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Biomedical subjects

T F O'Brien

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

At least 19 recordsLinked to original sources
PubMed1996

Solitary focal demyelination in the brain as a paraneoplastic disorder.

Solitary focal demyelination (SFD) in the brain is an uncommon and poorly understood disorder of uncertain etiology that may represent an intermediate entity between multiple sclerosis and acute disseminated encephalomyelitis. In a few reported cases of SFD, the patient was briefly noted to have a nonneurological malignancy. We studied two patients who had solitary focal lesions in the brain. Utilizing magnetic resonance imaging and tissue biopsy, we found the characteristics of the brain lesions in these two patients to be those of SFD. In our combined experience over the past 10 years, we have encountered no similar brain lesions at our medical center. We found it remarkable that both of these patients also had malignancy outside of the nervous system. One had a seminoma, and the other a lymphoma. We conclude that some cases of SFD in the brain may occur as a paraneoplastic disorder associated with nonneurological malignancies.

Adult↗
PubMed1995

DNA end labeling (TUNEL) in Huntington's disease and other neuropathological conditions.

Deoxyribonucleic acid of cells undergoing apoptosis is cleaved by a calcium-dependent endonuclease into oligonucleosomal-sized fragments. These fragments can be labeled using the enzyme terminal deoxynucleotidyl transferase so that the cells can be visualized immunohistochemically. Few investigators have evaluated this method in disease processes of the human central nervous system. The Tdt-mediated dUTP-biotin nick end labeling (TUNEL) technique has been investigated in preliminary studies of a variety of pathologic conditions of the human brain (e.g., gliomas, traumatic brain injury, Parkinson's disease, Parkinson's-Alzheimer's complex, multisystem atrophy, striatonigral degeneration). We focus, however, on Huntington's disease (HD) because of the availability of well-characterized pathological stages for study, and also because of the neurodegenerative diseases studied to date, only Huntington's disease revealed significant and consistent labeling with this method. This implies a possibly unique nature to the mechanism of cell death in Huntington's disease compared to the other neurodegenerative diseases studied. TUNEL+ neurons were found in Grade 1-4 HD neostriatum, while labeled astrocytes were found predominantly in the Grade 1 and 2 cases studied to date. TUNEL+ cells were also found in glioblastoma multiforme and traumatic brain injury. We conclude that while there appear to be several limitations associated with this technique, it may be useful for identifying both apoptosis and necrosis in certain neuropathological conditions.

Brain Injuries↗
PubMed1995

Hemangioblastoma of the radial nerve: case report.

A case of hemangioblastoma of the right radial nerve is presented. Hemangioblastomas are rare vascular neoplasms characteristically associated with the Von Hippel-Lindau syndrome, in which they are found in the retina, the posterior fossa, and, less often, the spinal cord. Thought of as primary central nervous system neoplasms, hemangioblastomas are rarely found adjacent to the spinal cord involving proximal nerve roots, which represent border zones between the central and peripheral nervous systems. We could find no other report of a pure hemangioblastoma situated this far distally in the peripheral nervous system. The histological findings, immunohistochemistry, and electron microscopic findings of this lesion are discussed. This case supports the hypothesis that hemangioblastoma is not derived from astrocytes, because of the location of this tumor in the peripheral nervous system and glial fibrillary acidic protein negativity.

Aged↗
PubMed1995

Focal brain injury and upregulation of a developmentally regulated extracellular matrix protein.

Tenascin is an extracellular matrix glycoprotein expressed during both normal development and neoplastic growth in both neural and nonneural tissues. During development of the central nervous system (CNS), tenascin is synthesized by glial cells, in particular by immature astrocytes, and is concentrated in transient boundaries around emerging groups of functionally distinct neurons. In the mature CNS, only low levels of the glycoprotein can be detected. The present study demonstrates that following trauma to the adult human cerebral cortex, discrete populations of reactive astrocytes upregulate their expression of tenascin and dramatically increase their transcription of the tenascin gene. The enhanced expression of tenascin may be involved in CNS wound healing, and may also affect neurite growth within and around a brain lesion.

Adult↗
PubMed1995

Meningeal melanocytoma. An uncommon diagnostic pitfall in surgical neuropathology.

