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Biomedical subjects

K Roberts

Publications and source records attributed to K Roberts.

At least 91 records · Page 5Linked to original sources
PubMed1997

CBP/p300 as a co-factor for the Microphthalmia transcription factor.

The Microphthalmia basic-Helix-Loop-Helix-Leucine Zipper (bHLH-LZ) transcription factor (Mi) plays a crucial role in the genesis of melanocytes; mice deficient for a functional (Microphthalmia) gene product lack all pigment cells. We show here that the Mi activation domain resides N-terminal to the DNA-binding domain and that as little as 18 amino acids are sufficient to mediate transcription activation. The minimal activation region of Mi is highly conserved in the related transcription factor TFE3 and is predicted to adopt an amphipathic alpha-helical conformation. This region of Mi is also highly conserved with a region of E1A known to be essential for binding the CBP/p300 transcription cofactor. Consistent with these observations, the Mi activation domain can interact in vitro with CBP specifically through a region of CBP required for complex formation with E1A, P/CAF and c-Fos, and anti p300 antibodies can co-immunoprecipitate Mi from both melanocyte and melanoma cell lines. In addition, co-transfection of a vector expressing CBP2 (aas 1621-1891) fused to the VP16 activation domain potentiated the ability of Mi to activate transcription, confirming the significance of the CBP-Mi interaction observed in vitro. These data suggest that transcription activation by Mi is achieved at least in part by recruitment of CBP. The parallels between transcription regulation by Microphthalmia in melanocytes and MyoD in muscle cells are discussed.

Adenovirus E1A Proteins↗
PubMed1997

Treatment of recurrent pelvic and selected primary gynecologic malignancies with 241Am.

The purpose of this study was to update the experience and demonstrate the effectiveness and limitations of 241Am applicators for previously irradiated patients and for selected patients with primary gynecologic malignancies. Between October 1986 and May 1994, 30 patients were treated with 241Am. The median patient age was 68 years, ranging from 41 to 91 years. Patients were retrospectively categorized by treatment intent, i.e., palliative vs. curative. Patients undergoing curative therapy were further classified as to whether 241Am brachytherapy was directed at microscopic residua after surgery or to gross primary tumor. Of the 30 patients, 18 had recurrent pelvic malignancies from various primary sites and were reirradiated with 241Am for palliation. Six patients had microscopic disease after surgical resection and were managed with postoperative radiotherapy (RT) that included 241Am. Six patients had gynecologic cancers managed with primary RT that included treatment with 241Am. Overall, 50% (9/18) of the patients with recurrent pelvic malignancies were locally controlled after reirradiation with 241Am. Including surgical salvage, the ultimate local control rate was 61% (11/18). Postoperative 241Am with or without external beam radiation therapy (XRT) was effective in 83% (5/6) of the patients with microscopic disease. Including surgical salvage, 100% (6/6) of the patients were ultimately free of disease. Fifty percent (3/6) of the patients treated with primary RT that included 241Am brachytherapy experienced local control. Including surgical salvage, 67% (4/6) of the patients were ultimately controlled with 241Am. In conclusion, reirradiation utilizing 241Am was effective in palliating patients with recurrent pelvic malignancies. 241Am was effective in 83% (5/6) of the patients with microscopic disease managed with postoperative RT. 241Am was of marginal benefit in patients with gynecologic tumors managed with primary RT.

Aged↗
PubMed1997

A comparison of physiologically based pharmacokinetic model predictions and experimental data for inhaled ethanol in male and female B6C3F1 mice, F344 rats, and humans.

Ethanol is added to unleaded gasoline as an oxygenate to decrease carbon monoxide automobile emissions. This introduces inhalation as a new possible route of environmental exposure to humans. Knowledge of the pharmacokinetics of inhaled ethanol is critical for adequately assessing the dosimetry of this chemical in humans. The purpose of this study was to characterize the pharmacokinetics of inhaled ethanol in male and female B6C3F1 mice and F344 rats and to develop a physiologically based pharmacokinetic (PBPK) model for inhaled ethanol in mice, rats, and humans. During exposure to 600 ppm for 6 hr, steady-state blood ethanol concentrations (BEC) were reached within 30 min in rats and within 5 min in mice. Maximum BEC ranged from 71 microM in rats to 105 microM in mice. Exposure to 200 ppm ethanol for 30 min resulted in peak BEC of approximately 25 microM in mice and approximately 15 microM in rats. Peak BEC of about 10 microM were measured following exposure to 50 ppm in female rats and male and female mice, while blood ethanol was undetectable in male rats. No sex-dependent differences in peak BEC at any exposure level were observed. Species-dependent differences were found following exposure to 200 and 600 ppm. A blood flow limited PBPK model for ethanol inhalation was developed in mice, rats, and humans which accounted for a fractional absorption of ethanol. Compartments for the model included the pulmonary blood and air, brain, liver, fat, and rapidly perfused and slowly perfused tissues. The PBPK model accurately simulated BEC in rats and mice at all exposure levels, as well as BEC reported in human males in previously published studies. Simulated peak BEC in human males following exposure to 50 and 600 ppm ranged from 7 to 23 microM and 86 and 293 microM, respectively. These results illustrate that inhalation of ethanol at or above the concentrations expected to occur upon refueling results in minimal BEC and are unlikely to result in toxicity.

