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Biomedical subjects

M Sherman

Publications and source records attributed to M Sherman.

At least 109 records · Page 6Linked to original sources

Posttranscriptional stabilization of c-fms mRNA by a labile protein during human monocytic differentiation.

The c-fms proto-oncogene encodes a transmembrane glycoprotein that is closely related or identical to the receptor for the monocyte colony-stimulating factor CSF-1. The present studies examined the mechanisms responsible for the regulation of c-fms gene expression during human monocytic differentiation. Levels of c-fms mRNA were undetectable in HL-60 promyelocytic leukemia cells, while 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced monocytic differentiation of these cells was associated with the appearance of these transcripts. Run-on transcription assays demonstrated that the c-fms gene was transcriptionally active in uninduced HL-60 cells and that the rate of transcription was unchanged after TPA treatment. These findings suggested that c-fms mRNA levels in HL-60 cells are controlled by posttranscriptional mechanisms. The half-life of c-fms transcripts in TPA-induced HL-60 cells was found to be at least 6 h, while inhibition of protein synthesis with cycloheximide (CHX) decreased this half-life to 4 h. Moreover, inhibition of protein synthesis was associated with decreases in c-fms mRNA levels and a block in the induction of c-fms transcripts by TPA. These findings indicated that the c-fms transcript is stabilized by a labile protein. In contrast to HL-60 cells, c-fms mRNA is constitutively expressed in resting human monocytes and is down-regulated by treatment of these cells with TPA. Run-on assays demonstrated that TPA-induced downregulation of c-fms mRNA levels in monocytes occurred at the posttranscriptional level. Moreover, the results demonstrate that levels of c-fms mRNA are regulated posttranscriptionally by a labile protein. In this regard, the half-life of the c-fms transcript was 6.1 h in monocytes, while treatment of these cells with CHX decreased the half-life to 30 min. Furthermore, this effect of CHX occurred in the absence of changes in the rate of c-fms gene transcription. Together, these findings indicate that c-fms gene expression is regulated at a posttranscriptional level both in HL-60 cells induced to differentiate along the monocytic lineage and in human monocytes. The findings also indicate that levels of c-fms mRNA are regulated by the synthesis of a labile protein which is involved in stabilization of the c-fms transcript.

Cell Differentiation↗

Gonococcal arthritis case report.

In the case reported, the diagnosis of gonococcal arthritis unfolded over the course of 1 week and was not fully conclusive until presumptive therapy was initiated. Although the clinical, microbiologic, and immunologic characteristics of gonococcal arthritis can be differentiated from other types of bacterial arthritides, not all textbook symptoms are present at one time in one particular case. There also are subtle signs that are involved. In this case study, there was little definitive evidence that stood out to confirm the diagnosis. It was the interdependence of a complete history, serologic and radiographic studies, clinical presentation, and demographic considerations that led to an accurate diagnosis and timely treatment of gonococcal arthritis.

Adult↗

Downregulation of c-fms gene expression in human monocytes treated with phorbol esters and colony-stimulating factor 1.

The colony-stimulating factor-1 (CSF-1) regulates survival, growth, and differentiation of monocytes by binding to a single class of high-affinity receptors. The CSF-1 receptor is identical to the product of the c-fms protooncogene. The present studies monitored the effects of TPA and CSF-1 on c-fms gene expression in human monocytes. The results demonstrate that TPA downmodulates the constitutive expression of c-fms mRNA to low but detectable levels. Treatment of human monocytes with TPA was similarly associated with decreases in levels of the 138- and 125-Kd c-fms-encoded proteins. However, the kinetics of c-fms protein downmodulation indicated independent effects of TPA on c-fms expression at the RNA and protein levels. Furthermore, c-fms protein levels subsequently recovered despite persistently low levels of c-fms mRNA. Although previous studies demonstrated that c-fms protein is down-regulated in the presence of CSF-1, the present results indicate that CSF-1 also downregulates levels of c-fms mRNA. Moreover, the results indicate that CSF-1 increases protein kinase C activity in the membrane fraction. Together, these findings suggest that c-fms gene expression is differentially regulated at both the RNA and protein levels after activation of protein kinase C in human monocytes treated with TPA and CSF-1.

Blotting, Northern↗

Dose-dependent effects of epidermal growth factor on corneal wound healing.

