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T Neuman

Publications and source records attributed to T Neuman.

At least 19 recordsLinked to original sources
PubMed2001

Cell-type-specific expression of the TFIID component TAF(II)135 in the nervous system.

A number of nervous system-specific enhancers and silencers have been isolated and characterized. However, the detailed mechanism of cell- and tissue-specific regulation of transcription is to a large extent unknown and the role of the basal transcriptional complex components in these processes is mostly unclear. Here we demonstrate that mRNA levels of TATA binding protein-associated factor TAF(II)135 are upregulated in neuronal cells during development. In addition, induction of neuronal differentiation of teratocarcinoma PCC7 cells results in dramatic induction of TAF(II)135 mRNA levels and activation of a variety of promoters. The stimulation of promoter activity in differentiating cells is mimicked by the overexpression of TAF(II)135. As neuronal differentiation requires changes in the general pattern of transcriptional activity, we suggest that increased levels of TAF(II)135 facilitate the induction of a large number of neuronal genes.

Animals↗
PubMed2001

Regulation of c-met expression in rats with acute hepatic failure.

BACKGROUND: Earlier we described a model of fulminant hepatic failure (FHF) in the rat where partial hepatectomy is combined with induction of right liver lobe necrosis. In FHF rats, lack of hepatocyte proliferation was associated with delayed expression of HGF and HGF receptor c-met. Since the c-met promoter region has Sp1 binding sites, we decided to examine whether in FHF rats down-regulation of c-met is associated with decreased Sp1 function and whether changes in blood HGF, IL-6, and TGFbeta1 levels might be responsible for these effects. MATERIALS AND METHODS: Induction of FHF, partial (2/3) hepatectomy (PH), and sham hepatectomy (SH) was performed in adult Sprague-Dawley rats. The levels of c-met mRNA and Sp1 DNA binding activity were studied in rat liver remnants at different time points after surgery. Blood levels of HGF, IL-6, and TGFbeta1 were also measured in these rats. Additionally, the effects of treatment with TGF-beta1, IL-6, or a combination of both on c-met expression and Sp1 DNA binding were studied in HGF-induced rat hepatocyte cultures. RESULTS: Compared to SH rats, in PH rat livers c-met was up-regulated after 6 h and Sp1 DNA binding was at or only slightly lower than levels at all time points studied. In FHF rat livers, c-met expression was markedly reduced after 2 and 6 h, moderate after 12 h, and undetectable after 24 h. At the same time, Sp1 DNA binding was detected at 2 h postinduction only. In FHF rats, blood levels of all three cytokines showed early and sustained elevation. In vitro, IL-6 had no effect on c-met expression, whereas TGFbeta1 up-regulated c-met. When used alone, none of the cytokines affected Sp1 DNA binding activity. In contrast, a combination of IL-6 and TGFbeta1 down-regulated c-met expression as well as Sp1 DNA binding activity. These effects were dependent on the IL-6 concentration used. This study suggests that following massive loss of hepatocyte mass in rats, early increase in blood IL-6 and TGFbeta1 levels may weaken the expression of HGF receptor c-met in surviving hepatocytes through suppression of Sp1 DNA binding.

Animals↗
PubMed2000

Evolutionary conservation of the presumptive neural plate markers AmphiSox1/2/3 and AmphiNeurogenin in the invertebrate chordate amphioxus.

