PubMed Health⌕ Search

Biomedical subjects

S Meyers

Publications and source records attributed to S Meyers.

At least 19 recordsLinked to original sources
PubMed2001

Sensate radial forearm free flaps in tongue reconstruction.

BACKGROUND: Successful rehabilitation after ablative surgery requires not only the reconstruction of 3-dimensional form but also the restoration of physiologic function. OBJECTIVE: To assess sensory recovery of reinnervated radial forearm flaps used for tongue reconstruction. PATIENTS AND METHODS: Seventeen patients, who underwent reconstruction of glossectomy defects with reinnervated radial forearm free flaps, formed the study group. Recovery of sensation was measured by both subjective and detailed objective tests 8 months after surgery. Sensory function of the flap was compared with that of the normal residual tongue or the adjacent oral mucosa and the contralateral forearm donor site. RESULTS: All patients involved in this study had tongue defects of hemiglossectomy or greater and adjacent floor of the mouth. Sensory recovery was observed in all of the 17 patients within 8 months. Detailed sensory testing showed that median static 2-point discrimination, moving 2-point discrimination, and pressure sensitivity (1.2 cm, 0.8 cm, and 3.7 psi, respectively) were subjectively greater in the innervated forearm flaps than in the contralateral forearm donor site (2.3 cm, 1.7 cm, and 4.6 psi, respectively) (P= .064) and similar to those of the normal tongue (0.9 cm, 0.5 cm, and 3.6 psi). CONCLUSIONS: In all modalities examined, sensate free flaps proved superior in sensory fidelity to the native forearm donor site and closely approached that of the normal tongue. Microsurgical reinnervation of flaps should be considered in tongue reconstruction.

Adult↗
PubMed2001

Fine-mapping and construction of a bovine contig spanning the ovine callipyge locus.

The callipyge (CLPG) gene was fine-mapped by linkage analysis to a 4.6-cM chromosome interval on distal ovine OAR18q, flanked by microsatellite markers IDVGA30 and OY3. The OAR18q linkage map and human HSA14q transcript map were aligned by genotyping two bovine-hamster whole-genome radiation hybrid panels with the microsatellite markers, as well as with sequences corresponding to HSA 14q genes. Using Type I loci mapping to the IDVGA30-OY3 interval as anchor points, we have constructed a 1.4-Mb bovine BAC contig containing the IDVGA30-OY3 interval. We demonstrate that the IDVGA30-OY3 interval spans approximately 770 kb and contains at least four genes: YY1, WARS, DLK1, and GTL2.

Animals↗
PubMed2001

Detection of tumorigenesis in rat bladders with optical coherence tomography.

Optical coherence tomography (OCT) is a novel technique that enables noninvasive cross-sectional imaging of biological tissues. Because of its high resolution (approximately 10 microm), superior dynamic range (140 dB in our case) and up to 2-3 mm penetration depth, OCT is potentially useful for noninvasive screening of superficial lesions. Bladder cancer arises within the transitional epithelium. Despite the ability to visualize the epithelium via cystoscopy, it is often difficult to detect early epithelial cancers and to determine their penetration to the underlying layers. To investigate the potential of OCT to enhance imaging of bladder cancers and other epithelial lesions, we applied OCT to normal and diseased bladder epithelium, and correlated the results with histological findings. OCT images of porcine bladder (a close homolog of human bladder) confirm the ability of this method to image human tissues. To determine whether OCT can track the course of bladder cancer, a standard rat model of bladder cancer in which Fisher rats are exposed to methyl-nitroso-urea (MNU), was followed both with OCT and histological studies. Our results show that the micro morphology of porcine bladder such as the urothelium, submucosa and muscles is identified by OCT and well correlated with the histological evaluations. OCT detected edema, inflammatory infiltrates, and submucosal blood congestion as well as the abnormal growth of urothelium (e.g., papillary hyperplasia and carcinomas). By contrast, surface imaging, which resembles cystoscopy, provided far less sensitivity and resolution than OCT. This is the first OCT study of any tumor documented in a systematic fashion, and the results suggest the potential of OCT for the noninvasive diagnosis of both bladder inflammatory lesions and early urothelial abnormalities, which conventional cystoscopy often misses, by imaging characterization of the increases in urothelial thickening and backscattering. However, because of the depth limitation, OCT may have limited applications in staging the invasion of higher-state urothelial cancers, especially for papillary carcinomas.

Animals↗
PubMed2001

Type B leukemogenic virus has a T-cell-specific enhancer that binds AML-1.