The dose-dependent effect of epidermal growth factor (EGF) on the development of wound tensile strength following full-thickness corneal wounds was evaluated in 60 adult rabbits. One eye from each rabbit received a single 7-mm long corneal incision. After injury each rabbit was treated three times daily for 5 or 10 days with either EGF at 0.001 mg/ml (10 eyes), 0.01 mg/ml (10 eyes), 0.1 mg/ml (10 eyes), 1.0 mg/ml (15 eyes), or vehicle (15 eyes). The tensile strength of the wound was evaluated using a 5-mm wide strip of cornea mounted on a tensiometer. We found that EGF at 0.1 mg/ml and at 0.01 mg/ml increased wound strength by 100% at 5 days and by 60% at 10 days (P less than 0.05 and P less than 0.05). However, EGF at 0.001 mg/ml and 1.0 mg/ml appeared to have no effect on wound strength. Histologic examination of full-thickness wounds in a separate series showed an increase in wound fibroblastic response and a diminished fibrin clot at 5 days in rabbits treated with 0.1 mg/ml and 0.01 mg/ml. We conclude that EGF enhances the wound strength of full-thickness corneal wounds in a dose-dependent manner which may be explained in part by an increased fibroblastic response. Concentrations of EGF greater or less than an optimal dose may be less effective in enhancing corneal wound strength.

Administration, Topical↗

Atrial infarction: diagnosis and management.

Atrial infarction has been a relatively understudied entity. Its incidence by autopsy study has been widely variable, from 0.7% to 42%, with the largest series of 182 patients demonstrating an incidence of 17%. The right atrium is involved five times as often as the left, with the auricle the predominant site in either atria. Clinical atrial infarction may present with supraventricular arrhythmias, atrial rupture, hemodynamic compromise from loss of atrial "kick," and thromboembolic phenomena. Diagnosis currently is made in an appropriate clinical setting with characteristic PR interval changes. Other noninvasive techniques have shown only limited diagnostic utility, but esophageal echocardiography may prove to be a useful technique in this setting.

Arrhythmias, Cardiac↗

Self-ratings of graduating family practice residents' psychological medicine abilities.

This study evaluated the psychological medicine abilities of graduating residents in the Department of Family Practice and Community Health at the University of Minnesota Health Sciences Center (n = 41). Residents were asked to complete the Psychological Medicine Inventory, a series of nine-point rating scales, which measure level of interest in the psychological aspects of patient care, degree of confidence in dealing with the psychological problems of patients, and various psychological abilities. Behavioral science faculty members familiar with the residents also rated 20 of the residents' overall level of interest and ability in psychological medicine. Residents rated themselves highest on doctor-patient relationships and on recognizing patients in distress, and lowest on psychological interviewing and the ability to be psychologically therapeutic. Item intercorrelations and factor analysis suggested that two main dimensions were being evaluated: clinical psychological abilities (including interviewing, diagnosis, consultation, treatment decisions, and treatment) and psychological sensitivity (including doctor-patient relationships, awareness of patient's reactions, and awareness of own feelings.) Residents' self-ratings correlated positively with faculty ratings.

Clinical Competence↗

Respiratory muscle dysfunction in hereditary motor sensory neuropathy, type I.

Pulmonary function tests were performed on ten patients who were shown to have hereditary motor sensory neuropathy, type I. Mean values for spirometry, static lung volumes, and diffusion capacity were all greater than 80% of the predicted normal values for the group. In contrast, both inspiratory and expiratory muscle testing showed substantial reductions in function for the group. These abnormalities have not previously been reported, and they may be important in the management of these patients and in patients with other neuromuscular diseases.

Adolescent↗

Effects of ornithine decarboxylase inhibition on c-myc expression during murine erythroleukemia cell proliferation and differentiation.

The polyamines putrescine, spermidine, and spermine have been implicated in the regulation of cellular proliferation and differentiation. We have previously demonstrated that spermidine is required for proliferation of murine Friend erythroleukemia (MEL) cells. We have also shown that spermidine is required at a transcriptional level for induction of MEL globin synthesis. Since studies monitoring c-myc expression have suggested that this gene also plays a role in both growth and differentiation, we have monitored the effects of inhibiting ornithine decarboxylase (ODCase) activity and polyamine synthesis on levels of c-myc transcripts. The results demonstrate that the level of c-myc RNA is independent of ODCase inhibition and depletion of intracellular spermidine. More importantly, arrest of MEL proliferation is not associated with detectable changes in c-myc expression, while under these conditions there is a decline in ODCase transcripts. During induction of MEL differentiation with dimethyl sulfoxide (DMSO) and hexamethylene bisacetamide (HMBA), c-myc and ODCase undergo similar changes in patterns of expression. However, although spermidine is required for appearance of the differentiated MEL phenotype, depletion of this polyamine by ODCase inhibition had no detectable effect on the biphasic changes in c-myc RNA observed during MEL differentiation. Thus, these biphasic changes in c-myc expression are not sufficient for induction of the mature phenotype. Finally, these results would indicate that the regulation of c-myc expression during both proliferation and differentiation is independent of ODCase activity and inhibition of proliferation by spermidine depletion.

