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Biomedical subjects

A D Friedman

Publications and source records attributed to A D Friedman.

At least 19 recordsLinked to original sources
PubMed1992

A novel temporal expression pattern of three C/EBP family members in differentiating myelomonocytic cells.

Members of the CCAAT/enhancer binding protein (C/EBP) family have been shown to regulate the terminal differentiation of adipocytes and hepatocytes. In these cell lineages, high levels of C/EBP alpha are found only in mature, nondividing cells. Using Western blotting and immunohistochemical staining, we have determined the temporal order of expression for C/EBP alpha, C/EBP beta, and C/EBP delta in differentiating myelomonocytic marrow cells. These studies show a unique temporal pattern of C/EBP isoform expression in the myeloid lineage. In particular, C/EBP alpha expression is very high in proliferative myelomonocytic cells, and diminishes during phenotypic maturation. While we have detected C/EBP alpha, C/EBP beta, and C/EBP delta in multiple myeloid leukemia cell lines, and C/EBP alpha in normal myeloid cells and in de novo human myeloid leukemias, we have not detected these C/EBP isoforms in either erythroid or lymphoid cells. Finally, we show that C/EBP alpha, C/EBP beta, and C/EBP delta protein and messenger RNA levels correlate in maturing granulocytic cells. The formation of tissue-specific combinations of C/EBP homodimers and heterodimers may allow this family of transcription factors to regulate different sets of genes in adipocytes, hepatocytes, and myelomonocytes.

Antigens, Surface↗
PubMed1992

Superficial fungal infections of the skin. Diagnosis and current treatment recommendations.

Superficial fungal infections are common. Most diagnoses of fungal infections of the skin can be made by physical examination, assisted by the use of a Wood's lamp, skin scrapings for microscopic examination, and fungal cultures. Dermatophyte infections are common at all ages, in both sexes, and they have a worldwide distribution. These infections include tinea capitis, tinea cruris, tinea pedis, tinea corporis, tinea manuum and tinea barbae. Tinea versicolor, caused by Malassezia furfur, and candidal infections are also common. Treatment modalities include oral and topical agents. Good personal hygiene is an important adjunct to antifungal therapy. Decisions regarding the appropriateness of therapy in a given patient must take into account the extent and location of the infection, the benefits and risks of each of the treatments, and cost. Oral therapies include griseofulvin, ketoconazole, and itraconazole. There are a large variety of topical treatments, including nystatin, selenium sulfide, tolnaftate, haloprogin, miconazole, clotrimazole, and sodium thiosulfate. Important to successful treatment is compliance with what is sometimes a long course of treatment, and good personal hygiene.

Administration, Topical↗
PubMed1991

Transcriptional regulation of two myeloid-specific genes, myeloperoxidase and lactoferrin, during differentiation of the murine cell line 32D C13.

The transcriptional regulation of myeloperoxidase (MPO) and lactoferrin (LF) was examined during terminal myeloid differentiation of the murine cell line 32D C13. The rates of transcription initiation for MPO and LF, determined by an in vitro nuclear run-on assay, increased approximately ninefold. The accumulation of MPO mRNA in 32D C13 cells, determined by Northern blot analysis, correlated temporally with the observed increase in MPO transcription initiation. On the other hand, accumulation of LF mRNA lagged behind the observed increase in LF transcription initiation. In mouse L cells, the LF gene was transcribed more frequently than the MPO gene, though neither mRNA accumulated. Finally, murine MPO transcription is shown, by Northern blot and primer extension analysis, to initiate at multiple sites. These results indicate that whereas transcription induction may largely account for the accumulation of MPO mRNA during terminal myeloid differentiation, both transcriptional and posttranscriptional mechanisms operate to allow accumulation of LF mRNA. The 32D C13 cell system will be a useful model for elucidating these mechanisms.

Animals↗
PubMed1991

CCAAT-enhancer binding protein: a component of a differentiation switch.

The CCAAT-enhancer binding protein (C/EBP) has now been found to promote the terminal differentiation of adipocytes. During the normal course of adipogenesis, C/EBP expression is restricted to a terminal phase wherein proliferative growth is arrested, and specialized cell phenotype is first manifested. A conditional form of C/EBP was developed, making it feasible to test its capacity to regulate the differentiation of cultured adipocytes. Premature expression of C/EBP in adipoblasts caused a direct cessation of mitotic growth. Moreover, when abetted by the effects of three adipogenic hormones, C/EBP promoted terminal cell differentiation. Since C/EBP is expressed in a variety of tissues, it may have a fundamental role in regulating the balance between cell growth and differentiation in higher animals.

Adipose Tissue↗
PubMed1991

Pancreatic enlargement in alcoholic pancreatitis: prevalence and natural history.

We determined the prevalence and natural history of pancreatic enlargement by abdominal ultrasonography or computed tomography in 72 patients with alcoholic pancreatitis. Pancreatic enlargement was observed in 54 patients (75%); it was diffuse in 28 (52%) and focal in 26 (48%). The focal enlargement was frequently cystic (50%), while the diffuse enlargement was only occasionally cystic (7%). Sequential imaging of the pancreas in 29 patients demonstrated partial to total resolution of pancreatic enlargement in greater than 50% during 6 months of follow-up. Determination of serum amylase and p-isoamylase activity was neither sensitive nor specific for pancreatic enlargement in alcoholic pancreatitis.

Acute Disease↗
PubMed1990

Long term radiologic outcome of Pseudomonas osteomyelitis of the foot.

