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R L Meyer

Publications and source records attributed to R L Meyer.

At least 19 recordsLinked to original sources
PubMed2005

Duration of smoking abstinence as a predictor for non-small-cell lung cancer survival in women.

BACKGROUND: Previous studies have attempted to investigate the impact of smoking cessation on lung cancer survival but have been limited by small numbers of former smokers and incomplete data. METHODS: Over a six-year period, 5229 patients with non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) were enrolled in a prospective cohort of whom 2052 were former smokers. Patient's characteristics were obtained from medical records and a baseline interview. Vital status was determined through multiple sources. Cox proportional hazards models were used to estimate the effect of smoking abstinence on post-diagnosis mortality. RESULTS: For all patients with NSCLC, the median survival among never, former, and current smokers was 1.4 years, 1.3 years, and 1.1 years, respectively (P < 0.01). Female NSCLC patients had a significantly lower risk of mortality with a longer duration of smoking abstinence (RR per 10 years of smoking abstinence = 0.85; 95% CI: 0.75, 0.97). No effect of smoking abstinence on mortality was observed for women with SCLC or for men with either histologic group. CONCLUSIONS: The identification of smoking history as a prognostic factor in lung cancer survival supports previous research suggesting a direct biologic effect of smoking on survival. However, this effect may vary by sex and type of lung cancer.

Aged↗
PubMed2004

Integration of titrimetric measurement, off-gas analysis and NOx- biosensors to investigate the complexity of denitrification processes.

The denitrification process, namely the reduction of nitrate (NO3-) to nitrogen gas (N2), often cannot be simply modelled as a single step process. For a more complete and comprehensive model the intermediates, particularly nitrite (NO2-) and nitrous oxide (N2O), need to be investigated. This paper demonstrates the integration of titrimetric measurements and off-gas analysis with on-line nitrite plus nitrate (NOx-) biosensors, highlighting the necessity of measuring process intermediates with high time-scale resolution to study and understand the kinetics of denitrification. Investigation of activated sludge from a full-scale treatment plant showed a significant accumulation of NO2-, which appeared to impact on the overall denitrification rate measured as NOx- reduction or N2 production. A different sludge obtained from a lab-scale bioreactor produced N2O instead of N2 as the end product of denitrification. The two examples both illustrate the complexity of denitrification and stress the need for the more versatile and detailed measurement procedures, as presented in this paper.

Bioreactors↗
PubMed2001

Regenerating optic fibers correct large-scale errors by random growth: evidence from in vivo imaging.

Regenerating optic fibers in goldfish make large-scale errors when they invade tectum and subsequently correct these to generate a projection with moderate retinotopic order by 1 month. The behavior of fibers underlying these extensive rearrangements is not well understood. To clarify this, we have imaged optic fibers in living adult goldfish at 2-4 weeks of regeneration. A small number of neighboring retinal ganglion cells were labeled with microinjections of DiI and imaged in the dorsal tectum with a cooled CCD camera on a fluorescence microscope for 5 to 8 hours. Nearly all fibers were simple unbranched processes and had endings that were highly dynamic showing both growth and retraction. Fibers from dorsal retina that normally innervate ventral tectum were frequently observed in dorsal tectum. These ectopic fibers oscillated more frequently between growth and retraction and retracted more often than ventral optic fibers. Like retinotopic fibers, ectopic fibers exhibited net growth but they showed no apparent directional preference toward their retinotopic position. In contrast, large errors along the anterior-posterior axis corresponding to nasal-temporal retina were rare and there was no differential behavior that distinguished these fibers.

Animals↗
PubMed2001

Increased NCAM-180 immunoreactivity and maintenance of L1 immunoreactivity in injured optic fibers of adult mice.

