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Biomedical subjects

S M Kelly

Publications and source records attributed to S M Kelly.

At least 91 records · Page 5Linked to original sources
PubMed1995

Unilateral endoscopic supraglottoplasty for severe laryngomalacia.

OBJECTIVE: To evaluate the effectiveness of unilateral supraglottoplasty in the treatment of children with severe laryngomalacia. DESIGN: Retrospective study. SETTING: Pediatric tertiary referral center. PATIENTS: Eighteen children with severe laryngomalacia. Indications for surgical intervention were obstructive apnea, failure to thrive, cyanosis, and/or cor pulmonale. INTERVENTIONS: Unilateral carbon dioxide laser removal of redundant supraglottic tissue (supraglottoplasty). OUTCOME MEASURES: Evaluation of relief of symptoms, need for subsequent contralateral procedure, and incidence of complications. RESULTS: Three patients required treatment of the opposite side at a later date. There were no complications. Obstructive apnea and weight gain improved in all. CONCLUSIONS: Unilateral supraglottoplasty can be used to treat severe laryngomalacia in most patients. A small percentage of patients will subsequently require a contralateral procedure. Unilateral supraglottoplasty may have less risk of complications than bilateral supraglottoplasty.

Acute Disease↗
PubMed1995

Control of cell volume in oocytes and eggs from Xenopus laevis.

The mechanism by which Xenopus laevis oocytes and eggs survive in hypotonic media was investigated by measuring cell volume (Vc) and intracellular pressure (P(ic)) during osmotic swelling. After 2 hr in 10 mOsm buffer, eggs remained intact, while 60.2 +/- 7.0% of oocytes had burst. Water uptake was proportional to buffer osmolarity in oocytes, but not in eggs. We did not see a regulatory volume decrease in the cells, nor was there any evidence for osmolyte efflux. Oocyte P(ic) increased from 0.27 cm H2O (range 0.14-0.61 cm H2O) to 5.92 cm H2O (range 2.52-7.18 cm H2O, P < 0.001) after 70 min in 20 mOsm buffer. Egg P(ic) in 20 mOsm buffer (0.04 cm H2O, range -0.07 to 0.014 cm H2O) was not significantly different from the value in isotonic (200 mOsm) buffer (0.14 cm H2O, range 0-0.16 cm H2O). The data indicate that Vc in oocytes and eggs is not regulated by either plasma membrane ion transport or the mechanical properties of the vitelline envelope. While oocytes appear to behave as passive osmometers, we speculate that the ability of eggs to maintain volume is determined, in part, by the cytoplasm, in particular by its gel-like nature.

Animals↗
PubMed1995

Detection of Salmonella typhimurium from rectal swabs of experimentally infected beagles by short cultivation and PCR-hybridization.

A rapid and sensitive cultivation and PCR-hybridization procedure for the detection and identification of Salmonella typhimurium was evaluated over a 42-day period with eight experimentally infected beagles. Rectal swabs were taken at several times postinfection, inoculated into selenite-cystine broth, and plated onto Hektoen-Enteric Enteric agar immediately after incubation for 4 and 24 h. PCRs and hybridizations were also conducted with each sample, and the results were compared with those of standard culture techniques to evaluate the efficiency of the PCR-hybridization procedure. The PCR-hybridization procedure was more sensitive than standard culture techniques at each enrichment incubation (P < 0.05). In addition, the PCR-hybridization procedure was significantly better than culture up through 3 days postinfection (P < 0.05). A nonspecific amplified product, relatively close in size to the 457-bp specifically amplified product, did not hybridize to an internal oligonucleotide probe or to a random-primed labeled probe. Subsequent sequence information revealed that the product had very little similarity to the 457-bp product but had significant similarity to an Escherichia coli aldehyde dehydrogenase gene. This study indicated that a cultivation and PCR-hybridization procedure is significantly better than culture for the identification of S. typhimurium. Additionally, the results confirm the importance of determining specificities of PCR products beyond the gel electrophoresis level by hybridization with a specific probe.