The medical records of 27 patients with puncture wound-induced Pseudomonas aeruginosa osteomyelitis/septic arthritis of the foot hospitalized from 1980 through 1988 were reviewed. Twenty patients received anti-Pseudomonas therapy for greater than 21 days and 7 patients received anti-Pseudomonas therapy for less than or equal to 21 days. There was no difference in age, sex, race, duration of wound or symptoms before admission or in admission physical findings including temperature, lymphadenopathy, puncture site appearance or admission laboratory data including white blood cell count or erythrocyte sedimentation rate between the two groups. All children but two in the long term therapy group had surgical as well as parenteral anti-Pseudomonas therapy. Fifteen patients returned for follow-up radiographs 1 to 8 1/2 years after hospitalization, 10 of 20 who had received therapy for greater than 21 days and 5 of 7 who had received therapy for less than or equal to 21 days. Poor radiologic outcome, ranging from bony deformity to joint space abnormality, was noted in 4 patients, of whom 3 had had joint involvement. Clinical abnormality was noted in only one adolescent male, and he had the most severe radiologic sequelae. The longer term functional significance of these radiologic anomalies awaits further delineation.

Adolescent↗
PubMed1990

Impetigo therapy.

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Anti-Bacterial Agents↗
PubMed1990

Efficacy of sponging vs acetaminophen for reduction of fever. Sponging Study Group.

Seventy-three children with acute febrile illnesses were enrolled in a study to compare the efficacy of sponging, sponging plus acetaminophen, and acetaminophen alone as methods of lowering body temperature. The greatest temperature reduction was seen in the combined acetaminophen plus sponging group. The smallest temperature reduction was noted in children who received sponging alone. We urge reconsideration of routine sponging of febrile young patients.

Acetaminophen↗
PubMed1990

Identification of two polypeptide segments of CCAAT/enhancer-binding protein required for transcriptional activation of the serum albumin gene.

We used molecular genetic methods to generate systematically altered forms of CCAAT/enhancer-binding protein (C/EBP). The aim of our experiments was to identify regions of C/EBP that contribute to its capacity to activate transcription from the promoter of the serum albumin gene in cultured hepatoma cells. Earlier experiments had shown that the DNA-binding domain must remain intact for C/EBP to activate albumin transcription. We now provide evidence of two additional elements of C/EBP that are required for its gene-activating role. One such element occurs within a 28-residue region located close to the amino terminus of the protein. The other maps to a broader, more internal region of the protein and appears to exhibit functional redundancy. These newly defined elements of C/EBP exhibit two characteristics of "activation" domains delineated in studies of other gene regulatory proteins. First, they play no obvious role in the capacity of C/EBP to bind to its DNA substrate. Second, they retain function after being appended onto the DNA-binding domain of a different protein. Neither of these putative activating elements is characterized by overt distinction in either charge or preponderance of any particular amino acid. The more amino-terminal element does, however, exhibit several features suggesting that it may assume an alpha-helical structure. These studies offer observations and reagents that will be valuable for future studies concerning the physiologic function of C/EBP.

Amino Acid Sequence↗
PubMed1989

CCAAT/enhancer binding protein activates the promoter of the serum albumin gene in cultured hepatoma cells.

An expression vector capable of encoding full-length CCAAT/enhancer-binding protein (C/EBP) has been constructed and tested in transient transfection assays for its capacity to activate transcription from the promoter of the serum albumin gene. When tested in cultured hepatoma cells, the C/EBP expression vector achieved potent trans-activation of the albumin promoter. Less substantial activation was observed when the same experiment was conducted using cultured mouse fibroblasts. Expression vectors that encoded defective forms of C/EBP failed to activate the albumin promoter. Moreover, mutated variants of the albumin promoter that lack the C/EBP-binding site failed to be trans-activated. The data are consistent with the interpretation that C/EBP is a bona fide transcription factor. During the course of these experiments it was noted also that C/EBP is more than an order of magnitude less concentrated in cultured hepatoma cells than it is in adult liver cells. Given these findings, we speculate that C/EBP may play a general role in establishing and maintaining the differentiated, nonproliferative state.

Animals↗
PubMed1989

Differentiation-induced gene expression in 3T3-L1 preadipocytes: CCAAT/enhancer binding protein interacts with and activates the promoters of two adipocyte-specific genes.

Previous studies have shown that differentiation of 3T3-L1 preadipocytes leads to the transcriptional activation of a group of adipose-specific genes. As an approach to defining the mechanism responsible for activating the expression of these genes, we investigated the binding of nuclear factors to the promoters of two differentiation-induced genes, the 422(aP2) and stearoyl-CoA desaturase 1 (SCD1) genes. DNase I footprinting and gel retardation analysis identified two binding regions within the promoters of each gene that interact with nuclear factors present in differentiated 3T3-L1 adipocytes. One differentiation-induced nuclear factor interacts specifically with a single binding site in the promoter of each gene. Competition experiments showed that the interaction of this nuclear factor with the SCD1 promoter was prevented specifically by a synthetic oligonucleotide corresponding to the site footprinted in the 422(aP2) promoter. Several lines of evidence indicate that the differentiation-induced nuclear factor is CCAAT/enhancer binding protein (C/EBP), a DNA-binding protein first isolated from rat liver. Bacterially expressed recombinant C/EBP binds to the same site at which the differentiation-specific nuclear factor interacts within the promoter of each gene. Northern analysis with RNA from 3T3-L1 cells shows that C/EBP mRNA abundance increases markedly during differentiation. Transient cotransfection studies using a C/EBP expression vector demonstrate that C/EBP can function as a trans-activator of both the 422(aP2) and SCD1 gene promoters.

Adipose Tissue↗