Amphioxus, as the closest living invertebrate relative of the vertebrates, can give insights into the evolutionary origin of the vertebrate body plan. Therefore, to investigate the evolution of genetic mechanisms for establishing and patterning the neuroectoderm, we cloned and determined the embryonic expression of two amphioxus transcription factors, AmphiSox1/2/3 and AmphiNeurogenin. These genes are the earliest known markers for presumptive neuroectoderm in amphioxus. By the early neurula stage, AmphiNeurogenin expression becomes restricted to two bilateral columns of segmentally arranged neural plate cells, which probably include precursors of motor neurons. This is the earliest indication of segmentation in the amphioxus nerve cord. Later, expression extends to dorsal cells in the nerve cord, which may include precursors of sensory neurons. By the midneurula, AmphiSox1/2/3 expression becomes limited to the dorsal part of the forming neural tube. These patterns resemble those of their vertebrate and Drosophila homologs. Taken together with the evolutionarily conserved expression of the dorsoventral patterning genes, BMP2/4 and chordin, in nonneural and neural ectoderm, respectively, of chordates and Drosophila, our results are consistent with the evolution of the chordate dorsal nerve cord and the insect ventral nerve cord from a longitudinal nerve cord in a common bilaterian ancestor. However, AmphiSox1/2/3 differs from its vertebrate homologs in not being expressed outside the CNS, suggesting that additional roles for this gene have evolved in connection with gene duplication in the vertebrate lineage. In contrast, expression in the midgut of AmphiNeurogenin together with the gene encoding the insulin-like peptide suggests that amphioxus may have homologs of vertebrate pancreatic islet cells, which express neurogenin3. In addition, AmphiNeurogenin, like its vertebrate and Drosophila homologs, is expressed in apparent precursors of epidermal chemosensory and possibly mechanosensory cells, suggesting a common origin for protostome and deuterostome epidermal sensory cells in the ancestral bilaterian.

Amino Acid Sequence↗
PubMed2000

Inhibition of signal transducer and activator transcription factor 3 in rats with acute hepatic failure.

In fulminant hepatic failure, survival is not possible without recovery of sufficient hepatocyte mass. Remarkably, only a few studies exist that provide insight into the mechanisms that control proliferation of residual hepatocytes after extensive hepatocyte loss. In this regard, the role of growth-regulatory factors, including pro-inflammatory cytokines such as interleukin-6 (IL-6), is not well understood. In the present study we show that in rats with critically low (10%) hepatocyte mass, whether with or without ongoing liver cell necrosis, inhibition of liver regeneration is associated with early and sustained increase in blood IL-6 levels. Under these conditions, the signal transducer and activator of transcription (Stat3) DNA binding activity was lowered at the time of G1/S cell-cycle transition. We further demonstrate that the protein inhibitor of activated Stat3 (PIAS3) and the suppressor of cytokine signaling (SOCS-1) were up-regulated early after induction of liver failure (6-12 h). In vitro, IL-6 induced PIAS3 expression in HGF stimulated rat hepatocytes. These findings suggest that after massive hepatocyte loss, an early and rapid rise in blood IL-6 levels may weaken the hepatic regenerative response through up-regulation of Stat3 inhibitors PIAS3 and SOCS-1.

Animals↗
PubMed2000

Fetal and adult human CNS stem cells have similar molecular characteristics and developmental potential.

The mammalian central nervous system (CNS) contains multipotent stem cells that develop into neurons, astrocytes and oligodendrocytes. Our current data show that fetal and adult human CNS stem cell isolates display similar proliferation kinetics, differentiate into three major cell types of the nervous system and express similar sets of regulatory genes. However, each individual CNS stem cell isolate could be distinguished by its specific gene expression and developmental potential.

Astrocytes↗
PubMed2000

Spirometry in normal subjects in sitting, prone, and supine positions.

OBJECTIVE: Determine whether pulmonary function testing is affected by patient positioning. METHODS: In a descriptive study with measurements made in a sequential but randomized order at a university-based pulmonary function laboratory, 20 healthy men, ages 18-50 years, were evaluated with spirometric assessment of forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and maximum voluntary ventilation (MVV) in the sitting, supine, and prone positions. Subjects were excluded for body mass index (BMI) > 30 kg/m2 or abnormal baseline spirometry. RESULTS: Comparing sitting to supine and prone positions, there was a statistically significant decline in the spirometry values (reported as percent of predicted normal +/- standard error of the mean). FVC was 102% +/- 4% while sitting, 95% +/- 4% while supine, and 94% +/- 4% while prone. FEV1 was 104% +/- 3% while sitting, 96% +/- 3% while supine, and 94% +/- 3% while prone. MVV was 115% +/- 4% while sitting, 102% +/- 4% while supine, and 97% +/- 3% prone. CONCLUSION: In healthy men with BMI < 30 kg/m2, changing from the sitting to supine or prone position results in statistically significant change in respiratory pattern. However, all spirometry values in each position were normal by American Thoracic Society definitions.