Animals↗
PubMed1995

Endoscopic balloon dilatation of duodenal strictures in Crohn's disease.

Endoscopic balloon dilatation of oesophageal and colonic strictures is now widely performed. Duodenal strictures due to Crohn's disease represent a difficult clinical problem as surgical intervention is a major undertaking and recurrences are common. We describe endoscopic balloon dilatation in three patients with obstructive symptoms from duodenal strictures due to Crohn's disease. The procedure appeared safe, was well tolerated and resulted in an excellent symptomatic response. This method is particularly suitable for short duodenal strictures and avoids the need for surgical intervention in this difficult group of patients.

Adult↗
PubMed1995

Respiratory mechanics and gas exchange in postobstructive pulmonary vasculopathy.

Chronic unilateral pulmonary artery ligation induces formation of new bronchial collateral vessels in the affected lung. These vessels form precapillary anastomoses with the pulmonary circulation and the lung is perfused with arterial blood. Inspired gas is diverted to the contralateral lung to maintain the ventilation/perfusion ratio (VA/Q) and gas exchange. This study was designed to determine the mechanism responsible for this shift of ventilation, which has not previously been investigated. We studied six dogs, before and 6 months after ligation of the left main pulmonary artery. We measured pulmonary resistance (RL) and elastance (EL), minute ventilation (VE), O2 consumption (VO2) and CO2 production (VCO2) of the right and left lungs. We also examined the effect of CO2, atropine and isoproterenol on RL and EL. In the lung with ligated pulmonary artery: 1) VE was significantly reduced; 2) RL and EL were increased and were unresponsive to CO2, atropine and isoproterenol; and 3) VO2 decreased more than VCO2 and, consequently, respiratory quotient (RQ) was greater than 1. We conclude that, with chronic pulmonary artery obstruction, ventilation shifts to the contralateral lung because of an increase in RL and EL not related to airway smooth muscle tone.

Animals↗
PubMed1995

The Bateman bipolar prosthesis: a prospective study in primary osteoarthritis.

We present a prospective study of Bateman bipolar prosthesis performed over 5 years in Perth. All patients were treated for primary osteoarthritis using a cementless straight Moore stem and the bipolar acetabular component. Assessment was made at 6-monthly intervals. Harris hip scores were calculated and radiological parameters of inner bearing movement, component migration and proximal osteoporosis were assessed. The group comprised 76 prostheses in 72 patients. The mean Harris hip score at 3 years follow-up was 85, however with a wide range between 55 and 99. A total of 30% of patients at 3 years follow-up had a Harris hip score at less than 70. Twenty-seven per cent of the prostheses at 3 years had restriction of movement at the inner bearing and 43% were judged to have moderate or severe stress shielding around the proximal femur. The clinical results were unpredictable with thigh pain being a significant problem. Because of the unpredictable results we would not advocate the use of the Bateman prosthesis in primary osteoarthritis.

Adult↗
PubMed1994

The DNA recognition subunit of a DNA methyltransferase is predominantly a molten globule in the absence of DNA.

Enzyme-catalysed DNA methylation provides an opportunity for the modulation of protein-DNA recognition in biological systems. Recently we have demonstrated that the smaller of the two subunits of the heterodimeric, cytosine-specific DNA methyltransferase, M. AquI, is largely responsible for sequence-specific DNA recognition. Here we present evidence from a series of NMR, fluorescence and circular dichroism spectroscopy experiments that the DNA binding subunit of M. AquI has the characteristics of a molten globule in the absence of the catalytic machinery. In this metastable state this subunit retains its ability to bind DNA in a sequence-specific manner. We believe this finding offers an insight into the structural flexibility which underpins the mechanism of action of these enzymes, and may provide a possible biological role for molten globules in protein function.