Administration, Inhalation↗
PubMed1997

Ultrastructural analysis of leaf trichome plasmodesmata reveals major differences from mesophyll plasmodesmata.

Functional studies on molecular transport through plasmodesmata in leaf mesophyll and trichome cells revealed significant differences in their basal size-exclusion limits and their response to microinjected tobacco mosaic virus movement protein (E. Waigmann et al., 1994, Proc. Natl. Acad. Sci. USA 91: 1433-1437; E. Waigmann and P. Zambryski, 1995, Plant Cell 7; 2069-2079). To address the basis for these functional differences, Nicotiana clevelandii trichome and mesophyll plasmodesmata were compared ultrastructurally. Trichome plasmodesmata increase in ultrastructural complexity from the tip to the base cell. Their neck regions, thought to control molecular traffic through plasmodesmata, are clearly distinct from necks of mesophyll plasmodesmata. In contrast to the electrondense desmotubular area in mesophyll plasmodesmata, trichome plasmodesmata contain an electron-translucent circle in their center, surrounded by an electrondense ring. This latter ring is connected to the inner leaflet of the plasma membrane by multiple spokes or filaments. Two monoclonal antibodies raised against a maize plasmodesmal protein preparation (A. Turner et al., 1994, J Cell Sci. 107: 3351-3361) interact with both trichome and mesophyll N. clevelandii plasmodesmata. Based on the localization pattern and the high degree of cross-reactivity, both antibodies likely recognize a conserved structural component of plasmodesmata, and may be useful to mark plasmodesma in a variety of plants and tissues.

Cell Communication↗
PubMed1997

Cultured nasal polyps from nonatopic and atopic patients release RANTES spontaneously and after stimulation with phytohemagglutinin.

BACKGROUND: Eosinophil infiltration of tissue is a hallmark of nasal polyposis in both nonatopic and atopic patients. These cells are thought to play a key role in the nasal polyp inflammatory process. OBJECTIVE: The objective of this study was to investigate whether cultured nasal polyps derived from nonatopic and atopic patients release RANTES both spontaneously and after phytohemagglutinin (PHA) stimulation. METHODS: Nasal polyps were obtained from 12 subjects (6 nonatopic and 6 atopic), cut into 2 to 3 mm large specimens, and cultured for 48 hours with or without PHA. RANTES was measured in the culture supernatant by ELISA (R&D Systems, U.K.). RESULTS: Immunoreactive RANTES was found to be present in the culture supernatant of nasal polyps derived from both nonatopic and atopic patients with no difference between the two groups (median: 3.8 vs 2.9 pg/mg/ml). On incubation with PHA, nasal polyps from both nonatopic and atopic patients released sevenfold and 11-fold greater amounts of RANTES than unstimulated samples. As determined by immunohistochemistry, RANTES was localized to the vascular endothelium in nasal polyps from both groups of patients. CONCLUSIONS: This study demonstrates that cultured nasal polyps derived from both nonatopic and atopic patients release RANTES spontaneously and after PHA stimulation. This observation and the finding that RANTES is present in nasal polyp endothelial cells suggest that this chemokine may be an important mediator of eosinophil and lymphocyte recruitment in both nonatopic and atopic nasal polyposis.

Adult↗
PubMed1997

A preliminary account of the effect of otitis media on 15-month-olds' categorization and some implications for early language learning.

