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Biomedical subjects

A Yen

Publications and source records attributed to A Yen.

At least 19 recordsLinked to original sources
PubMed1995

Herpesvirus-like DNA sequences in non-Kaposi's sarcoma skin lesions of transplant patients.

Herpesvirus-like DNA sequences (KSHV) have been reported to be associated with various forms of Kaposi's sarcoma (KS). To determine if KSHV was associated with other proliferative skin lesions from non-AIDS immunocompromised patients, 33 skin lesions (basal cell carcinomas, squamous cell carcinomas, actinic keratoses, verruca vulgaris, atypical squamous proliferations, and seborrhoeic keratosis) from 4 organ-transplant patients receiving immunosuppressive therapy were tested for KSHV by PCR. KSHV sequences were detected in 82% of these skin lesions. Our results suggest that KSHV is associated with lesions other than KS in non-AIDS immunocompromised patients, and may also be involved in the pathogenesis of the various forms of proliferative skin lesions from organ-transplant patients.

Base Sequence↗
PubMed1995

RB phosphorylation in sodium butyrate-resistant HL-60 cells: cross-resistance to retinoic acid but not vitamin D3.

To examine the potential coupling between inducible cellular changes in RB (retinoblastoma) tumor suppressor protein phosphorylation and ability to G0 growth arrest and differentiate, HL-60 promyelocytic leukemia cells were cultured in incremental sodium butyrate (NaB) concentrations and thereby made resistant to the growth inhibitory effects of sodium butyrate, which normally induces G0 arrest and monocytic differentiation in wild type HL-60 cells. The resistant cells were also unable to differentiate in response to NaB, indicating that a regulatory function controlling both G0 growth arrest and differentiation had been affected. The induced resistance was not genetic in origin since the cells regained the ability to G0 arrest and differentiate after being recultured in medium free of sodium butyrate for only three days. The resistant cells had similar cell cycle phase durations as the original wild type cells. The resistant cells retained the ability to both G0 arrest and differentiate in response to 1,25-dihydroxy vitamin D3 (VD3), normally an inducer of G0 arrest and monocytic differentiation in wild type cells. However, they were cross-resistant to retinoic acid (RA), another ligand for the same steroid thyroid hormone receptor family, which induces G0 arrest and myeloid differentiation in wild type cells. The ability to G0 arrest and phenotypically differentiate in response to RA were both grossly impaired. Unlike wild type cells which undergo early down-regulation and then hypophosphorylation of the RB protein when induced to differentiate, in resistant cells, hypophosphorylation of RB in response to NaB was grossly retarded. These changes in RB protein occurred faster when the cells were treated with VD3. In contrast, the changes in RB phosphorylation occurred significantly slower when the cells were treated with RA. The results suggest a coupling between the ability to G0 growth arrest and phenotypically convert and the ability to hypophosphorylate RB.

Butyrates↗
PubMed1995

Elastoderma.

Elastoderma is an exceedingly rare condition that is characterized clinically as an acquired localized laxity of skin resembling cutis laxa and histologically as an excessive accumulation of pleomorphic elastic structures within the dermis. We report the case of a 27-year-old white man with a 2-year history of lax, extensible, wrinkled skin with areas of protrusion and ulceration localized to the anterior aspect and back of the neck. Histologic examination of specimens from the affected area revealed increased masses of intertwined thin, elastic fibers without calcification in the papillary and upper reticular dermis. Transmission and scanning electron microscopy demonstrated irregular deposition of elastic material at the periphery of elastic tissue fibers, with grapelike globular structures. To our knowledge, this is the second reported case of elastoderma.

Adult↗
PubMed1995

Development, characterization, and initial evaluations of S1. A new chromogenic cephalosporin for beta-lactamase detection.

A novel, chromogenic cephalosporin reagent (S1) for beta-lactamase testing was produced that shares physicochemical characteristics with nitrocefin (formerly 87/312). S1 and nitrocefin in a disk-testing format for beta-lactamase performed at 100% agreement for detecting enzyme-producing isolates of Bacteroides fragilis group, Haemophilus influenzae, Moraxella catarrhalis, Neisseria gonorrhoeae, Staphylococcus aureus, and selected Enterobacteriaceae. The time required to achieve an initial color change or a strong positive reaction was comparable for both chromogenic reagents for all organisms except the Gram-positive species. S1 reaction times were approximately 50% faster than nitrocefin for beta-lactamase-positive enterococci and S. aureus. These results from the developmental studies and a commercially prepared disk lot indicate that S1 is a promising beta-lactamase disk test reagent with the ability to detect all significant enzyme-producing species strains, some significantly earlier than the nitrocefin disk method.