Acetamides↗

Pneumocystis carinii pneumonia with spontaneous pneumothorax. A report of three cases.

Spontaneous pneumothorax is a rare complication of pneumonia. Three cases of spontaneous pneumothorax in patients with Pneumocystis carinii pneumonia and acquired immunodeficiency syndrome are described. Two patients had bronchopleural fistulas. Local subpleural necrosis was felt to be the cause of the pneumothorax. Pneumothorax should be considered in patients with P carinii pneumonia who experience respiratory deterioration.

Acquired Immunodeficiency Syndrome↗

Deletion in chromosome 11p associated with a hepatitis B integration site in hepatocellular carcinoma.

Hepatitis B virus (HBV), a virus with known carcinogenic potential, integrates into cellular DNA during long-term persistent infection in man. Hepatocellular carcinomas isolated from viral carriers often contain clonally propagated viral DNA integrations. As small chromosomal deletions are associated with several types of carcinomas, the occurrence of chromosomal deletions in association with HBV integration in hepatocellular carcinoma was studied. HBV integration was accompanied by a deletion of at least 13.5 kilobases of cellular sequences in a human hepatocellular carcinoma. The viral DNA integration and deletion of cellular sequences occurred on the short arm of chromosome 11 at location 11p13-11p14. The cellular sequences that were deleted at the site of HBV integration were lost from the tumor cells, leaving only a single copy of the remaining cellular allele.

Animals↗

Vitamin A therapy in patients with Crohn's disease.

Vitamin A therapy has been claimed in isolated reports to be of benefit to patients with Crohn's disease. To investigate this further, 86 patients were entered into a long-term double-blind study of vitamin A, 50,000 U twice daily, as compared with placebo. After a mean of 14.1 mo of treatment there was no significant difference between the groups as measured by a variety of activity indices (including the National Cooperative Crohn's Disease Activity Index), the number of acute attacks, and the surgical rate. No toxic effects of vitamin A were observed during the study. In this study vitamin A has not been shown to be of benefit to patients with Crohn's disease who are in remission.

Adolescent↗

Thalassemic children's understanding of illness: a study of cognitive and emotional factors.

A study that explored children's understanding of the body and illness was conducted with 23 thalassemic outpatients and 27 healthy controls. The findings were supportive of a developmental progression in children's understanding that is reflective of their underlying cognitive maturity. Behavioral compliance was related to psychiatric adjustment. There was a trend toward poorer psychiatric adjustment in children with impaired understanding of their illness. These findings hold implications for both educational and psychiatric intervention with this group. Optimal health care of chronically ill children requires knowledge of the developmental course and interplay of children's cognition and their familial and personal adjustment.

Adaptation, Psychological↗

Ligandin concentrations in the steroidogenic tissues of the rat during development.

Ligandin, a ubiquitous multifunctional cytoplasmic protein which exhibits glutathione S-transferase, glutathione peroxidase and delta 5-3-ketosteroid isomerase activities and binds to cortisol metabolites, is present in relatively high concentrations in gonadal and adrenal tissue. In contrast to hepatic ligandin, little is known about the ontogeny of ligandin in steroid-synthesising tissues. We report here the intracellular concentrations of ligandin as well as the serum concentrations of testosterone and progesterone measured by radioimmunoassay at different stages of development in the rat. Ligandin levels in testis, ovary and adrenal tissue were relatively high soon after birth, decreased by day 9 and increased rapidly during puberty to reach adult levels. These changes appeared to be paralleled by changes in the circulating levels of testosterone and progesterone. In contrast, ligandin levels in non-steroidogenically active tissues, such as liver and kidney, were low at birth and rose progressively to reach adult levels. Whereas hepatic ligandin concentration could be increased at all stages of development by phenobarbital induction, no induction occurred in the endocrine tissues.

Adrenal Glands↗