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Biomedical subjects

A Lee

Publications and source records attributed to A Lee.

At least 613 records · Page 34Linked to original sources

Use of a mouse model to examine anti-Helicobacter pylori agents.

A mouse model of Helicobacter infection of the gastric mucosa was evaluated for in vivo screening of new anti-Helicobacter pylori therapies. The aim of the study was to test antimicrobial agents with known anti-H. pylori effects in humans to validate that similar results were obtained in the mouse model. Specific pathogen-free mice were colonized with H. felis, a cat stomach isolate that has been shown to induce chronic gastritis in gnotobiotic mice. In H. felis-inoculated mice 4 weeks after treatment, only 25% were cleared with erythromycin, 47% with metronidazole, 0% with tetracycline, 70% with amoxycillin, and 25% with bismuth subcitrate. In contrast, triple therapy with metronidazole, amoxycillin, and bismuth subcitrate resulted in 80% eradication, whereas triple therapy with metronidazole, tetracycline, and bismuth subcitrate eradicated the Helicobacter from all the animals. We believe the similarities of these treatments to those reported in the literature for humans warrant the use of this model for the early screening of possible anti-H. pylori therapies, especially as in vitro testing has been found to be so non-predictive of therapeutic success.

Animals↗

Spiral organisms: what are they? A microbiologic introduction to Helicobacter pylori.

The stomach provides a hostile environment to most microorganisms owing to the antibacterial effect of gastric acidity. However, over the period of mammalian evolution a highly specialized group of bacteria has evolved to inhabit the gastric mucosa. The common features of these bacteria that allow survival in the stomach and colonization of their natural ecologic niche, mucus, are a specialized form of motility, microaerophilism, and very high activity of the enzyme urease. Other important adaptations have been the acquisition of sophisticated mechanisms to evade host defences, and in certain cases tissue damage may result. The most important of these usually spiral-shaped bacteria is Helicobacter pylori. It is proposed that this bacterium is the human gastric spirillum that in most persons lives in harmony with its natural host, resulting in asymptomatic infection. However, if as yet undefined conditions are present, serious disease may result-that is, peptic ulceration. A consequence of long-term infection may be atrophic gastritis, which sets the scene for gastric carcinoma. The more the microbiology of the stomach is studied, the more species of Helicobacter are discovered, such as H. mustelae in the ferret, H. felis in cats and dogs, and 'Gastrospirillum hominis' in primates, cats, dogs, and pigs. These other helicobacters provide us with a wide spectrum of animal models of gastroduodenal disease. To understand mechanisms of pathogenesis, it is suggested that systematic study of all members of the genus will identify important colonizing factors and provide a realistic perspective on the putative virulence factors that have been proposed for H. pylori to date.

Animals↗

Improvements in the chain-termination method of DNA sequencing through the use of 7-deaza-2'-deoxyadenosine.

Significant improvements in the quality of DNA sequencing data have been shown when deoxyadenosine triphosphate (dATP) is replaced by 7-deaza-2'-deoxyadenosine triphosphate (c7dATP). The use of c7dATP in conjunction with 7-deaza-2'-deoxyguanosine triphosphate (c7dGTP) further decreases anomalies in electrophoretic mobility which are caused by compressions involving G and/or A residues. This effect is observed for both isotope-based and fluorescence-based sequencing approaches. Replacing dATP with c7dATP also results in a higher degree of uniformity in the frequency of chain termination reactions, when such terminations involve the incorporation of fluorescence-labeled dideoxynucleotides by T7 polymerase. These improvements in the gel-resolution and distribution of chain-terminated DNA products result in higher accuracy in both manual and automated base assignment.

Adenosine Triphosphate↗

Influence of fetal breathing and movements on variability of umbilical Doppler indices using different numbers of waveforms.

Umbilical artery continuous-wave Doppler ultrasound waveforms were obtained from three groups of fetuses in late gestation: during quiescence, fetal breathing movements, and fetal body movements. The coefficients of variation, calculated from three values for each Doppler index, which were derived from one, two, four, six and eight waveforms, decreased as the number of waveforms increased. However, statistical analysis showed no significant improvement in variance when more than four waveforms were used during fetal quiescence and breathing and when more than six waveforms were used during fetal movement. A minimum of six waveforms ensured coefficients of variation less than or equal to 10% even during fetal breathing and fetal movements.

