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Biomedical subjects

T F O'Brien

Publications and source records attributed to T F O'Brien.

At least 37 records · Page 2Linked to original sources
PubMed1992

Afferent-boundary interactions in the developing neostriatal mosaic.

The caudate-putamen (neostriatum) of the mammalian basal ganglia is composed of two neurochemically distinct compartments termed patch (island, striosome) and matrix that overall contribute to a mosaic organization. In the present study, the distribution of the developmentally regulated extracellular matrix molecule tenascin, as well as several other neural cell adhesion molecules, was examined in the neostriatal mosaic of the early postnatal mouse and compared with tyrosine hydroxylase distribution following partial destruction of the dopaminergic nigrostriatal projection. During normal neostriatal development, tenascin is most dense within the matrix compartment and highly concentrated in boundaries around patches. This pattern is apparent on embryonic day 18, and for the most part disappears by postnatal day 12. Tenascin immunoreactivity is altered in the neostriatum following lesions of the nigrostriatal pathway in the first postnatal week revealed by an overall reduced expression of this molecule and a marked reduction in tenascin staining of boundaries at the interface of tyrosine hydroxylase-rich patch and tyrosine hydroxylase-poor matrix compartments. When compared to tyrosine hydroxylase immunoreactivity, other cell adhesion molecules tested failed to show altered intensities and patterns of immunoreactivity within the neostriatum after similar lesions. Reduced levels of tenascin in the lesioned neostriatum, in register with altered levels of tyrosine hydroxylase immunostaining of dopaminergic inputs, suggests that axons may affect the expression of particular recognition molecules in their target structures. The fact that boundaries are malleable can be related to afferent-induced plastic events in the differentiation of cellular elements in the developing nigrostriatal system.

Animals↗
PubMed1992

Extragenital metastases to uterine leiomyomata. A case report.

Malignant extragenital neoplasms with metastases to the uterus are not common, and involvement of a uterine leiomyoma by an extragenital tumor is rare. A case of an infiltrating ductal carcinoma of the breast occurred, with widespread metastases that included a uterine myoma. This entity can be confused with a bizarre or symplastic leiomyoma.

Adult↗
PubMed1992

Therapeutic and epidemiologic recommendations to reduce the spread of type-I beta-lactamase resistance.

The objectives of this United States Consensus Panel meeting were to evaluate the effectiveness of current surveillance systems for the detection of bacterial resistance as well as to formulate recommendations that can assist hospitals in determining actions that should be taken when a resistance problem is detected. These recommendations may be particularly helpful in controlling the emergence and spread of type-I beta-lactamase resistance. Numerous case reports of antimicrobial resistance among Enterobacter species, Pseudomonas aeruginosa, and other Gram-negative nosocomial pathogens known to produce type-I beta-lactamases have appeared in the literature since the introduction of the newer "third-generation" cephalosporins. The widespread use of these newer antimicrobial agents, often selected as standard therapy for serious hospital-acquired infections, has been associated with a corresponding increase in resistance to them. The failure of hospitalwide surveillance methods to describe the scope of this problem, especially among the most critically ill patients, may have resulted in a false sense of security among some infectious disease specialists and clinicians prescribing these antimicrobials as empiric therapy. High-level resistance in individual hospital units may be masked in hospitalwide antibiograms. A variety of conclusions and recommendations were formulated based on the collective experiences of the Consensus Panel members. Microbiology laboratories must make it a high priority to identify markers that will assist in rapidly identifying resistant organisms. Cooperative efforts are needed among users of commercial and automated microbiology test instruments to standardize results and to improve quality control, thereby making the data more directly comparable between laboratories.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents↗
PubMed1991

Gly-238-Ser substitution changes the substrate specificity of the SHV class A beta-lactamases.