OBJECTIVE: To describe the neuropathologic findings in four cases of meningeal melanocytoma, a rare benign melanocytic tumor of the central nervous system. DESIGN: Retrospective analysis of surgical pathology and autopsy material. RESULTS: Grossly, all four tumors were well-circumscribed pigmented lesions, and three of four were attached to dura. Microscopically, the neoplasms were composed of spindle cells with epithelioid foci. Mitoses were not seen and only one case exhibited minimal necrosis. Immunohistochemistry and electron microscopy demonstrated the melanocytic nature of the lesions; all four cases showed S100 protein and neuron-specific enolase staining, and three cases exhibited melanoma-specific antigen staining. Immunostaining for epithelial markers and vimentin was uniformly negative. The single case in which electron microscopy was performed demonstrated premelanosomes. CONCLUSIONS: Meningeal melanocytoma is a benign pigmented neoplasm that can easily be confused with melanoma, especially on frozen section analysis. Practicing surgical pathologists should be aware of this entity.

Adolescent↗
PubMed1994

Detection and surveillance of antimicrobial resistance.

The clinical microbiology laboratory is strategically positioned to recognize changing patterns in bacterial resistance to antimicrobials. This requires the application of accurate testing methods and a methodological survey of drug-resistance patterns among clinically important bacteria. This information can be assembled into comprehensive international databases, using a common format to facilitate monitoring.

Drug Resistance, Microbial↗
PubMed1993

Plasmid diversity in Escherichia coli isolated from processed poultry and poultry processors.

Plasmids of bacteria selected from different bacterial populations because they shared a distinctive antimicrobial resistance phenotype have sometimes had identical restriction fragments. Such identical plasmids are thought to belong to small and thus epidemic clones because the plasmid content of unselected resistant isolates has seemed diverse. To survey this presumed diversity and its implications for the lineage of resistance plasmids we examined the transferability, sizes and EcoR1 restriction fragment sizes of plasmids in both Escherichia coli isolated randomly from poultry raised by 16 growers as they were being processed through two plants and in isolates from the urine of women processing poultry in those plants. Forty two (24%) of 175 resistant isolates from poultry of 16 growers and 9 (26%) of 34 resistant isolates from the poultry processors transferred resistance conjugatively to varied combinations of antimicrobials. No poultry isolate had both the same expressed and the same transferred combination as any processor's isolate. The DNA bands which could be discerned in electrophoresis gels of restricted or unrestricted plasmid extracts of isolates or their transconjugants from 156 of the poultry and 24 of the poultry processors appeared diverse. Pairs of related-appearing plasmids were seen in consecutive isolates of poultry from each of two growers and in one pair from different growers. One set of identical-appearing plasmids was seen in 3 consecutive isolates from poultry of one grower, others in 2 consecutive isolates from a second grower's poultry, in 2 non-consecutive isolates of a third grower's, and in single isolates from poultry of 2 different growers. None of the plasmids from any of the human isolates appeared related to those from any other human isolate or to those of any poultry isolate. These results indicate that resistance plasmids are highly diverse and that all but two of the exceptions to complete diversity in the isolates surveyed here could be ascribed to cross colonization within flocks of individual poultry growers. Also, while none of the plasmids in the poultry isolates appeared ancestral to any of plasmids in the poultry processors' isolates, their diversity indicates that those sampled plasmids would be only a very small fraction of the total number of different plasmids in bacteria colonizing poultry processed at that time or earlier.

Animals↗
PubMed1993

The epidemiology of bacterial resistance to quinolones.

The new fluoroquinolones have been in use for nearly 10 years in the treatment of community- and nosocomially-acquired infections. Resistant clones may be selected during therapy and disseminate if favourable epidemiological conditions prevail. Resistance to the fluoroquinolones is still rare in common pathogens with 97 to 100% of strains remaining susceptible. Resistance has been reported in methicillin-susceptible Staphylococcus aureus, Campylobacter jejuni/coli, Salmonella, Shigella and Escherichia coli. Among nosocomial pathogens, the incidence of fluoroquinolone resistance varies between bacterial species, countries and periods of study, and is dependent on local epidemiological factors and antibiotic policies. The highest incidence of resistance is observed in Serratia and Acinetobacter spp., and particularly in methicillin-resistant S. aureus. Surveillance programmes are needed to follow up trends in resistance to the fluoroquinolones and their possible association with clinical failures.

Anti-Infective Agents↗
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↗