Adolescent↗
PubMed1999

Bioartificial liver treatment in rats with fulminant hepatic failure: effect on DNA-binding activity of liver-enriched and growth-associated transcription factors.

BACKGROUND: We earlier described a model of fulminant hepatic failure (FHF) in the rat where partial hepatectomy is combined with induction of right liver lobe necrosis. In FHF rats, lack of regeneration of the residual liver was associated with delayed expression of HGF and HGF receptor c-met and elevated blood HGF and TGF-beta1 levels. We then found that intrasplenic hepatocyte transplantation prolonged survival in FHF rats and triggered hepatocyte proliferation in the native liver. The latter effect was associated with accelerated expression of HGF and c-met mRNA in the liver and lowering of blood HGF and TGF-beta1 levels. In the present study we show that in FHF rats, treatment with a bioartificial liver (BAL) had similar effects. MATERIALS AND METHODS: FHF was induced in inbred Lewis rats and after 4 h, Group 1 rats were subjected to a 4-h whole blood perfusion through the BAL loaded with 3 x 10(8) microcarrier-attached syngeneic hepatocytes, whereas Group 2 control rats were treated with the BAL containing microcarriers only. RESULTS: Compared to sham-BAL-treated rats, the test rats lived longer (28 +/- 5 vs 17 +/- 2 h; P = 0.0005), had better coagulation parameters, maintained higher body core temperature, and showed decreased plasma TGF-beta1 levels. In addition, their liver remnants were HGF positive and showed increased DNA binding of transcription factors engaged in the modulation of hepatocyte proliferation (e.g., STAT3) and liver-specific gene expression (e.g., HNF1, HNF4, C/EBP). CONCLUSIONS: This study demonstrates that hepatocyte-based extracorporeal support not only can provide metabolic support by increasing the available functional liver mass but also is capable of modifying humoral and molecular mechanisms which are responsible for proliferation and organ-specific functions of residual hepatocytes.

Animals↗
PubMed1999

Transforming growth factor beta1 helps maintain differentiated functions in mitogen-treated primary rat hepatocyte cultures.

Mechanisms that control function and repair of the injured liver remain unclear. We hypothesized that after liver injury, elevated blood TGF-beta1 levels may reflect an adaptive response to help maintain differentiated functions in surviving hepatocytes affected by excessive amounts of HGF. We thus studied the effect of HGF, EGF, TGF-beta1, HGF + TGF-beta1, or EGF + TGF-beta1 on the expression of liver-enriched transcription factors and genes which remain under their regulatory activity. The peak [3H]thymidine uptake induced by 20 ng/ml of either HGF or EGF was seen after 72 h; however, DNA binding of C/EBP and HNF1 decreased already after 6 h (electrophoretic mobility shift assay). Addition of TGF-beta1 antagonized these effects. Also at the mRNA level, TGF-beta1 counteracted at one point or another the decrease in C/EBPalpha, C/EBPbeta, HNF1beta, and HNF4 expression; HNF1alpha and COUP-TF showed similar responses and, additionally, were downregulated by TGF-beta1 at 24 h (Northern blot). Albumin and apolipoprotein B mRNA levels were decreased after 24-h treatment with HGF, whereas addition of TGF-beta1 increased their levels. The same pattern was found with EGF, but not until 48 h. PEPCK mRNA was dramatically lowered with either EGF or HGF, and TGF-beta1 did not counteract these effects. Id-1 was expressed only in cultures treated for 24 and 48 h with both the mitogen (EGF, HGF) and TGF-beta1 and in those treated for 48 h with TGF-beta1 alone.

Animals↗
PubMed1998

Selective conservation of an E-protein gene promoter during vertebrate evolution.