The SHV-type beta-lactamase SHV-2A is related to SHV-1 by a Gly-238-Ser replacement. Strains carrying SHV-2A are resistant to the third generation cephems cefotaxime and ceftizoxime, whereas those that carry SHV-1 are sensitive to these drugs. We present a kinetic analysis of a SHV-1 and SHV-2A enzymes, with the goal of gaining insight into the role of residue 238 in hydrolyzing cefotaxime and ceftizoxime. SHV-2A shows altered kinetic properties for a number of other cephems that also have heterocyclic side chains at the amino position of the 7-aminocephalosporanic acid nucleus (R1 side chain), including a significantly higher kcat/Km than does SHV-1 for cephaloridine, cephalothin, and cefotiam. Two cephems with straight chain R1 substitutions, cephalosporin C and cephacetrile, are not hydrolyzed more efficiently by SHV-2A. These results indicate that the Ser-238-Gly substitution increases the affinity toward cephems with a heterocyclic ring in the R1 side chain. In addition, the data for ampicillin and benzylpenicillin show that addition of a nitrogen to the second carbon of the R1 side chain of a penem results in a lower kcat/Km for SHV-2A relative to SHV-1. These data strongly suggest that the previously proposed hydrogen bond formation between Ser-238 and the second carbon nitrogen of cefotaxime is not an important factor in hydrolysis by SHV-2A. We propose that the Gly-238 to Ser-238 replacement in SHV-2A has altered the hydrophobic pocket so that it can better accommodate cephems with bulky R1 side chains.

Amino Acid Sequence↗
PubMed1991

Nosocomial spread of an amikacin resistance gene on both a mobilized, nonconjugative plasmid and a conjugative plasmid.

Resistance to amikacin among members of the family Enterobacteriaceae at a hospital in Venezuela rose from 2% in 1979 to 5% in 1984 and 10% in 1985 as amikacin usage rose 20-fold to exceed gentamicin usage. Resistance to gentamicin remained at 25 to 27%. We examined the plasmids from 21 isolates obtained in 1984 and 1985. Nine of eleven in 1984 and three of ten in 1985 carried aacA and sul on a 3.8-kb BamHI fragment of pBWH300, a 10.4-kb nonconjugative plasmid that had been mobilized into strains of six species by at least two different coresident conjugative plasmids. Six 1985 isolates of two species carried these genes on a similar BamHI fragment of the 104-kb conjugative plasmid pBWH303. One isolate in 1984 and one in 1985 carried the 69-kb conjugative plasmid pBWH301, which had aacA as the promoter-proximal gene of an operon that also encompassed the cat and aadB resistance genes. Another conjugative plasmid, pBWH302, was found in a single isolate. It carried a different aacA allele on the functional transposon Tn654, which appeared to be closely related to Tn1331, a transposon previously isolated in Argentina and Chile. Increased selection may thus have led to dissemination of an endemic aacA allele on two endemic plasmids, one spread by mobilization, with occasional intrusion of additional aacA alleles from outside.

Alleles↗
PubMed1990

The carriage of Escherichia coli resistant to antimicrobial agents by healthy children in Boston, in Caracas, Venezuela, and in Qin Pu, China.

BACKGROUND AND METHODS: The healthy members of a community represent its largest reservoir of bacteria resistant to antimicrobial agents. We compared the resistance to eight agents of Escherichia coli in stool samples from untreated, healthy children in cities on three continents. RESULTS: When screened by a selective method that detected 1 resistant colony in 10,000 colonies, nearly half the children in Boston (18 of 39) had no resistant colonies--a finding consistent with the findings of other surveys performed in developed countries. However, all but 1 of 41 children screened in Caracas, Venezuela, and all but 2 of 53 in Qin Pu, China, carried resistant strains. Only 1 child in Boston but 25 in Caracas and 34 in Qin Pu carried strains resistant to trimethoprim. None of the children in Boston or Caracas but 17 in Qin Pu carried strains resistant to gentamicin. Among 10 colonies selected randomly from each stool sample, the average frequency of resistance in Caracas was 3.6 times greater than in Boston, and that in Qin Pu was 5.3 times greater. There was resistance to five or more antimicrobial agents in 20 percent of the Qin Pu strains and in 6 percent of the Caracas strains but in none of the Boston strains. CONCLUSIONS: In addition to clinical isolates, as reported previously, the bacteria that colonize health children in the community may be resistant far more often in some regions than in others. A low rate of carriage of antimicrobial resistance in the community should become a public health goal.

Anti-Bacterial Agents↗
PubMed1990

Boundaries during normal and abnormal brain development: in vivo and in vitro studies of glia and glycoconjugates.