Female↗

Helicobacter pylori-associated gastritis is rare in AIDS: antibiotic effect or a consequence of immunodeficiency?

Helicobacter pylori is the principal cause of type B histologic gastritis. AIDS is associated with increased susceptibility to Gram-negative enteric infections. Using a retrospective study design, we have determined the prevalence of H. pylori-associated histologic gastritis (based on gastric histopathology) in 201 patients with AIDS. These data were compared with H. pylori prevalence rates (based on serology) from healthy HIV-negative, age-matched Australian controls (n = 785) and a cohort (n = 137) of HIV-negative, dyspeptic patients undergoing panendoscopy and antral biopsy, at a community endoscopy center. Twenty-five of 201 (12.5%) patients with AIDS had histologic gastritis and, of these, six (25%) had H. pylori. The 3% (six of 201) H. pylori prevalence rate in the AIDS patients was significantly less than age-matched HIV-negative controls (22%) p = 0.001 and endoscopy center controls (59%) p = 0.009. The explanation for this unexpectedly low prevalence of H. pylori is not possible from these data. It may be a consequence of antimicrobial therapy. Other potential explanations may include specific HIV-related host factors, including hypochlorhydria or an inadequate mucosal inflammatory response, which may impair successful colonization of H. pylori.

Acquired Immunodeficiency Syndrome↗

Commonly used suture materials in skin surgery.

The ideal suture is strong, handles easily and forms secure knots. It causes minimal tissue inflammation and does not promote infection. It stretches, accommodates wound edema and recoils to its original length with wound contraction. Ideally, it is also inexpensive. Although no single suture material possesses all of these features, proper selection of sutures helps achieve better results in skin surgery. Among the absorbable sutures are catgut and treated catgut (both are used infrequently) and the synthetic sutures, which are designed for good tensile strength, easy handling and low tissue reactivity. Nonabsorbable sutures include silk (now infrequently used) and several synthetic materials designed for elasticity, easy handling, good knot security and minimal tissue irritation.

Absorption↗

Tourniquets.

All tourniquet equipment must be regularly maintained. Cuffs and tubing must be checked for leaks, gauges calibrated regularly and automatic apparatus which depends upon reservoirs of gas must not be allowed to become depleted. A tourniquet is an invaluable piece of equipment when used correctly. Its advantages far outweigh its disadvantages, provided that proper precautions are observed.

Humans↗

Cardiac transplantation at the University of Pittsburgh: 1980 to 1991.

When examining survival rates following cardiac transplantation, it is important to examine the risk factors for both early (30-day) and late (greater than 30-day) survival as they may well be different. Factors affecting early survival appear related more to the preoperative condition of the patient (including degree of pulmonary hypertension) as well as advances that have been made in postoperative care. It is not immediately obvious why gender has such a profound effect on early survival and why primary graft failure rates appear higher in this group. Donor organ factors did not appear to relate to this difference. On the other hand, late survival appears to be influenced mainly by immunologic factors such as panel reactive antibody level and immunosuppressive protocol. A less dramatic effect of transpulmonary gradient appears to have a lasting effect on recipients even when they survive the initial 30-day period. Thus, pulmonary hypertension may have prolonged effects on the cardiac allograft which as yet we do not understand completely. The majority of late mortality is still due to graft atherosclerosis, infection, and acute cellular rejection, the latter 2 occurring most frequently within the first year after transplantation whereas death from graft atherosclerosis becomes most prominent beyond 5 years. Despite persistent improvements in 30-day survival, late survival following cardiac transplantation will only improve with the advent of better tissue matching and improved immunosuppression. The results with FK506, for example, are promising.

Adult↗

Commonly used suturing techniques in skin surgery.

Proper suturing technique is essential for obtaining good cosmetic results and avoiding infection, scarring and poor wound healing. Techniques that must be mastered include good eversion of skin edges, avoiding suture marks, maintaining uniform tensile strength along the skin edges and precise approximation of skin edges. Vertical mattress sutures have the advantage of good wound eversion and closure of dead space. Running continuous sutures can be quickly placed and divide tension equally along the skin edge. Interrupted sutures are more time-consuming but allow more precise wound edge approximation, while subcuticular sutures are useful for avoiding suture marks in conspicuous areas.

Dermatologic Surgical Procedures↗

Compatibility of cefoperazone sodium and furosemide in 5% dextrose injection.