Amino Acid Sequence↗
PubMed1994

The role of tryptophan 97 of cytochrome P450 BM3 from Bacillus megaterium in catalytic function. Evidence against the 'covalent switching' hypothesis of P-450 electron transfer.

The 'Covalent Switching' hypothesis suggests that a strongly conserved tryptophan residue acts as a mediator of electron-transfer flow between redox partners in cytochrome P-450 systems [Baldwin, Morris and Richards (1991) Proc. R. Soc. London B 245, 43-51]. We have investigated the effect of alteration of the conserved tryptophan (Trp-97) in cytochrome P-450 BM3 (P-450 102) from Bacillus megaterium. Replacement of Trp-97 with Ala, Phe or Tyr results in a decrease in the natural haem content and alters the resting spin state of the remaining haem in the purified mutant enzymes. However, kinetic analyses indicate that the mutant enzymes retain high levels of catalytic activity. C.d. and e.p.r. spectroscopy also reveal little alteration in secondary structure or change in the pattern of haem ligation. These findings cast doubt on the covalent switching mechanism of intermolecular electron flow in the P-450s, but indicate that this residue plays a role in the association of the haem prosthetic group.

Alanine↗
PubMed1994

Structural and enzymological analysis of the interaction of isolated domains of cytochrome P-450 BM3.

The interactions of the individually expressed haem- and flavin-containing domains of cytochrome P-450 BM3 have been analysed by enzymological and spectroscopic techniques. Electron transfer between the isolated domains occurs at a much lower rate than that occurring in the intact flavocytochrome. CD spectroscopic studies indicate that the linkage of the domains in intact P-450 BM3 creates haem and amino acid environments suitable for efficient electron transfer from its flavin domain.

Amino Acid Sequence↗
PubMed1994

Product-induced stabilization of tertiary and quaternary structure in Escherichia coli dehydroquinase.

The effects of irreversibly attaching product at the active site of type I dehydroquinase from Escherichia coli have been investigated at the level of the secondary, tertiary, and quaternary structure of the protein by spectroscopic and hydrodynamic techniques. The results agree with the previously identified stabilization of the enzyme but show for the first time that the protein dimer is also stabilized and suggest that the E. coli dehydroquinase subunit may be bilobal.

Circular Dichroism↗
PubMed1994

Ligand-induced conformational states of the cytosine-specific DNA methyltransferase M.HgaI-2.

The interaction of one of the two DNA methyltransferases encoded by the HgaI restriction and modification system, M.HgaI-2, with substrates and substrate analogues is described. Circular dichroism spectroscopy has been used to demonstrate that addition of the methyl donor, S-adenosyl-L-methionine and the inhibitory substrate analogue sinefungin, both induce conformational transitions in the protein in the absence of DNA. Moreover, the addition of DNA is shown to enhance the apparent secondary structure of M.HgaI-2 whilst addition of sinefungin or S-adenosyl-L-methionine reduces apparent secondary structure. The circular dichroism spectrum of the abortive complex between the enzyme, DNA and sinefungin is dominated by the conformational properties of the binary complex of enzyme and sinefungin alone. Addition of a specific oligodeoxynucleotide duplex in which the target cytosine is replaced by a pyrimidinone, leads to a further ligand induced conformational transition as determined by electrophoretic analysis. The addition of sinefungin, or S-adenosyl-L-methionine, to M.HgaI-2 bound to the reactive oligodeoxynucleotide duplex, leads to yet another conformational transition in the protein as determined by the differential susceptibility of ternary and binary complexes to proteolysis. These experiments identify at least six ligand-inducible conformational states of M.HgaI-2 and, in view of the sequence similarity amongst this class of enzymes, suggest that conformational flexibility is a general feature of C-5 cytosine-specific DNA methyltransferases. Moreover, the substitution of the target cytosine by a pyrimidinone mimics the effect of 5-azacytosine incorporation into DNA.

Adenosine↗
PubMed1994

Isolation of Helicobacter pylori from feces of patients with dyspepsia in the United Kingdom.