The injury related expression of two axon-growth promoting cell adhesion molecules (CAMs), NCAM-180 which is developmentally downregulated and L1 which is regionally restricted, were compared in optic fibers in the adult mouse. The neuron-specific isoform of NCAM (NCAM-180) is present at very low levels in unlesioned adult optic axons. At 7 days after nerve crush, immunoreactivity was strongly and uniformly increased in optic axons within the nerve and throughout retina. Reactivity in surviving axons had returned to control levels at 4 weeks. To induce regrowth of adult retinal ganglion cell axons retinal explants were placed in culture. Strong NCAM-180 staining was observed on these regenerating optic axons. The neuronal cell adhesion molecule L1 is restricted to retina and to the unmyelinated segment of the optic nerve near the optic nerve head in unlesioned adult animals. Following nerve crush, L1 immunoreactivity was retained within retina and proximal nerve and novel staining was detected in the more distal segment of the optic nerve up to the lesion site where it persisted for at least eight months. The capacity of optic fibers to show increased NCAM-180 immunoreactivity and maintain L1 expression after a lesion may explain why these fibers exhibit relatively good potential for regeneration.

Animals↗
PubMed2001

N-cadherin is involved in axon-oligodendrocyte contact and myelination.

We have analyzed the influence of the calcium-dependent cell adhesion molecule, N-cadherin, on events leading to CNS myelination. Interactions between axons and oligodendrocyte progenitor (OP) cells and the CG4 OP cell line were examined by video-microscopy. OPs cocultured with dorsal root ganglia explants migrated around the culture and formed numerous contacts with axons. The duration of these contacts depended on the morphology of the OP, with OPs containing four or more processes forming long-lasting contacts and OPs with three or fewer processes forming short-termed contacts. Treatment with N-cadherin function blocking peptides approximately halved the duration of contacts made by cells with four or more processes but contact times for cells with three or less processes were unaffected. The L7 cadherin-blocking antibody and calcium withdrawal had similar effects. Contacts with axons regenerating from explants of adult retina, which do not have N-cadherin on their surface was examined. The contact duration of OPs to adult retina axons was short and similar in length to those formed between OPs and dorsal root ganglion axons in the presence of cadherin blocking reagents. Oligodendrocyte myelination was examined in organotypic rat cerebellar slice cultures, taken before myelination at postnatal day 10 and then allowed to myelinate in vitro over 7 days. When incubated with an N-cadherin function-blocking peptide, myelination of Purkinje cell axons was reduced to about half of control levels, while control peptides were without effect. Cadherin-blockade did not prevent maturation of OPs, since oligodendrocytes showing myelin basic protein immunostaining were still found in these cultures. However, many of the cell processes did not colocalize with calbindin-positive axons. From these data we conclude that N-cadherin is important for the initial contact between a myelinating oligodendrocyte and axons and significantly contributes to the success of myelination.

Animals↗
PubMed2000

Gradients of ephrin-A2 and ephrin-A5b mRNA during retinotopic regeneration of the optic projection in adult zebrafish.

Regeneration of optic axons in the continuously growing optic system of adult zebrafish was analyzed by anterograde tracing and correlated with the mRNA expression patterns of the recognition molecules ephrin-A2 and ephrin-A5b in retinal targets. The optic tectum and diencephalic targets are all reinnervated after a lesion. However, the rate of erroneous pathway choices was increased at the chiasm and the bifurcation between the ventral and dorsal brachium of the optic tract compared to unlesioned animals. Tracer application to different retinal positions revealed retinotopic reinnervation of the tectum within 4 weeks after the lesion. In situ hybridization analysis indicated the presence of rostral-low to caudal-high gradients of ephrin-A2 and ephrin-A5b mRNAs in unlesioned control tecta and after a unilateral optic nerve lesion. By contrast, the parvocellular superficial pretectal nucleus showed retinotopic organization of optic fibers but no detectable expression of ephrin-A2 and ephrin-A5b mRNAs. However, a row of cells delineating the terminal field of optic fibers in the dorsal part of the periventricular pretectal nucleus was intensely labeled for ephrin-A5b mRNA and may thus provide a stop signal for ingrowing axons. Ephrin-A2 and ephrin-A5b mRNAs were not detectable in the adult retina, despite their prominent expression during development. Thus, given a complementary receptor system in retinal ganglion cells, expression of ephrin-A2 and ephrin-A5b in primary targets of optic fibers in adult zebrafish may contribute to guidance of optic axons that are continuously added to the adult projection and of regenerating axons after optic nerve lesion.