Type B leukemogenic virus (TBLV) induces rapidly appearing T-cell tumors in mice. TBLV is highly related to mouse mammary tumor virus (MMTV) except that TBLV long terminal repeats (LTRs) have a deletion of negative regulatory elements and a triplication of sequences flanking the deletion. To determine if the LTR triplication represents a viral enhancer element, we inserted the triplication upstream and downstream in either orientation relative to the thymidine kinase promoter linked to the luciferase gene. These experiments showed that upregulation of reporter gene activity by the TBLV triplication was relatively orientation independent, consistent with the activity of eukaryotic enhancer elements. TBLV enhancer activity was observed in T-cell lines but not in fibroblasts, B cells, or mammary cells, suggesting that enhancer function is cell type dependent. To analyze the transcription factor binding sites that are important for TBLV enhancer function, we prepared substitution mutations in a reconstituted C3H MMTV LTR that recapitulates the deletion observed in the TBLV LTR. Transient transfections showed that a single mutation (556M) decreased TBLV enhancer activity at least 20-fold in two different T-cell lines. This mutation greatly diminished AML-1 (recently renamed RUNX1) binding in gel shift assays with a mutant oligonucleotide, whereas AML-1 binding to a wild-type TBLV oligomer was specific, as judged by competition and supershift experiments. The 556 mutation also reduced TBLV enhancer binding of two other protein complexes, called NF-A and NF-B, that did not appear to be related to c-Myb or Ets. AML-1 overexpression in a mammary cell line enhanced expression from the TBLV LTR approximately 30-fold. These data suggest that binding of AML-1 to the TBLV enhancer, likely in combination with other factors, is necessary for optimal enhancer function.

Animals↗
PubMed2001

ETO, a target of t(8;21) in acute leukemia, makes distinct contacts with multiple histone deacetylases and binds mSin3A through its oligomerization domain.

t(8;21) and t(16;21) create two fusion proteins, AML-1-ETO and AML-1-MTG16, respectively, which fuse the AML-1 DNA binding domain to putative transcriptional corepressors, ETO and MTG16. Here, we show that distinct domains of ETO contact the mSin3A and N-CoR corepressors and define two binding sites within ETO for each of these corepressors. In addition, of eight histone deacetylases (HDACs) tested, only the class I HDACs HDAC-1, HDAC-2, and HDAC-3 bind ETO. However, these HDACs bind ETO through different domains. We also show that the murine homologue of MTG16, ETO-2, is also a transcriptional corepressor that works through a similar but distinct mechanism. Like ETO, ETO-2 interacts with N-CoR, but ETO-2 fails to bind mSin3A. Furthermore, ETO-2 binds HDAC-1, HDAC-2, and HDAC-3 but also interacts with HDAC-6 and HDAC-8. In addition, we show that expression of AML-1-ETO causes disruption of the cell cycle in the G(1) phase. Disruption of the cell cycle required the ability of AML-1-ETO to repress transcription because a mutant of AML-1-ETO, Delta469, which removes the majority of the corepressor binding sites, had no phenotype. Moreover, treatment of AML-1-ETO-expressing cells with trichostatin A, an HDAC inhibitor, restored cell cycle control. Thus, AML-1-ETO makes distinct contacts with multiple HDACs and an HDAC inhibitor biologically inactivates this fusion protein.

Amino Acid Sequence↗
PubMed2001

Use of dermal grafts in reconstructing deep nasal defects and shaping the ala nasi.

BACKGROUND: Deep postsurgical defects on the nose and alar rim pose a challenge to repair. Several techniques are available to reestablish normal contour. If a depressed area is anticipated, dermal grafts can be used to fill the defect and soften contour irregularities. The technique is simple and can prevent the need for a more complicated repair. OBJECTIVE: To reestablish normal contour over nasal defects by using dermal grafts as a tissue filler in conjunction with graft and flap reconstruction. METHODS: Fifteen patients had contour deformities that could be improved with dermal graft insertion under their full-thickness skin grafts or flaps. Fourteen of these patients had nasal defects and one had a vermilion border defect that resulted from tumor removal by Mohs surgery. Patient selection, dermal graft harvesting, and surgical technique are described. RESULTS: All patients showed cosmetic benefit from dermal grafting. Contour was improved in each case. Fourteen patients had no significant complications. One flap showed tip necrosis in a patient who was a smoker. No resorption of the dermal grafts occurred over the 1- to 9-month follow-up period. No cyst formation occurred. CONCLUSION: Dermal grafts can be used during the initial repair of postsurgical nasal defects. These dermis grafts effectively fill the defect and restore contour. The technique is simple, easily mastered, and can obviate the need for more complicated repair.

Aged↗
PubMed2000

Nuclear import and subnuclear localization of the proto-oncoprotein ETO (MTG8).