In the present study, 24 infants 14 to 16 months old (M = 15.3 months) with a history of otitis media (OM) and tube placement were tested for categorical responding within a visual familiarization-discrimination paradigm (cf. Roberts & Jacob, 1991; Roberts, 1995a). Sixteen infants were, on average, 4.6 months post-tubes. At the time of testing, hearing was reported to be normal. During both the familiarization and testing phases, reiterant speech ulterances (e.g., "ti ti the sasasa," "bo bo the sasasa," "gu gu the sasasa," "sasasa") were randomly presented contingent on infants' looking at line drawings of selected animals. The inclusion of the article the in these utterances provides an important grammatical cue signaling an upcoming noun label. Using these same procedures, utterances, and animal stimuli, normal-hearing 15-month-olds without a reported history of OM had categorized successfully in two previous experiments. In contrast, the OM infants did not respond categorically under these conditions. This suggests that even mild hearing loss may adversely affect categorical responding under specific input conditions and that this effect may persist after normal hearing is restored. A plausible account is that fluctuating hearing loss may cause the low-phonetic-substance article to vacillate above and below some attentional threshold. The resulting inconsistency in the article's availability would disrupt the co-occurrence relation between the article and cues already connected to joint attentional/referential interactions and categorical treatment of objects (cf. Roberts, 1995a). Such a disruption has implications for the acquisition of words and other aspects of language.

Child Language↗
PubMed1997

The COW1 locus of arabidopsis acts after RHD2, and in parallel with RHD3 and TIP1, to determine the shape, rate of elongation, and number of root hairs produced from each site of hair formation.

Two recessive mutant alleles at CAN OF WORMS1 (COW1), a new locus involved in root hair morphogenesis, have been identified in Arabidopsis thaliana L. Heynh. Root hairs on Cow1- mutants are short and wide and occasionally formed as pairs at a single site of hair formation. The COW1 locus maps to chromosome 4. Root hairs on Cow1- plants form in the usual positions, suggesting that the phenotype is not the result of abnormal positional signals. Root hairs on Cow1- roots begin hair formation normally, forming a small bulge, or root hair initiation site, of normal size and shape and in the usual position on the hair-forming cell. However, when Cow1- root hairs start to elongate by tip growth, abnormalities in the shape and elongation rate of the hairs become apparent. Genetic evidence from double-mutant analysis of cow1-1 and other loci involved in root hair development supports our conclusion that COW1 is required during root hair elongation.

Alleles↗
PubMed1997

Allergen-induced release of GM-CSF and IL-8 in vitro by nasal polyp tissue from atopic subjects prolongs eosinophil survival.

Eosinophilia is a feature of nasal polyposis. The aim of this study was to determine the role of cytokines and allergen in maintaining the eosinophilic infiltrate in this condition. Polyp fragments from house dust mite (HDM)-sensitive atopic individuals and nonatopic individuals were cultured in the presence of HDM, or phytohaemagglutinin (PHA) or culture medium alone. Culture supernatants were assayed for interleukins (IL) 3, 5, and 8 and granulocyte macrophage colony stimulating factor (GM-CSF), and eosinophil survival enhancing activity (ESEA) in vitro. Significant ESEA was produced spontaneously. When polyp tissue from atopics, but not from nonatopics, was stimulated with allergen for 2 days there was a further increase in ESEA associated with a median 12 and fourfold increase in IL-8 and GM-CSF, respectively. This increased ESEA was markedly reduced with anti-GM-CSF and, to a lesser extent, anti-IL-8 blocking antibodies. When stimulated with PHA, polyp tissue from atopic subjects also produced increased ESEA, implicating possible T-cell involvement. This was associated with a small (twofold), but significant, increase in IL-8 and a less consistent increase in GM-CSF. However, anti-IL-8 or anti-GM-CSF blocking antibodies failed to reduce the ESEA in these supernatants, suggesting involvement of other mechanisms. This study suggests that in sensitized individuals, allergen may contribute to polyp eosinophilia by stimulating the production of granulocyte/macrophage colony stimulating factor and interleukin 8.

Allergens↗
PubMed1997

Structural and genetic analysis of epidermal cell differentiation in Arabidopsis primary roots.

In a screen designed to identify genes in the specification of epidermal cell fate in Arabidopsis primary roots we have isolated 8 new mutants that fall into 6 complementation groups corresponding to the 'root hairless' genes RHL1, RHL2 and RHL3 and the 'ectopic root hair' genes ERH1, ERH2 and ERH3. The erh2 mutant is allelic to pom1, a conditional root expansion mutant, and reveals a possible link between epidermal root hair initiation and radial cell expansion. Apart from erh1 the mutants also show defects in shoot development, indicating a complex role for the affected genes. Mutant phenotypes in the patterning and shape of leaf trichomes in rhl1, rhl2, rhl3 and erh3 were particularly obvious. The root hairless mutants are only partly responsive to increased ethylene concentrations, while the ectopic root hair mutants are fully responsive to reduced concentrations of ethylene, a permissive regulator of root hair initiation. This result and the analysis of double mutants suggest a complex pathway leading to root hair initiation that requires the RHL and ERH genes for correct differentiation.