Age Factors↗
PubMed2000

Tenascin-R inhibits regrowth of optic fibers in vitro and persists in the optic nerve of mice after injury.

Tenascin-R, an extracellular matrix constituent expressed by oligodendrocytes and some neuronal cell types, may contribute to the inhibition of axonal regeneration in the adult central nervous system. Here we show that outgrowth of embryonic and adult retinal ganglion cell axons from mouse retinal explants is significantly reduced on homogeneous substrates of tenascin-R or a bacterially expressed tenascin-R fragment comprising the epidermal growth factor-like repeats (EGF-L). When both molecules are presented as a sharp substrate border, regrowing adult axons do not cross into the tenascin-R or EGF-L containing territory. All in vitro experiments were done in the presence of laminin, which strongly promotes growth of embryonic and adult retinal axons, suggesting that tenascin-R and EGF-L actively inhibit axonal growth. Contrary to the disappearance of tenascin-R from the regenerating optic nerve of salamanders (Becker et al., J Neurosci 19:813-827, 1999), the molecule remains present in the lesioned optic nerve of adult mice at levels similar to those in unlesioned control nerves for at least 63 days post-lesion (the latest time point investigated), as shown by immunoblot analysis and immunohistochemistry. In situ hybridization analysis revealed an increase in the number of cells expressing tenascin-R mRNA in the lesioned nerve. We conclude that, regardless of the developmental stage, growth of retinal ganglion cell axons is inhibited by tenascin-R and we suggest that the continued expression of the protein after an optic nerve crush may contribute to the failure of adult retinal ganglion cells to regenerate their axons in vivo.

Animals↗
PubMed2000

Increased spontaneous unit activity and appearance of spontaneous negative potentials in the goldfish tectum during refinement of the optic projection.

Spontaneous (not retinally driven) postsynaptic activity was examined during activity-dependent refinement of optic fibers in the goldfish tectum. Unit recordings in vivo and in vitro demonstrated that spontaneous tectal activity increased to 150% of normal during refinement at 1-2 months after optic nerve crush and subsequently returned to baseline over the next month. This increase was not mimicked by long-term denervation indicating an effect specifically influenced by regenerating fibers. Loss of optic input was also found to induce spontaneous negative potentials (SNPs) rapidly in the tectum. SNPs were negative, monophasic potentials of 70-120 msec duration and -0.15 to -1.5 mV amplitude. SNPs occurred with no apparent periodicity at a frequency of approximately 0.3-0.6 Hz. Multiple electrode recordings and depth analysis showed that SNPs were localized events occurring in columnar domains of tectum a few hundred micrometers wide. Cross-correlation analysis revealed that SNPs were strongly correlated with local unit bursting, suggesting SNPs are generated by the summed synaptic and spike currents of coactive cells in small regions of the tectum. SNPs were suppressed by a low concentration of APV indicating they were regulated by NMDA receptors. During regeneration, the number and size of SNPs reached a peak during refinement and subsequently decreased, eventually disappearing. This temporal association with refinement suggests that these patterns of postsynaptic activity may have functional relevance. It is hypothesized that SNPs or the underlying activity that produces them increases the excitability of target cells, allowing the weak, less-convergent input from regenerating axons to drive target groups of cells in the tectum during refinement.

2-Amino-5-phosphonovalerate↗
PubMed2000

Alpha1-antitrypsin deficiency and inflammatory bowel diseases.