This paper focuses on transient boundaries of glia and glycoconjugates during development of the mouse central nervous system (CNS). Lectin-bound glycoconjugates, glial fibrillary acidic protein, and the J1/tenascin glycoprotein are distributed coextensively within boundaries around developing substructural arrangements (e.g., developing nuclei, and at a finer level, somatosensory cortical "barrels" related to individual facial vibrissae) throughout the CNS during pattern formation events. Electron microscopy has shown that the J1/tenascin glycoprotein, for example, is present in immature astrocytes, on glial and neuronal plasma membranes, and within the pericellular space that could be extracellular matrix (ECM). The findings presented on the expression of this well-characterized ECM molecule suggest that previously described glial and glycoconjugate boundaries reported by our group are in part composed of specific recognition molecules. The J1/tenascin glycoprotein, a chondroitin sulfate-containing antigen termed the 473 proteoglycan, and the adhesion molecule on glia are expressed within discrete boundary regions and associated axonal pathways. There, they may sculpture fine aspects of functional cytoarchitectonic arrangements and help guide axons to specific targets. The expression and developmental regulation of glycoproteins such as J1/tenascin may thus be integral events during pattern formation and synaptogenesis in the CNS. The presence of abnormal glial arrangements and glycoconjugate boundaries in the cortices of the genetic mutant mouse reeler, and findings on plasticity of boundaries following various perturbations, suggest that boundary expression is controlled by both genetic and epigenetic factors. Some future directions for studying developmental boundaries, including use of cultured explants for in vitro "bioassays," are also discussed.

Aging↗
PubMed1988

Glycoconjugate boundaries during early postnatal development of the neostriatal mosaic.

The dispositions of galactosyl-containing glycoconjugates were studied during postnatal development of the caudate putamen in mice. The binding of the lectin peanut agglutinin, which has an affinity for galactosyl B-1,3 N-acetylgalactosamine residues, was compared to acetylcholinesterase staining and tyrosine hydroxylase immunoreactivity in the immature and adult neostriatum. The binding of peanut agglutinin conjugated to horseradish peroxidase, in sections that were processed for peroxidase histochemistry, was extremely pronounced in the neostriatum through the first postnatal week and constituted ringlike or polygonally shaped structures, which, overall, produced a variegated mosaic. These structures consist of outer rims of dense lectin-associated reaction product surrounding lightly labeled centers. Lectin delineations of the neostriatal mosaic are no longer visible in the second postnatal week. When adjacent sections were processed for lectin binding or acetylcholinesterase histochemistry, the dense lectin binding sites represented borders of acetylcholinesterase-rich and -poor zones. The distribution of dense patches of tyrosine hydroxylase immunoreactive fibers and terminals also coincides with the acetylcholinesterase-rich zones during the same times, and thus the glycoconjugate-delineated boundaries can also be directly compared with the distribution of nigrostriatal dopaminergic projections. The findings presented here represent the first demonstration of a probe that recognizes apparent borders of neostriatal compartments during a limited period of development. They are consistent with previous observations made on transient glycoconjugate "hidden boundaries" during development of other central nervous system structures, including the somatosensory cortical barrel field, and thalamic and brainstem nuclei (Cooper and Steindler, '86a,b; Steindler and Cooper, in press). In those studies, glia were shown to be the major source of glycoconjugate-associated patterns, and thus, glia and glycoconjugates that they synthesize during pattern formation events may be involved in the formation and stabilization of neurochemically distinct components of the neostriatal mosaic.

Acetylcholinesterase↗
PubMed1988

Functional and structural map of pLST1000: a multiresistance plasmid widely distributed in Enterobacteriaceae.

pLST1000, an 80-kb plasmid found in Enterobacteriaceae in North and South America, harbors the aadB and several other resistance genes. We suggested earlier that, because of its widespread distribution, pLST1000 could act as a carrier plasmid, bringing the aadB gene to new locations. This paper presents the restriction enzyme recognition site and functional map of the plasmid. The resistance genes lie in a discreet region. The aadB and aadA genes form an operon with the aadB gene promoter proximal. This operon is flanked by bla-TEM and bla-OXA2 genes, the former located in a functional Tn3-like transposon. This arrangement is similar to that of relatives of the transposon TN21, where additional resistance genes are precisely inserted in recombinational "hot spot" sequences that flank the aadA gene. We were not able to demonstrate transposition of the aadB gene in Escherichia coli. A sul gene and mer operon lie beyond the bla-OXA2 gene. The transfer genes form a single region, defined by insertions of Tn5-132 that give the Tra- phenotype.