Arabidopsis↗
PubMed1996

Complete gene map of the plastid-like DNA of the malaria parasite Plasmodium falciparum.

Malaria parasites, and other parasitic protists of the Phylum Apicomplexa, carry a plastid-like genome with greatly reduced sequence complexity. This 35 kb DNA circle resembles the plastid DNA of non-photosynthetic plants, encoding almost exclusively components involved in gene expression. The complete gene map described here includes genes for duplicated large and small subunit rRNAs, 25 species of tRNA, three subunits of a eubacterial RNA polymerase, 17 ribosomal proteins, and a translation elongation factor. In addition, it codes for an unusual member of the Clp family of chaperones, as well as an open reading frame of unknown function found in red algal plastids. Transcription is polycistronic. This plastid-like DNA molecule is conserved in several genera of apicomplexans and is conjectured to have been acquired by an early progenitor of the Phylum by secondary endosymbiosis. The function of the organelle (plastid) carrying this DNA remains obscure, but appears to be specified by genes transferred to the nucleus.

Amino Acid Sequence↗
PubMed1996

A clarification of the Russell, Neuringer, and Goldstein Process Key: implications for outcome.

The purpose of this study was that of attempting to clarify discrepant results regarding classificatory accuracy of the Russell, Neuringer and Goldstein (1970) Process Key. The Process Key is the component of the neuropsychological keys that classifies cases as having recently or remotely acquired brain damage on the basis of level of performance and severity of lateralizing signs. A correct classification of acute brain damage occurs when onset of illness began within 3 months of time of testing. A study of stroke patients indicated that time since onset is an inadequate criterion for producing a satisfactory classificatory level, but time of onset in combination with type of stroke was associated with a high degree of classificatory accuracy. In particular, patients with recent thrombotic/hemorrhagic type strokes were classified as acute with a very high accuracy level, but the classification was substantially less accurate for recent stroke patients with other types of stroke, and for cases that were not of recent onset.

Journal Article↗
PubMed1995

The development of cell pattern in the root epidermis.

The root epidermis of most angiosperms is composed of a patterned array of hair and non-hair cells. Hair cells may develop randomly in any location in the epidermis (type 1), from specialized cells that form as result of an asymmetric cell division in a mother cell (type 2) or cells may be arranged in files of one cell type or the other (type 3). The development of the epidermis in Arabidopsis has been examined in detail and corresponds to type 3 epidermal development. A combination of physiological and genetic observations indicates that ethylene is a positive regulator of root hair differentiation. Differential exposure of epidermal cells to ethylene as a result of the cellular geometry of the root may account for the wild-type epidermal pattern.

Arabidopsis↗
PubMed1995

Clinical implications of patients' knowledge.

We evaluated the effectiveness of current strategies for educating patients in routine clinical practice in three related studies. (1) A study of overall knowledge in 100 patients with rheumatoid arthritis (RA) and osteoarthritis (OA) showed knowledge of diagnosis and treatment effects were high (86% and 83% respectively) but only a minority (37%) were well informed about side effects. (2) Patients' detailed knowledge of drug therapy was assessed in 50 RA and OA patients. Between 56%-92% knew why drugs were given, their use and their likely effects. But many patients were unaware of the main adverse reactions and also how to avoid or limit them. (3) The relationship of patient education to overall disease management was evaluated in 89 RA patients with 5-10 years disease duration using validate guidelines for specialist care. Those patients who had been give inadequate education about drug therapy had a reduced level of overall care. Although education is considered important by patients, it is often inadequate, and this is associated with a less effective overall treatment.

Aged↗
PubMed1995

Plant development: pulled up by the roots.

Recent advances in the study of root development in Arabidopsis have begun to yield mechanistic insights into the processes that underpin morphogenesis, pattern formation and cell differentiation in plants. The most exciting feature of these advances is that, as a consequence of the simple and largely invariant cellular architecture of the root, the processes can be studied at a cellular level. Nevertheless, it is clear that although the cell lineages of the root are relatively invariant, we have no evidence that lineage per se is an important regulator of development. Instead, all the evidence indicates that the positional regulation of inductive cues is of primary importance. The availability of new root mutants is alerting us to the complexity of the contribution of cell size and cell expansion to plant development.

Arabidopsis↗