ETO (MTG8) was first described due to its involvement in the (8;21) translocation frequently observed in acute myeloid leukemias. In the t(8;21) the AML1 gene on chromosome 21 is fused to ETO on chromosome 8. The resultant hybrid protein is comprised of the DNA binding domain of AML-1 and the majority of ETO. This study examines the subnuclear distributions of ETO, AML-1B and AML-1/ETO proteins fused to green fluorescence protein in living cells using fluorescence microscopy. Further, we identified a 40 amino acid portion of ETO (amino acids 241-280) that was sufficient to cause nuclear import of green fluorescent protein. Mutational analysis demonstrated that lysine 265 and/or arginine 266 were required for nuclear import of ETO, but that the surrounding basic residues were not critical. ETO interacted with the nuclear import proteins importin-alpha and beta in vitro, and mutations in ETO that abolish nuclear localization also abolished the in vitro interaction with importin-alpha and beta. These data suggest that ETO enters the nucleus via an importin-mediated pathway. Additionally, ETO and AML-1/ETO co-localized to punctate nuclear bodies distinct from those containing promyelocytic leukemia protein. Nuclear body formation was dependent upon a region of ETO N-terminal to the nuclear localization signal. Thus, ETO and AML-1/ETO reside in potentially novel subnuclear compartments.

Amino Acid Sequence↗
PubMed2000

Alterations in subnuclear trafficking of nuclear regulatory factors in acute leukemia.

The nuclear matrix plays an important role in the functional organization of the nucleus in part by locally concentrating regulatory factors involved in nucleic acid metabolism. A number of nuclear regulatory proteins initially identified due to their involvement in human cancer are localized to discrete nuclear matrix-attached foci and correct nuclear partitioning likely plays a role in their function. Two such examples are promyelocytic leukemia (PML) and acute myelogenous leukemia-1 (AML-1; Runx1). PML, the target of the t(15;17) in acute PML, is localized to PML nuclear bodies (also termed Nuclear Domain 10 and PML oncogenic domains), a nuclear matrix-associated body whose function appears to be quite complex, with probable roles in cancer, apoptosis, and in acute viral infections. In t(15;17)-containing leukemic cells, the PML nuclear bodies are disrupted, but reform when the leukemic cells are induced to differentiate in the presence of all-trans retinoic acid. AML1 (RUNX1) is a key regulator of hematopoietic differentiation and AML1 proteins are found in nuclear compartments that reflect their roles in transcriptional activation and repression. The t(8;21), associated with AML, results in a chimeric transcription factor, AML-1/ETO (eight twenty one), that remains attached to the nuclear matrix through targeting signals contained in the ETO protein. When co-expressed, ETO and AML-1/ETO co-localize to a nuclear compartment distinct from that of AML1 or PML nuclear bodies. Interestingly, enforced expression of ETO or AML-1/ETO changes the average number of PML nuclear bodies per cell. Thus, chromosomal translocations involving AML1 result in altered nuclear trafficking of the transcription factor as well as other changes to the nuclear architecture. J. Cell. Biochem. Suppl. 35:93-98, 2000.

Animals↗
PubMed2000

Changes in cerebral blood flow and distribution associated with acute increases in plasma sodium and osmolality of chronic hyponatremic rats.

The cause of the osmotic demyelination syndrome that follows too rapid correction of chronic hyponatremia (CHN) is unknown. Recently, we reported in CHN rats an association between blood-brain barrier (BBB) disruption occurring as early as 3 h into correction and subsequent demyelination. Given the changes in brain water and blood volume which occur during correction of CHN, we hypothesized that the same correction protocol that causes demyelination might alter cerebral blood flow (CBF) during correction, thereby possibly contributing to BBB disruption and demyelination. Ten CHN rats were given hypertonic sodium intraperitoneally and its effect on CBF was continuously monitored for 3 h by magnetic resonance flow imaging. Over the subsequent 3 h, plasma sodium rose from 110.8 to 127.6 mEq/liter (P < 0.001) but neither mean arterial blood pressure nor arterial CO(2) tension changed significantly. By 30 min, CBF increased by 50% in cortical and subcortical areas (P < 0.001) and remained elevated for the next 60 min. After 2 h, cortical flow was no longer elevated significantly and by 3 h it had returned to control values. Subcortical flow, however, significantly exceeded control values throughout the 3 h so that after 2 h the ratio of cortical to subcortical blood flow had fallen from 1.17 to 0.91 (P < 0.05). Although the mechanism by which increased plasma sodium and osmolality alters CBF is uncertain, the results suggest that changes in CBF may be part of a cascade of cerebrovascular disturbances including endothelial or parenchymal damage, mechanical events, metabolic disturbances, or cytokine release which eventually lead to BBB disruption and subsequent demyelination.