Bacteria↗
PubMed1994

Characterization of a vitamin D3-resistant human chronic myelogenous leukemia cell line.

A variant of the chronic myelogenous leukemia cell line, RWLeu-4, that is resistant to the antiproliferative effects of vitamin D3 was established. Although RWLeu-4 proliferation is inhibited by 1 nmol/L vitamin D3, the resistant cells (JMRD3) continue to proliferate in the presence of 100 nmol/L vitamin D3. Both cells express similar patterns of differentiation-specific antigens after treatment with vitamin D3, and both express the retinoblastoma gene product (p110Rb). Vitamin D3 treatment of the sensitive RWLeu-4 cells decreased the level of the p110Rb protein, as well as its phosphorylation. In contrast, vitamin D3 treatment of JMRD3 had no effect on p110Rb expression or phosphorylation. Both RWLeu-4 and JMRD3 express similar vitamin D3 receptors and vitamin D3-inducible enzyme activities. Differences were detected in the DNA binding characteristics of the vitamin D3 receptors as determined by electrophoretic mobility shift studies. However, sequence analysis of the DNA-binding domain and immunoblot analysis showed no differences in the receptors. We conclude that some process subsequent to vitamin D3 receptor activation is altered in JMRD3 that partially separates vitamin D3-induced inhibition of proliferation from the induction of differentiation.

Base Sequence↗
PubMed1994

Inhibition of human peripheral blood lymphocyte function by protoporphyrin and longwave ultraviolet light.

Modulation of immunologic effector cells by exogenous photoactive substances has been advanced as an underlying mechanism for the efficacy of various photochemotherapeutic regimens. It is also possible that endogenous photosensitizers, such as protoporphyrin, could similarly modify the function of immune cell types. We examined the effects of protoporphyrin plus longwave UV light on the ability of human PBL to proliferate in response to mitogens. Noncytotoxic dosages of protoporphyrin plus UV light suppressed PHA-stimulated proliferation of both PBMC and enriched T cells. CD8+ cells were more sensitive to this inhibitory effect than CD4+ cells. The inhibitory effect was also observed when proliferation was induced by the combination of a phorbol ester and ionomycin. Inhibition of PBMC proliferation was associated with inhibition of IL-2 secretion but proliferation was not restored with exogenous IL-2. Instead, the effect of protoporphyrin plus UV light may be on IL-2R. Cells treated with protoporphyrin and UV light did not display the increase in CD25 and the beta-chain of the IL-2R induced by PHA in control cells. In contrast to the effects of protoporphyrin and UV light on IL-2 and IL-2R alpha-chain protein expression, the accumulation of mRNA for these proteins induced by PHA was unaffected. None of the effects of protoporphyrin plus UV light on lymphocytes were observed in control experiments where cells were treated with either protoporphyrin or UV light alone. We conclude that biologically relevant dosages of protoporphyrin and UV light modify the function of circulating lymphocytes.

Base Sequence↗
PubMed1994

Predesquamin extends maturation of cultured keratinocytes.

Predesquamin is a glycoprotein that we have isolated from human epidermis. Its monospecific polyclonal antibody immunolocalizes to the lower stratum corneum. We have previously found that it is not expressed ordinarily in primary keratinocyte cultures, but that it is expressed in a serum-containing medium that is supplemented with interferon-gamma. Under these conditions, we observed larger outer squames and a more mature pattern of desquamation. We now demonstrate, by adding predesquamin directly to the culture medium without the cytokine, that the morphological changes are caused by predesquamin (and the role of IFN-gamma in the previous experiment was to stimulate the expression of predesquamin).

Antibodies↗
PubMed1994

Enhanced cell differentiation when RB is hypophosphorylated and down-regulated by radicicol, a SRC-kinase inhibitor.

Radicicol, an inhibitor of src or src-like kinases, causes hypophosphorylation and down-regulation of the RB retinoblastoma tumor suppressor protein in HL-60 human promyelocytic leukemia cells. Both of these changes in the RB protein typically are associated with myeloid or monocytic differentiation of these cells induced by retinoic acid or 1,25-dihydroxy vitamin D3. When added with either inducer, radicicol caused the typically induced myeloid or monocytic differentiation of these cells to be accelerated. By itself radicicol caused a transient inhibition of G1 to S transit, but did not cause phenotypic conversion. The down-regulation and dephosphorylation of RB by radicicol may thus facilitate cell differentiation.