OBJECTIVE: To evaluate a possible etiologic role of alpha1-antitrypsin deficiency (alpha1AD), most frequently caused by a Z allele mutation, in ulcerative colitis (UC) and Crohn disease (CD). PATIENTS AND METHODS: This retrospective study included 10 patients diagnosed with and/or treated for inflammatory bowel disease (IBD) between 1976 and 1997 and identified from the Mayo Clinic Medical Index System. All 10 patients had either alpha1AD and CD or alpha1AD and UC. The alpha1-antitrypsin (alpha1AT) types and levels were determined with isoelectric focusing testing. The allele types, representing genotypes, were designated PiZZ (or ZZ) for homozygotes and PiMZ (or MZ) for heterozygotes. RESULTS: Seven patients had UC: 4 were genotype ZZ and 3 MZ. Four of these 7 patients had emphysema, 2 had asthma, and 1 had chronic bronchitis. Five were cigarette smokers, but only 1 had smoked coincident with activity of her UC. Two of the UC patients never smoked, and 1 of these 2 had asthma. Three of the 10 patients had CD, 2 genotype ZZ and 1 MZ. Two of the 3 patients were long-term cigarette smokers, and both had emphysema. Nine of the 10 patients with UC and alpha1AD required surgery. CONCLUSIONS: The need for surgery in patients with UC and alpha1-AD may point to a unique phenotypic subgroup of patients with alpha1AD and severe UC. Further studies are required to substantiate the etiologic role of alpha1AD in IBD. Our observations, if confirmed by future studies, suggest that in patients with both IBD and chronic obstructive pulmonary disease, alpha1AD testing should be considered.

Adult↗
PubMed1999

Large-scale synaptic errors during map formation by regeneration optic axons in the goldfish.

During the formation of visual maps, growing axons initially form a map by using topographically distributed cues that direct their growth and branching to the appropriate target region. This initial map is typically roughly retinotopic and is subsequently refined through activity-dependent rearrangement or cell death. Although synaptic connections are thought to be rearranged during the later refinement phase, there is no clear evidence that synapses are being formed during the initial targeting phase of development. Also, because optic fiber growth can be accurately directed during normal development, it is unclear whether regenerative fibers that have more pathway disorder would behave similarly. This issue was addressed by using optic fibers of goldfish that have the capacity to regenerate a retinotopic projection and can reestablish a rough retinotopic order without impulse activity. The optic nerve of goldfish was crushed, and at various times later, a small number of optic fibers in ventronasal retina was labeled with wheatgerm agglutinin-horseradish peroxidase. The tectum was then processed for electron microscopy to look at the distribution of labeled synapses during regeneration. At 3 weeks, synapses were observed at the far anterior end of the tectum and none were yet seen at the correct posterior retinotopic position. At 4-5 weeks, synapses were seen in nearly equal numbers at the incorrect anterior end and at both correct (retinotopic) and incorrect posterior positions. At late stages of regeneration, synapses were restricted to their correct posterior retinotopic position in the tectum, as they were in normal fish. These findings show that the formation of global retinotopic order entails the formation and subsequent elimination of a large number of highly ectopic synapses. Synaptic rearrangement is a major feature of targeting in this system and may be required for the regeneration of a retinotopic projection.

Animals↗
PubMed1999

Activity-dependent refinement in the goldfish retinotectal system is mediated by the dynamic regulation of processes withdrawal: an in vivo imaging study.

Imaging of regenerating optic fibers in living adult goldfish was used to visualize arbor restructuring during activity-dependent refinement. A small number of neighboring retinal ganglion cells were labeled with DiI and observed in the tectum of the living animal for 5-7 hours during the period of activity-dependent refinement. In contrast to earlier stages of regeneration, many optic arbors were surprisingly stable, showing little or no change. The observed changes were mainly retractions, and these were affected by retinotopic position and activity. Axon branches in retinotopic positions changed by much smaller amounts than ectopic axons, but in fish with retinal tetrodotoxin impulse blockade, no systematic difference was observed as a function of tectal position. Otherwise, impulse blockade had no notable effects.

Animals↗
PubMed1999

Tenascin-R inhibits the growth of optic fibers in vitro but is rapidly eliminated during nerve regeneration in the salamander Pleurodeles waltl.