The compatibility of cefoperazone sodium and furosemide in 5% dextrose injection stored at two temperatures was studied. Cefoperazone sodium and furosemide were added to 5% dextrose injection to achieve a cefoperazone concentration of 10 mg/mL and a furosemide concentration of 0.2 mg/mL. The admixture was stored in 100-mL vented i.v. containers in the dark under refrigeration (4 degrees C) and at room temperature (25 degrees C); three containers were stored at each temperature. A 1-mL sample was taken from each i.v. container immediately after preparation and after 1, 2, 5, 10, 15, 20, and 25 days to be inspected visually, checked for pH value, and analyzed by a stability-indicating high-performance liquid chromatographic method. No color change or precipitation was observed in any sample at any time during the study. More than 95% of the initial concentrations of both drugs remained for five days at 4 degrees C but for only two days at 25 degrees C. Cefoperazone sodium was somewhat more stable than furosemide under the same storage conditions for 25 days; however, less than a 2% difference between the drugs was noted. Under the conditions of this study, cefoperazone sodium 10 mg/mL and furosemide 0.2 mg/mL in admixtures in 5% dextrose injection are stable for only two days at 25 degrees C and five days at 4 degrees C.

Cefoperazone↗

Compatibility of cefoperazone sodium and cimetidine hydrochloride in 5% dextrose injection.

The compatibility of cimetidine hydrochloride and cefoperazone sodium in 5% dextrose injection stored at two temperatures was studied. Cimetidine hydrochloride and cefoperazone sodium were reconstituted or diluted with 5% dextrose injection to form an admixture with a cimetidine concentration of 2 mg/mL and a cefoperazone concentration of 5 mg/mL. The admixture was stored in 100-mL vented i.v. containers in the dark at 4 and 25 degrees C; three containers were stored at each temperature. A 2-mL sample was taken from each container after 0.5, 0.75, 1, 6, 12, 24, and 48 hours of storage and visually inspected, tested for pH, and assayed by a stability-indicating high-performance liquid chromatographic method. Triplicate studies were done for each storage condition. At both temperatures, drug concentrations varied by less than 5% during the study period. No color change, precipitation, or cloudiness was observed for any of the solutions under any of the storage conditions. Cefoperazone sodium 5.0 mg/mL and cimetidine hydrochloride 2.0 mg/mL in admixtures in 5% dextrose injection are stable for 48 hours at 4 and 25 degrees C.

Cefoperazone↗

Molecular cloning and expression of a receptor for human tumor necrosis factor.

A human tumor necrosis factor (TNF) binding protein from serum of cancer patients was purified to homogeneity and partially sequenced. Synthetic DNA probes based on amino acid sequence information were used to isolate cDNA clones encoding a receptor for TNF. The TNF receptor (TNF-R) is a 415 amino acid polypeptide with a single membrane-spanning region. The extracellular cysteine-rich domain of the TNF-R is homologous to the nerve growth factor receptor and the B cell activation protein Bp50. Human embryonic kidney cells transfected with a TNF-R expression vector specifically bind both 125I-labeled and biotinylated TNF-alpha. Unlabeled TNF-alpha and TNF-beta were equally effective at displacing the binding of labeled TNF-alpha to TNF-R expressing cells. Northern analysis indicates a single species of mRNA for the TNF-R in a variety of cell types. Therefore, the soluble TNF binding protein found in human serum is probably proteolytically derived from the TNF-R.

Amino Acid Sequence↗

Helicobacter mustelae-associated gastritis in ferrets. An animal model of Helicobacter pylori gastritis in humans.

Gastric Helicobacter mustelae was present in 100% of 11 adult female ferrets (Mustela putorius furo). The high immunoglobulin G antibody levels to H. mustelae in all ferrets showed a significant immune response to the organism. Urease mapping of the ferret stomach indicated that the bacteria heavily colonized the proximal duodenum and antrum and, to a lesser extent, the corpus. The histological gastritis observed coincided with presence of H. mustelae. Superficial gastritis was noted in the oxyntic gastric mucosa, whereas in the distal antrum the chronic inflammatory response occupied the full thickness of the mucosa. In the proximal antrum and transitional mucosa, focal glandular atrophy and regeneration were observed. Seven control specific-pathogen-free ferrets were not colonized with the bacteria, did not have detectable levels of immunoglobulin G H. mustelae antibody, and did not have H. mustelae-associated gastritis. The ferret lacks the polymorphonuclear-cell response seen in active chronic gastritis typically described with Helicobacter pylori gastritis in humans. However, the lesion in ferrets does closely resemble the diffuse antral gastritis seen in a subset of adults with H. pylori gastritis as well as children infected with H. pylori. Like H. pylori, H. mustelae adheres tightly to gastric mucosa. The ferret infected with H. mustelae, in addition to specific-pathogen-free uninfected control ferrets, will make longitudinal studies possible, enabling dissection of multiple host and environmental variables that influence the effect of H. mustelae colonization on progression and severity of gastroduodenal disease.

