumol/liter 4-aminopyridine, 5 nmol/liter charybdotoxin) caused marked inhibition of migration, pointing to the importance of K+ channels in migration. Using patch-clamp techniques, we demonstrated the sensitivity of the Ca(2+)-sensitive 53-pS K+ channel to these blockers. Blockade of this K+ channel and inhibition of migration were closely correlated, indicating the necessity of oscillating K+ channel activity for migration. Migration of MDCK-F cells was also inhibited by furosemide or bumetanide, blockers of the Na+/K+/2Cl- cotransporter. We present a model for migration in which oscillations of cell volume play a central role. Whenever they are impaired, migration is inhibited.

Animals↗
PubMed1993

Association of tRNA(Gln) acceptor identity with phosphate-sugar backbone interactions observed in the crystal structure of the Escherichia coli glutaminyl-tRNA synthetase-tRNA(Gln) complex.

We isolated several mutants with nucleotide substitutions in alanine tRNA (tRNA(Ala)) that resulted in glutamine tRNA (tRNA(Gln)) acceptor identity in Escherichia coli. These substitutions were in three regions of tRNA structure not previously associated with tRNA(Gln) acceptor identity. Only the phosphate-sugar backbone moieties of these nucleotides interact with the enzyme in the previously determined X-ray crystal structure of the complex between tRNA(Gln) and glutaminyl-tRNA synthetase. We conclude that these sequence-dependent phosphate-sugar backbone interactions contribute to tRNA(Gln) identity, and argue that the interactions help communicate enzyme recognition of the anticodon to the acceptor end of the tRNA and the catalytic center of the enzyme.

Amino Acyl-tRNA Synthetases↗
PubMed1989

Efficacy of debridement and primary closure of contaminated wounds: a comparison of methods.

Proper management of highly contaminated traumatic wounds frequently requires delayed primary closure of healing by secondary intention to prevent subsequent infection. This animal study compares the efficacy of various wound debridement methodologies to prevent infection following primary closure of treated contaminated wounds. Forty-four Sprague-Dawley rats with uniform, paravertebral incisions were studied. Each wound was inoculated with a standard amount of Staphylococcus aureus bacteria and allowed to remain open for two hours. Each wound was treated before wound closure by one of four debridement methods: (1) surgical scrubbing, (2) high-pressure irrigation, (3) ultrasonication, or (4) soaking. The control animals' wounds were closed without debridement. At 7 days, each animal was evaluated for the presence of gross infection and wound induration. Ultrasound, with a 25% incidence of gross infection, compared with irrigation (75%), scrubbing (82%), and soaking (89%) provided significant protection from subsequent abscess formation. The control group uniformly developed infection (100%). The average amount of induration after ultrasonication (1.35 +/- 0.56 cm) was also significantly less than irrigation (2.07 +/- 0.75 cm), scrubbing (1.95 +/- 0.34 cm), and soaking (1.73 +/- 0.22 cm). Our data demonstrate that ultrasonic wound debridement has exciting potential as a new debridement technique for contaminated traumatic wounds.

Animals↗
PubMed1989

[Palindromic rheumatism].

49 cases of palindromic rheumatism with a follow-up of 25 years, are reported. More than half of the patients (58%) had their first symptoms between the age of 20 and 39. The knee was the joint the most frequently affected. Five patients had later a rheumatoid arthritis, one had a psoriatic rheumatism, one a cutaneous vasculitis and one had a sero-negative spondylarthropathy. Two patients were completely cured.

Adult↗
PubMed1988

Effect of corticosteroid administration in ischemia--ischemic injury.

In order to study the preservation of ischemic tissue, an in vivo end-artery model was designed using the rabbit ear. Ear surface-area necrosis and ear edema were quantitatively evaluated for 14 postoperative days in a total of 107 rabbits. The LD50 of ischemic injury was determined by effecting 8, 10, and 12 hours of circulatory arrest. Using a 12-hour ischemic interval in this model, methylprednisolone decreased edema formation (p less than 0.01) and dramatically halted the progression of ischemic injury to necrosis (p less than 0.05) when administered within 5 hours after the onset of ischemia and continued for 3 postoperative days. A single perioperative dose of methylprednisolone was ineffective in decreasing edema formation and preserving tissue. Administration of steroids greater than 5 hours after the onset of ischemia was similarly ineffective even when administered for 3 postoperative days.

Animals↗