The murine E-protein gene ME1 encodes a non-tissue-specific, helix-loop-helix transcription factor that is associated with morphological development. ME1 gene expression is regulated by a TATA-less promoter that contains multiple Sp1 consensus elements, E-boxes, and a novel transcription initiation site. In this study, we compared DNA homologous to the ME1 promoter from vertebrate species ranging from frog to human. A region of striking sequence similarity was identified in a region corresponding to the ME1 transcription initiation site (ME1 Inr). Within this region, a poly d(A) tract and a 9-bp inverted repeat (5'-GTCCGCCTG) were highly conserved in all species that were examined. Protein complexes that recognized these DNA elements were present among distant vertebrates (frog, chick, monkey and human), and were able to bend the ME1 Inr to a similar extent (approximately 60 degrees) as the previously described murine MBP alpha and MBP beta proteins. Collectively, these results suggest that an ME1 Inr-like element and its associated proteins functioned in an ancestral vertebrate more than 350 million years ago.

Animals↗
PubMed1998

Transcription initiation from a poly(dA) tract.

The mammalian ME1 gene encodes a non-tissue-specific, helix-loop-helix transcription factor that is enriched in morphogenetically active regions during development. Regulation of mouse ME1 gene expression is controlled by a novel initiator (ME1 Inr) that promotes transcription from the center of a 13 bp poly(dA) tract. We show here that the ME1 Inr autonomously directs initiation from the poly(dA) tract both in vitro and in vivo. This transcription was dependent upon two protein complexes; MBPalpha, which associated directly with the poly(dA) tract, and MBPbeta, which introduced an approximately 60 degrees bend immediately downstream of the poly(dA) tract. The MBPalpha and MBPbeta binding sites were strikingly conserved in homologous DNA from several mammalian species and the frog Xenopus laevis. These results suggest that the ME1 Inr constitutes a robust nucleation site that promotes transcription initiation in the absence of conventional promoter elements.

3T3 Cells↗
PubMed1998

Reexamination of custody restraint position and positional asphyxia.

The use of the hogtie restraint (also known as hobble or prone maximal restraint) by law enforcement and prehospital personnel has come under scrutiny because of reports of sudden deaths in persons placed in this restraint position. Some contend that this body position restricts chest and abdominal movement to the point that individuals are at risk for hypoventilatory respiratory compromise and "positional" asphyxiation. We review case reports of custody deaths in subjects placed in the hogtie position, as well as related medical literature regarding positional asphyxia. We also review the current research findings from human physiology studies that have investigated the effects of the hogtie position on respiratory and pulmonary function. We conclude that the hogtie restraint position by itself does not cause respiratory compromise to the point of asphyxiation and that other factors are responsible for the sudden deaths of individuals placed in this position.

Asphyxia↗
PubMed1997

Expanded application of selective neck dissection with regard to nodal status.

BACKGROUND: The efficacy of extending the application of selective neck dissection to include more-extensive neck disease in patients with squamous carcinoma of the upper aerodigestive tract remains controversial. METHODS: A review of all patients undergoing selective neck dissection at a single institution during a 5-year period was undertaken. The analysis was conducted on 82 patients who received 94 selective neck dissections as part of initial therapy for management of squamous carcinoma of the upper aerodigestive tract, including: oral cavity, oropharynx, larynx, and hypopharynx. RESULTS: Forty-six of the 94 dissected necks were supraomohyoid dissections, and 48 were lateral neck dissections. Sixty-five percent of patients were followed a minimum of 2 years and formed the cohort for final analysis. There were eight regional recurrences, three of which occurred in the contralateral, undissected neck. The regional recurrence rate for all patients undergoing selective neck dissection, with or without radiotherapy, according to pathologic N status was as follows: NO (1/33), 3%; N1 (1/8), 12.5%; and multiple positive nodes (3/26), 11.5%. A comparison of recurrence rates with respect to extent of neck disease (N0-N1 versus multiple positive nodes) for both types of neck dissection did not demonstrate significant differences; supraomohyoid neck dissection, p < .5; lateral neck dissection, p < .25. CONCLUSIONS: There exists an expanded role for selective neck dissection in selected patients with primary squamous cell carcinoma of the upper aerodigestive tract and multiple N+ cervical disease. The selection of patients who are candidates for selective lymphadenectomy should be based on pathoanatomic considerations with reference to the primary site of tumor and demonstrated level(s) of metastatic involvement.

Aged↗
PubMed1997

Restraint position and positional asphyxia.