BACKGROUND/AIMS: Epidemiological studies suggest that fecal-oral spread of Helicobacter pylori potentially represents an important route of infection. However, the bacterium has never been isolated from feces of adults in the developed world. This study attempted to isolate H. pylori from stool specimens donated by 36 adults from the United Kingdom who had dyspepsia. METHODS: Fresh fecal samples were obtained and, after centrifugation to harvest bacteria, cultured onto H. pylori selective growth media. Pure colonies of H. pylori were obtained by subculture and were then analyzed using polymerase chain reaction to confirm genotypic identity. RESULTS: H. pylori was isolated from feces in 12 of 25 subjects with dyspepsia proven to be H. pylori-positive at endoscopy and/or 14C urea breath test. Initial bacterial identification was made on the basis of various phenotypic methods. Genotypic confirmation that the bacterium was indeed H. pylori was also made. CONCLUSIONS: This study is the first to conclusively show that H. pylori can be isolated from feces obtained from adults in the United Kingdom. The implication of this finding is that transmission of H. pylori infection by the fecal-oral route is feasible.

Base Sequence↗
PubMed1994

Paternal cyclophosphamide exposure causes decreased cell proliferation in cleavage-stage embryos.

Exposure of the male germ cell to cyclophosphamide during spermatogenesis and sperm maturation can interfere with development of the embryo. When male rats were treated with a chronic low dose of cyclophosphamide for 4 wk there was a dramatic increase in early postimplantation loss in their progeny, characterized by implantation sites selectively lacking in embryonic tissues. The present study was designed to determine the earliest appearance of a paternal effect of cyclophosphamide treatment and to examine whether the embryonic lineage was selectively affected. Male Sprague-Dawley rats were orally dosed for 4-5 wk with saline or 6 mg/kg per day of cyclophosphamide; their progeny were obtained on Days 2, 2.5, 3, 4, and 4.5 of gestation. Paternal cyclophosphamide treatment had no effect on the mean number of embryos per pregnant female. However, as early as Day 3 of gestation, there was a significant decrease in cell number among the embryos sired by cyclophosphamide-treated males, increasing to a greater than 50% decrease in cell number by Day 4. The cell doubling time in embryos sired by treated males (16 h) was longer than that of controls (12 h). This decreased proliferation rate was confirmed by a dramatic decrease in the capacity of both Day 3 and Day 4 embryos sired by cyclophosphamide-treated males to incorporate [3H]thymidine over a 26-h culture period. Cytogenetic analysis in a limited number of blastomeres entering metaphase revealed no evidence of chromosomal abnormalities. Both the trophectoderm and the inner cell mass cells were proportionally decreased in Day 4.5 embryos sired by cyclophosphamide-treated males. Thus, paternal cyclophosphamide exposure affected both cell lineages in the conceptus as early as Day 3 of gestation.

Animals↗
PubMed1994

Hybrid hepatitis B virus core-pre-S proteins synthesized in avirulent Salmonella typhimurium and Salmonella typhi for oral vaccination.

Avirulent salmonellae expressing foreign genes are attractive for use as oral vaccine carriers. To facilitate the stable expression of heterologous genes without conferring antibiotic resistance, a deletion of the asdA1 gene was introduced into Salmonella typhimurium and S. typhi delta cya delta crp mutant vaccine strains. An asd-complementing plasmid expressing hybrid hepatitis B virus nucleocapsid-pre-S (HBcAg-pre-S) particles was constructed. These hybrid HBcAg-pre-S particle genes were stably expressed in S. typhimurium and S. typhi delta cya delta crp mutant vaccine strains in this balanced, lethal host-vector combination. A single oral immunization of BALB/c mice with a recombinant S. typhimurium delta cya delta crp mutant synthesizing hybrid HBcAg-pre-S elicited potentially virus-neutralizing anti-pre-S serum immunoglobulin G antibodies. In addition, serum immunoglobulin G recognizing S. typhimurium lipopolysaccharide was induced. Distribution in tissue after oral immunization was analyzed in one plasmid-strain combination. The recombinant S. typhimurium colonized the gut-associated lymphoid tissue and the spleen and persisted for over 4 weeks, retaining the HBcAg-pre-S expression plasmid. An isogenic virulence plasmid-cured S. typhimurium delta cya delta crp strain expressing the same HBcAg-pre-S gene had reduced immunogenicity for the carried antigen after oral immunization.