Animals↗

A small animal model of human Helicobacter pylori active chronic gastritis.

Isolation of a spiral-shaped bacterium closely related to Helicobacter pylori from the cat stomach made it possible to investigate new small animal models of gastric infection. Pure cultures of this bacterium, provisionally named "Helicobacter felis," were fed to germ-free mice. The organism colonized the stomach in large numbers in mucus and deep in the gastric pits and showed the same gastric trophism found with H. pylori. Significant histopathology was seen in all H. felis-infected mice. At 2 weeks postinfection, an acute inflammatory response was seen composed primarily of eosinophils and neutrophils. At 3 weeks, the polymorphonuclear response was more pronounced with large numbers of neutrophils in some areas forming small microabscesses. Lymphocytes also increased in number. By 8 weeks, several relatively large lymphoid nodules were present in the submucosa. Multiple small microabscesses were still present in the pyloric mucosa. This is the first animal model of bacterial gastritis to be described that shows progression from acute inflammation to persistent acute on chronic inflammation (active chronic) as is seen in human infection with H. pylori.

Acute Disease↗

Leptomeningeal cyst: nonenhanced and enhanced computed tomography findings.

Leptomeningeal cyst (a growing fracture of childhood) is well recognized as a rare complication of traumatic skull injuries. The clinical and plain roentgenogram findings have been described previously in the literature. These fractures are commonly associated with encephalomalacic changes of the underlying herniated brain tissue that occurs as part of the pathophysiology of leptomeningeal cyst formation. This is a case report of a leptomeningeal cyst with peripheral enhancement of the herniated issue most likely representing the pia mater, and/or development of a highly vascularized pseudodura. The computed tomography findings pre and postcontrast of a growing fracture of childhood have not been previously reported.

Arachnoid↗

Chromosomal localization of seven members of the murine TGF-beta superfamily suggests close linkage to several morphogenetic mutant loci.

Chromosomal locations have been assigned to seven members of the TGF-beta superfamily using an interspecific mouse backcross. Probes for the Tgfb-1, -2, and -3, Bmp-2a and -3, and Vgr-1 genes recognized only single loci, whereas the Bmp-2b probe recognized two independently segregating loci (designated Bmp-2b1 and Bmp-2b2). The results show that the seven members of the TGF-beta superfamily map to eight different chromosomes, indicating that the TGF-beta family has become widely dispersed during evolution. Five of the eight loci (Tgfb-1, Bmp-2a, Bmp-2b1, Bmp-2b2, Vgr-1) mapped near mutant loci associated with connective tissue and skeletal disorders, raising the possibility that at least some of these mutations result from defects in TGF-beta-related genes.

Amino Acid Sequence↗

Horizontal transmission of Campylobacter jejuni amongst broiler chicks: experimental studies.

Horizontal transmission of Campylobacter jejuni was investigated in campylobacter-free broiler chicks. One hundred and twenty chicks housed individually, were provided with water containing 10(2)-10(9) c.f.u./ml C. jejuni. Colonization was rapid [47 of 73 (64%) positive cloacal cultures within 3 days and 65 of 73 (89%) within 7 days], dependent on C. jejuni strain and inoculum size but independent of chick age. Groups of 5-24 chicks in isolators were exposed to C. jejuni-contaminated water or colonized seeder chicks. Transmission occurred in 2-7 days concurrent with a gradual increase of C. jejuni in litter, water and feed. Environmental samples were culture-negative within 3 days following removal of colonized chicks. Treatment of 1-day-old chicks with adult caecal microbiota did not affect colonization. Treated and control chicks were all C. jejuni-positive within 3 days of seeder challenge.

Animal Feed↗