Animals↗
PubMed2000

Construction and characterization of an ovine BAC contig spanning the callipyge locus.

We describe the construction of an ovine BAC contig spanning a 4.6 centimorgan (cM) chromosome segment known to contain the callipyge (CLPG) locus. The contig comprises 21 ovine BAC clones jointly covering approximately 900 kilobases (Kb). Two gaps in the BAC contig, spanning 10 and 7.5 Kb, respectively, were bridged by long range PCR. The corresponding chromosome region was shown to be characterized by an unusually low Kb to cM ratio (164 Kb/cM) and a high density of Not1 sites (1:126 Kb) possibly reflecting a high gene density in the corresponding chromosome region. Equivalent amplification of 64 sequence tagged sites spanning the corresponding region from homozygous +/+ and CLPG/CLPG individuals disproves the hypothesis of a major deletion causing the CLPG mutation.

Animals↗
PubMed2000

Use of neurotransmitter precursors for treatment of depression.

Insufficient activity of the neurotransmitters serotonin and norepinephrine is a central element of the model of depression most widely held by neurobiologists today. In the late 1970s and 1980s, numerous studies were performed in which depressed patients were treated with the serotonin precursors L-tryptophan and 5-hydroxytryptophan (5-HTP), and the dopamine and norepinephrine precursors tyrosine and L-phenylalanine. This article briefly reviews the published research on the efficacy of neurotransmitter precursors in treating depression, highlights the findings of studies, and discusses issues regarding the interpretation of those findings. The nature of the studies makes it difficult to draw firm conclusions regarding the efficacy of neurotransmitter precursors for treating depression. While there is evidence that precursor loading may be of therapeutic value, particularly for the serotonin precursors 5-HTP and tryptophan, more studies of suitable design and size might lead to more conclusive results. However, the evidence suggests neurotransmitter precursors can be helpful in patients with mild or moderate depression.

5-Hydroxytryptophan↗
PubMed1999

ETO-2, a new member of the ETO-family of nuclear proteins.

The t(8;21) is associated with 12-15% of acute myelogenous leukemias of the M2 subtype. The translocation results in the fusion of two genes, AML1 (CBFA2) on chromosome 21 and ETO (MTG8) on chromosome 8. AML1 encodes a DNA binding factor; the ETO protein product is less well characterized, but is thought to be a transcription factor. Here we describe the isolation and characterization of ETO-2, a murine cDNA that encodes a new member of the ETO family of proteins. ETO-2 is 75% identical to murine ETO and shares very high sequence identities over four regions of the protein with ETO (domain I-III and zinc-finger). Northern analysis identifies ETO-2 transcripts in many of the murine tissues analysed and in the developing mouse embryo. ETO-2 is also expressed in myeloid and erythroid cell lines. We confirmed the nuclear localization of ETO-2 and demonstrated that domain III and the zinc-finger region are not required for nuclear localization. We further showed that a region within ETO, containing domain II, mediates dimerization among family members. This region is conserved in the oncoprotein AML-1/ETO. The recent identification of another ETO-like protein, myeloid translocation gene-related protein 1, together with the data presented here, demonstrates that at least three ETO proteins exist with the potential to form dimers in the cell nucleus.

Amino Acid Sequence↗
PubMed1999

Ovarian cancer: comparison of observer performance for four methods of interpreting CT scans.

PURPOSE: To assess the effects of four interpretative methods on observers' mean sensitivity and specificity by using computed tomography (CT) of ovarian carcinoma as a model. MATERIALS AND METHODS: CT scans in 98 patients with ovarian carcinoma and 49 women who were disease free were retrospectively reviewed by four experienced blinded radiologists to compare single-observer reading, single-observer reading with an anatomic checklist, paired-observer reading (simultaneous double reading), and replicated reading (combination of two independent readings). Confidence level scoring was used to identify three possible disease forms in each patient: extranodal tumor, lymphadenopathy, and ascites. Patient conditions were then categorized as abnormal or normal. RESULTS: There were no significant improvements in sensitivity or specificity for classification of patient conditions as abnormal or normal when comparing single-observer interpretation with single-observer interpretation with a checklist or paired-observer interpretation. Although there was no significant improvement in the mean sensitivity (93% vs 94%) by using the replicated reading method, there was a statistically significant improvement in mean specificity (85% vs 79%) for the replicated readings compared with single-observer interpretations (P < .05). CONCLUSION: Diagnostic aids such as checklists and paired simultaneous readings did not lead to an improved mean observer performance for experienced readers. However, an increase in the mean specificity occurred with replicated readings.

Female↗