Calcitriol↗
PubMed1994

Late dephosphorylation of the RB protein in G2 during the process of induced cell differentiation.

The cell cycle phase-specific phosphorylation status of the RB protein (retinoblastoma tumor suppressor gene product) during an elicited cellular program of G0 arrest and cell differentiation was characterized. The RB protein phosphorylation state is presumed to be an important determinant of cell proliferation or arrest. The cell cycle phase specificity of RB protein phosphorylation and dephosphorylation during HL-60 human leukemia cell proliferation and differentiation was determined using DNA-based fluorescence-activated cell sorting and Western analysis. The RB protein in proliferating G1 cells was phosphorylated, but at a relatively low level. The extent of phosphorylation increased in S phase cells and was maximum in G2 + M cells. After the cells were treated with retinoic acid or 1,25-dihydroxy vitamin D3, they began to accumulate in G1/0 and phenotypically convert. Significant unphosphorylated RB protein did not appear until after the first cells had arrested and differentiated. Dephosphorylation of the RB protein was first apparent at the beginning of G2 in the remaining cycling cells after onset of arrest and differentiation had already occurred. By the time the remaining cycling cells had divided and arrested, resulting in G0 cells, a majority of RB protein was dephosphorylated, but some remained phosphorylated. The data indicate that dephosphorylation of RB does not determine residence in G1/0. Rather dephosphorylation appears as one relatively late-occurring component of the metabolic cascade culminating in G0-arrested, phenotypically differentiated cells. Dephosphorylated RB appears as a feature of differentiated cells. The data are consistent with a role for hypophosphorylated RB not so much in deriving, but in possibly sustaining the differentiated state.

Blotting, Western↗
PubMed1994

Effect of dietary omega-3 and omega-6 fatty acid sources on PUVA-induced cutaneous toxicity and tumorigenesis in the hairless mouse.

Because of concern about psoralen-induced phototoxicity and photocarcinogenesis, we investigated the effects of dietary lipids in a mouse model in which 8-methoxypsoralen (8-MOP) and UVA (PUVA) therapy has been shown to be carcinogenic. SKH-Hr-1 hairless albino mice were fed diets containing either omega-3 or omega-6 fatty-acid sources (menhaden oil and corn oil, respectively). After 2 weeks on the diets, the mice were treated topically with 8-MOP and then exposed to UVA (5 J/cm2). Mice receiving the omega-3 fatty-acid source exhibited a marked decrease in inflammatory response and a more rapid repair, as expressed both grossly and microscopically. In support of the latter response, i.e. repair, ornithine decarboxylase activity was about 20% greater in animals receiving the omega-3 fatty-acid source. The effects of the dietary fatty acid sources on PUVA tumorigenesis were examined in long-term studies in which animals were treated topically with 0.01% 8-MOP thrice weekly after which they were exposed to UVA (1 J/cm2). These studies indicated that a dietary lipid rich in omega-3 fatty acid and known to exhibit anti-inflammatory properties can markedly ameliorate the course of PUVA toxicity but does not impede the course of PUVA tumorigenesis.

Animals↗
PubMed1994

Expression of activated RAF accelerates cell differentiation and RB protein down-regulation but not hypophosphorylation.

Expression of an activated raf transgene accelerated the terminal myeloid differentiation of HL-60 human promyelocytic leukemia cells induced by retinoic acid. A similar result was obtained when 1,25-dihydroxyvitamin D3 was used to induce monocytic differentiation. The stable transfectants were derived by transfecting HL-60 cells with DNA encoding an N-terminal truncated raf-1 protein. In normal HL-60 cells retinoic acid is known to induce a colony-stimulating factor-1 (CSF-1)-dependent metabolic cascade culminating in G0 arrest and phenotypic conversion. Early in this cascade, expression of the RB tumor suppressor gene product is down-regulated. A progressive redistribution of the form of the protein from largely hyperphosphorylated protein to the hypophosphorylated form begins later with G0 arrest and differentiation. In the activated raf-transfected cells, RB down regulation occurred more rapidly, consistent with accelerated differentiation. But the conversion to the hypophosphorylated form was not accelerated and occurred after G0 arrest and phenotypic conversion to myeloid differentiated cells. Thus raf activation appears to be a component of the induced metabolic cascade culminating in terminal differentiation. In this cascade raf activation promotes RB down-regulation. The data are consistent with a model in which raf is an effector of the CSF-1-dependent metabolic cascade which culminates in terminal cell differentiation, and RB downregulation is one of the downstream consequences of RAF action. Furthermore, they indicate that RB down-regulation may be an essential component of the cellular processes causing G0 arrest and differentiation, but RB hypophosphorylation is more likely a consequence thereof and not a cause.