Drug Resistance, Microbial↗
PubMed1987

Abnormal glial and glycoconjugate dispositions in the somatosensory cortical barrel field of the early postnatal reeler mutant mouse.

During early postnatal development in reeler mutant mice, lectin binding delineates prospective abnormal barrels as they will appear in the adult mutant somatosensory cortex. Glial fibers also may be more condensed within fascicles in developing reeler barrels. These fibers also appear to be misaligned, coursing predominantly in the tangential plane within the abnormal reeler barrel sides as opposed to having a radial orientation as seen in normal mouse barrels. The thalamic barreloid complex, however, reveals a disposition of glycoconjugates that is completely normal in reeler. Thus, there are anomalies in glia and associated glycoconjugates during mainly cortical development in the reeler mutant mouse that might be related to the primary action of the abnormal gene.

Animals↗
PubMed1987

Loss of OmpC porin in a strain of Salmonella typhimurium causes increased resistance to cephalosporins during therapy.

Minimal inhibitory concentrations of cephalosporins for a strain of Salmonella typhimurium from one patient increased severalfold after starting therapy with cephalexin. The first isolate with increased resistance (S20323) and an earlier, less resistant isolate (S17069) each had a TEM-1 beta-lactamase with similar Vmax and Km values. Intact cells of S20323 grown in a high osmolality medium hydrolyzed cephalosporin substrates much more slowly than did intact cells of S17069 at low substrate concentrations, a result indicating slower diffusion of cephalosporins into S20323. In low osmolality media, S17069 produced both OmpF and OmpC porins; S20323 produced only OmpF porin. In high osmolality media with osmotic activity similar to that in the patient's tissues, synthesis of the OmpF porin was repressed in both strains and left S20323 with undetectably low levels of any porin. The increased beta-lactam resistance in S20323 is apparently a consequence of the loss of the OmpC porin.

Adult↗
PubMed1986

Resistance to antibiotics at medical centres in different parts of the world.

The diameters of the zones of inhibition of consecutive clinical isolates around antibiotic susceptibility test discs at medical centres in different parts of the world were computer filed and analysed by a series of programs that evaluate test quality and compare results. Percentages of isolates resistant to ampicillin at 18 centres ranged from 16 to 73 for Escherichia coli and from 3 to 56 for Proteus mirabilis. Percentages resistant to chloramphenicol ranged from 2 to 48 for E. coli, from 5 to 52 for Klebsiella pneumoniae, and from 8 to 67 for Serratia marcescens. Gentamicin resistance did not exceed 4% at any of 18 centres and was less than 1 at 14 of them for isolates of E. coli, while K. pneumoniae showed less than 2% resistance at six centres but averaged 22% at another eight. Multi-resistant isolates were ten-fold more frequent at eight centres than at the remaining six. Too few centres were sampled to characterize individual countries except in the United States where resistance seemed generally less prevalent.

Anti-Bacterial Agents↗
PubMed1986

Molecular evolution, species distribution, and clinical consequences of an endemic aminoglycoside resistance plasmid.

During the first 6 years after appearing in one hospital, a 92-kilobase conjugative plasmid, pBWH1, which encoded resistance to chloramphenicol and sulfonamides and determined TEM-1 beta-lactamase and 2''-aminoglycoside nucleotidyltransferase, underwent a variety of molecular changes. It was most prevalent initially in isolates of Klebsiella pneumoniae, then in isolates of Serratia marcescens, and finally, after nearly disappearing, in isolates of Enterobacter cloacae. Evolutionary changes in the plasmid did not account for its shifts in species distribution, since the original molecule was found in isolates of each species. The late resurgence of pBWH1 occurred after a copy of its original molecule entered a distinctive ornithine decarboxylase-negative strain of E. cloacae, new to the hospital. The resulting transconjugant strain, chromosomally resistant to topical silver salts and to cephalosporins, and with the addition of pBWH1-encoded aminoglycoside resistance, spread in the hospital by causing an outbreak of sepsis in the burn unit, where these were commonly used antibacterial agents. Thus, an endemic plasmid became prevalent in a new host species because one of its genes supplemented the fitness of an uncommon strain of the species for a particular clinical niche.

Aminoglycosides↗