Administration, Oral↗
PubMed1994

Increased gastric juice epidermal growth factor after non-steroidal anti-inflammatory drug ingestion.

Epidermal growth factor (EGF), present in saliva and gastric juice, is a potent mitogen and an important element of mucosal defence. Changes in salivary and gastric juice epidermal growth factor in response to non-steroidal anti-inflammatory drug (NSAIDs) ingestion were measured to assess the role of EGF in gastric mucosal adaptation to NSAIDs. Patients with arthritis underwent endoscopy with collection of saliva and gastric juice for EGF measurement, before and two weeks after continuous NSAID ingestion. During this period patients also received either the prostaglandin analogue misoprostol or placebo in addition to their NSAID. In the misoprostol group (n = 5) there was no observed mucosal damage and no change in either salivary or gastric juice EGF. In the placebo group (n = 10) three patients developed erosions. Salivary EGF did not change (mean (SEM) 3.02 (0.54) ng/ml v 2.80 (0.41) ng/ml) but gastric juice EGF increased from 0.42 (0.12) ng/ml to 0.69 (0.14) ng/ml (p < 0.05). This increased EGF could contribute to the increased cellular proliferation observed during NSAID ingestion and may represent an important mechanism underlying gastric mucosal adaptation.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1994

Altered mechanical properties of lung parenchyma in postobstructive pulmonary vasculopathy.

Postobstructive pulmonary vasculopathy (POPV) produced by chronic unilateral ligation of one pulmonary artery, results in perfusion of the pulmonary capillaries with systemic arterial blood. As a consequence, gas exchange occurs primarily in the contralateral nonligated lung. To determine whether the mechanical properties of the lung parenchyma are changed in POPV, we compared five dogs with chronic ligation of the left main pulmonary artery with five control dogs. Separate measurements of left and right lung airway flows, tracheal pressures, and alveolar pressures were made during mechanical ventilation at frequencies between 5 and 40 breaths/min. We calculated pulmonary elastance (EL) and pulmonary (RL), airway (Raw), and tissue (Rti) resistances. At all frequencies, dogs with POPV had higher left (ligated) EL and Rti and lower right (normal) lung Rti but similar EL compared with the respective lungs from control animals. Raw was the same in both lungs. Histology showed visceral pleura thickening and encroachment of new bronchial collaterals and lymphatics on the parenchyma of the ligated lungs. The contralateral lungs were entirely normal. We conclude that in POPV 1) there is an increase, in the ligated lung, of both EL and RL, the latter likely due to histological changes of the lung parenchyma, and 2) there is a reduction of Rti in the contralateral lung.

Airway Resistance↗
PubMed1994

Arytenoid separation for impaired pediatric vocal fold mobility.

Impaired vocal fold motion may result from cricoarytenoid joint fixation, bilateral vocal fold paralysis, or interarytenoid scarring. Traditional surgical techniques have focused on lateralization or resection of the arytenoid for airway improvement. This paper discusses 3 cases of bilateral reduced vocal fold motion of neurogenic cause treated with posterior cricoid grafting to cause a wider resting position of the vocal folds and arytenoids. Airway improvement occurred in all. The voice results have been encouraging. Advantages of this procedure are that the vocal folds are symmetric, there is no vocal fold or joint scarring, and the larynx remains a candidate for electrical pacing when that becomes available. Acoustic and aerodynamic voice results are presented. The results should be considered preliminary.

Arytenoid Cartilage↗