STUDY OBJECTIVE: To determine whether the "hobble" or "hog-tie" restraint position results in clinically relevant respiratory dysfunction. METHODS: This was an experimental, crossover, controlled trial at a university-based pulmonary function laboratory involving 15 healthy men ages 18 through 40 years. Subjects were excluded for a positive urine toxicology screen, body mass index (BMI) greater than 30 kg/m2, or abnormal screening pulmonary function testing (PFT). Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and maximal voluntary ventilation (MVV) were obtained with subjects in the sitting, supine, prone, and restraint positions. After a 4-minute exercise period, subjects rested in the sitting position while pulse, oxygen saturation, and arterial blood gases were monitored. The subjects repeated the exercise, then were placed in the restraint position with similar monitoring. RESULTS: There was a small, statistically significant decline in the mean FVC (from 5.31 +/- 1.01 L [101% +/- 10.5% of predicted] to 4.60 +/- .84 L [88% +/- 8.8% of predicted]), mean FEV1 (from 4.31 +/- .53 L [103% +/- 8.4%] to 3.70 +/- .45 L [89% +/- 7.7%]), and mean MVV (from 165.5 +/- 24.5 L/minute [111% +/- 17.3%] to 131.1 +/- 20.7 L/minute [88% +/- 16.6%]), comparing sitting with restraint position (all, P < .001). There was no evidence of hypoxia (mean oxygen tension [PO2] less than 95 mm Hg or co-oximetry less than 96%) in either position. The mean carbon dioxide tension (PCO2) for both groups was not different after 15 minutes of rest in the sitting versus the restraint position. There was no significant difference in heart rate recovery or oxygen saturation as measured by co-oximetry and pulse oximetry. CONCLUSION: In our study population of healthy subjects, the restraint position resulted in a restrictive pulmonary function pattern but did not result in clinically relevant changes in oxygenation or ventilation.

Adolescent↗
PubMed1997

Embryonic expression and evolution of duplicated E-protein genes in Xenopus laevis: parallels with ancestral E-protein genes.

E-proteins comprise a subfamily of helix-loop-helix transcription factors that have been identified in arthropods and several chordate taxa. In mammals, there are three classes of E-protein genes (E2A, E2-2, and HEB) that encode related, and often interchangeable, gene products. We have determined that the clawed frog Xenopus laevis contains twice the number of transcriptionally active E-protein genes when compared with other vertebrate species. Based upon genomic Southern blots and nucleotide sequence comparisons, it is likely that the additional X. laevis genes arose from tetraploidization. During embryogenesis, XE2A (homologue of mammalian E2A) transcripts were broadly expressed in anterior and posterior regions of the embryo while homologues of E2-2 (XE2.2) and HEB (XE1.2) appeared in vertebrate-specific structures including the pineal gland, olfactory bulb, and brachial arches. A phylogenetic analysis of these genes and other known metazoan E-proteins suggests that there were two periods of marked E-protein gene expansion; one that predated the radiation of vertebrates, and the other that coincided with Xenopus tetraploidization. Both of these periods were characterized by the rapid evolution of E2-2 and HEB-class genes, but not of E2A. We propose that the former genes acquired new or specialized roles during early chordate evolution and also more recently in Xenopus, as reflected by the stereotypic expression patterns of these genes during X. laevis development.

Amino Acid Sequence↗
PubMed1997

A case of spinal cord decompression sickness presenting as partial Brown-Sequard syndrome.

Type II decompression sickness (DCS) usually manifests as myelopathy; however, there are no reports of Brown-Sequard syndrome in association with diving accidents. We report a 35-year-old man who developed type II DCS presenting as partial Brown-Sequard syndrome. MRI of the thoracic spine revealed two punctate foci of increased signal intensity in the right T6 spinal cord.

Adult↗
PubMed1996

Overexpression of E2F1 in astrocytes leads to neoplastic transformation and changes in expression of retinoblastoma family members.

Overexpression of mouse E2F1 full-length but not truncated forms results in neoplastic transformation of astrocytes in vitro. This neoplastic transformation is accompanied with changes in cell morphology and expression of cell cycle regulators. Transformed astrocytes have higher expression of cdk2, pRb, and p107 than control astrocytes. However, expression of glial fibrillary acidic protein (GFAP) and p130 is reduced in transformed astrocytes.

Animals↗