Tenascin-R is a multidomain molecule of the extracellular matrix in the CNS with neurite outgrowth inhibitory functions. Despite the fact that in amphibians spontaneous axonal regeneration of the optic nerve occurs, we show here that the molecule appears concomitantly with myelination during metamorphosis and is present in the adult optic nerve of the salamander Pleurodeles waltl by immunoblots and immunohistochemistry. In vitro, adult retinal ganglion cell axons were not able to grow from retinal explants on a tenascin-R substrate or to cross a sharp substrate border of tenascin-R in the presence of laminin, indicating that tenascin-R inhibits regrowth of retinal ganglion cell axons. After an optic nerve crush, immunoreactivity for tenascin-R was reduced to undetectable levels within 8 d. Immunoreactivity for the myelin-associated glycoprotein (MAG) was also diminished by that time. Myelin was removed by phagocytosing cells at 8-14 d after the lesion, as demonstrated by electron microscopy. Tenascin-R immunoreactivity was again detectable at 6 months after the lesion, correlated with remyelination as indicated by MAG immunohistochemistry. Regenerating axons began to repopulate the distal lesioned nerve at 9 d after a crush and grew in close contact with putative astrocytic processes in the periphery of the nerve, close to the pia, as demonstrated by anterograde tracing. Thus, the onset of axonal regrowth over the lesion site was correlated with the removal of inhibitory molecules in the optic nerve, which may be necessary for successful axonal regeneration in the CNS of amphibians.

Animals↗
PubMed1999

Expression of polysialylated NCAM but not L1 or N-cadherin by regenerating adult mouse optic fibers in vitro.

This study asks if there might be irreversible maturational changes in adult neurons that limit their capacity to regenerate. Retina from adult and embryonic mouse were placed in culture on laminin substrates so that regenerating adult optic fibers could be compared to growing embryonic fibers. Several cell adhesion molecules (CAMs) known to mediate the growth of embryonic neurites on astrocytes were assayed by immunocytochemistry: L1, N-cadherin, and NCAM. Thy 1.2, a potential CAM with inhibitory activity, was also examined. As in vivo, embryonic fibers were found to express both L1 and N-cadherin. In contrast, regenerating adult fibers had no detectable amounts of either of these CAMs. N-Cadherin is normally down regulated during development so its absence in adult fibers suggests it can not be reexpressed during regeneration. L1 is normally found in the proximal regions of adult optic fibers so its absence indicates it is not expressed or transported in regenerating fibers. Adult regenerating fibers expressed high levels of Thy 1.2, which was undetectable in embryonic optic fibers. Thy 1.2 is normally found in mature fibers, indicating this phenotypic feature is preserved during regeneration. Both adult and embryonic fibers showed strong reactivity for NCAM, which in vivo is normally found in embryonic and at lower levels in adult fibers. Surprisingly, both embryonic and regenerating adult fibers expressed high levels of polysialic acid, which is normally absent in adult fibers. NCAM may be one of few CAMs available to adult optic fibers for regeneration on astrocytes.

Animals↗
PubMed1998

Roger Sperry and his chemoaffinity hypothesis.

In the early 1940s, Roger Sperry performed a series of insightful experiments on the visual system of lower vertebrates that led him to draw two important conclusions: When optic fibers were severed, the regenerating fibers grew back to their original loci in the midbrain tectum to re-establish a topographical set of connections; and the re-establishment of these orderly connections underlay the orderly behavior of the animal. From these conclusions, he inferred that each optic fiber and each tectal neuron possessed cytochemical labels that uniquely denoted their neuronal type and position and that optic fibers could utilize these labels to selectively navigate to their matching target cell. This inference was subsequently formulated into a general explanation of how neurons form ordered interconnections during development and became known as the chemoaffinity hypothesis. The origins of this hypothesis, the controversies that surrounded it for several decades and its eventual acceptance, are discussed in this article.

Animals↗
PubMed1998

Colonic histopathology in untreated celiac sprue or refractory sprue: is it lymphocytic colitis or colonic lymphocytosis?