Cell Differentiation↗
PubMed1994

Character of shed blood in cardiac and thoracic surgery patients: implications for reinfusion.

OBJECTIVE: To determine whether the independently observed increase in the levels of cardiac enzymes in peripheral blood can be accounted for by elevations from postoperative shed-blood reinfusion in patients who have undergone cardiac or thoracic operations. DESIGN: Prospective, case-controlled study. SETTING: A cardiothoracic surgery unit at a university referral centre. PATIENTS: Thirty-four consecutive patients who underwent cardiac or thoracic surgery within a 3-week period. INTERVENTIONS: Coronary artery revascularization (23 patients), cardiac valve replacement or repair (4) and lung resection (7). MAIN OUTCOME MEASURES: Determination of levels of cardiac enzymes and isoenzymes in samples of peripheral and shed blood. Statistical comparison was by paired t-tests within groups and by unpaired t-tests between groups. RESULTS: Serum levels of creatine kinase, lactic dehydrogenase and aspartate aminotransferase were significantly (p < 0.001) elevated in samples of shed blood compared with peripheral blood in all groups. The elevations were found to be related to skeletal muscle injury and were not of cardiac origin. In the absence of myocardial infarction, cardiac isoenzyme levels were significantly (p < 0.001) elevated in the peripheral blood of cardiac surgery patients compared with that of thoracic surgery patients. CONCLUSION: Reinfusion of shed blood will result in elevated levels of cardiac enzymes in peripheral blood but will not increase the percentage of isoenzymes.

Alanine Transaminase↗
PubMed1992

Regulation of cell proliferation: late down-regulation of c-myb preceding myelo-monocytic cell differentiation.

Expression of the c-myb nuclear oncogene during the cell proliferation and differentiation of HL-60 human promyelocytic leukemia cells was characterized and compared to the expression of c-fos, another nuclear oncogene with transcriptional regulatory activity. During progression through the cell cycle, the amount of c-myb protein increased. The increase was commensurate with total cell size, thus preserving the relative abundance of c-myb protein present at the onset of the cell cycle. In HL-60 cells, the induced metabolic cascade leading to terminal myeloid or monocytic differentiation segregates into two steps occurring over two division cycles. Expression of c-myb did not diverge from the control until late in this metabolic cascade when it declined prior to onset of terminal differentiation. This course of expression was similar for both the retinoic acid induced myeloid or the 1,25-dihydroxy vitamin D2 induced monocytic terminal differentiation of the cells. Bromodeoxyuridine, which induces proliferative arrest but not phenotypic differentiation of these cells, induced the same course of c-myb expression as the inducers of terminal differentiation. The same course of c-myb expression with growth arrest induced by these three different means is consistent with a potential proliferation regulatory role for c-myb in late but not early events leading to terminal differentiation. The dynamics of c-myb expression during this process were qualitatively, but not quantitatively, similar to the course of c-fos expression. Thus, taken with previous results, then amongst the nuclear oncogenes or tumor suppressor genes, c-myc, RB, c-fos, and c-myb, only c-myc and RB expression exhibit early regulation during induced HL-60 cell differentiation.

Bromodeoxyuridine↗
PubMed1992

IgE and adenosine 5' triphosphate receptors on immature murine mast cells are functionally linked to signal transduction mechanisms.

Calcium mobilization in response to IgE-receptor cross-linking by antigen was assessed in immature murine mast cells cultured from bone marrow to determine whether the early expression of IgE receptors on such cells may be of functional significance. IgE receptors were expressed by approximately 30% of cells after 1 week in culture and by an increased proportion at 2 and 3 weeks. The ability of a non-IgE-dependent stimulus, adenosine 5' triphosphate (ATP), to increase intracellular calcium in these cells was also tested. Calcium mobilization in large numbers of individual cells was monitored with use of a fluorimetric reagent and flow cytometry. Both antigen and ATP had significant effects on intracellular calcium in cells cultured for as little as 1 week with interleukin-3, when few cells exhibited morphologic or functional characteristics of mast cells. Longer times in culture were associated with an increase in the proportion of cells responding to these stimuli with calcium mobilization, but not with a change in the magnitude of the response. We conclude that the early expression of IgE receptors during mast cell development may be functionally significant, since these receptors appear to be linked to cellular signal transduction mechanisms. The data additionally imply a possible role for ATP in mast cell development.

Adenosine Triphosphate↗