Colonic histopathology in some patients with untreated celiac sprue and refractory sprue has been said to be indistinguishable from lymphocytic colitis, but there have been no objective comparisons on which this is based. The purpose of this study was to determine the prevalence and to characterize the nature of colonic histopathology at the time of diagnosis in patients with celiac or refractory sprue. Colonoscopic biopsy specimens obtained at the time of diagnosis from 16 patients with celiac sprue, six patients with refractory sprue, nine patients with lymphocytic colitis, and five normal controls were analyzed blindly by histological and morphometric methods, quantitating the number and specific subtypes of inflammatory cells within the lamina propria and epithelium. Immunoperoxidase staining of intraepithelial lymphocytes with a monoclonal antibody to CD8 also was performed. Three of 16 patients with untreated celiac sprue (19%) were thought to have colonic histological abnormalities, which by morphometry consisted of slightly increased numbers of lymphocytes in the surface epithelium and lamina propria, many of which were CD8-positive. These abnormalities were distinguishable from lymphocytic colitis by the lack of increased overall lamina propria cellularity and surface epithelial abnormalities, and by fewer intraepithelial lymphocytes. In refractory sprue, colonic histological abnormalities were more frequent than in celiac sprue, occurring in four of six patients (67%), more pronounced, and identical to those in the lymphocytic colitis syndrome. However, colonic intraepithelial lymphocytes in lymphocytic colitis were mostly CD8-positive, whereas those in the colitis of refractory sprue rarely were. Mild colonic lymphocytosis in patients with untreated celiac sprue should be distinguished from lymphocytic colitis by the lack of surface epithelial abnormalities, the lack of increased cellularity of the lamina propria, and the lack of ongoing watery diarrhea after treatment with a gluten-free diet. In contrast, colonic histopathology in refractory sprue is indistinguishable from lymphocytic colitis, although immunohistochemical differences do exist.

Adolescent↗
PubMed1998

Effects of passive immunization using antibody against an alpha-inhibin peptide on follicle-stimulating hormone concentrations and litter size in sows.

The objective of the experiment was to determine whether passive immunization against inhibin at weaning would increase FSH secretion and thereby influence postweaning reproductive performance in sows. Commercial Yorkshire sows (n = 173) were assigned within parity to 5 alpha-inhibin fragment antibody (alpha-IF-Ab) dosage groups: 0 (control), 3.25, 6.5, 13 and 26 RP-2 kU/kg alpha-IF-Ab. Antibody had been semipurified from ovine antisera raised against alpha-IF, a peptide that mimicked the N-terminal region of inhibin's alpha-subunit. A RP-2 U refers to a laboratory reference preparation. Sows were administered a single intramuscular injection of control solution or alpha-IF-Ab just before 21-d-old piglets were weaned. Blood samples were taken immediately before immunization and 24 h later. Sows were bred upon expression of estrus. Serum alpha-IF-Ab titers in sows 24 h following passive immunization increased (P < 0.001) with dosage. In control sows serum FSH concentrations decreased 24% by 24 h postweaning (P < 0.001). The decrease was diminished or prevented by alpha-IF-Ab treatment in a dose-responsive manner (P < 0.001). Most (167/173) sows were bred within 10 d postweaning, and wean-to-service intervals tended (P < 0.1) to be shorter in the 13 and 26 RP-2 kU/kg alpha-IF-Ab dosage groups. Farrowing rate was 72% (124/173) and was similar among sows in the alpha-IF-Ab dosage groups. Litter size, expressed as total or live piglets born per sow or per sow farrowed, was unchanged by alpha-IF-Ab treatment. Results demonstrate that 1) inhibin plays a key role in regulating FSH secretion at weaning, and 2) blocking the acute postweaning drop in FSH secretion has little if any effect on subsequent reproductive performance.

Animals↗
PubMed1997

The neurite-promoting effect of laminin is mediated by different mechanisms in embryonic and adult regenerating mouse optic axons in vitro.

Retinal explants from embryonic or adult mice were placed on laminin or merosin substrates and the outgrowth of optic fibers was assayed under serum-free conditions. Both substrates strongly promoted outgrowth. A blocking antibody to the beta1/beta3 integrin subunits completely blocked laminin-dependent growth of embryonic optic fibers but had no detectable effect on adult fibers. Similarly, a blocking antibody against the main neurite-promoting region within the globular domain of the E8 fragment of laminin inhibited growth of embryonic fibers but had no effect on adult optic fibers. The beta1 integrin subunit was identified immunohistochemically on both embryonic and adult fibers. These findings indicate that adult fibers have lost the beta1 function which dominates laminin-dependent growth in embryonic fibers but express a receptor for laminin-dependent growth that is not detectable in embryonic fibers. These findings suggest that there are intrinsic differences between embryonic and adult optic fibers that may have implications for regenerative failure in the central nervous system of adult mammals .

Age Factors↗