Evidence that human cardiac myocytes divide after myocardial infarction.
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Biomedical subjects
Publications and source records attributed to J Wurzel.
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Extramedullary hematopoiesis occurring in the myocardium has previously only been reported in a single case of a neonate with cyanotic congenital heart disease. Herein we report the incidental discovery of extramedullary hematopoiesis or pure erythropoiesis in four failing adult hearts with myocardial infarction. In two cases, extramedullary hematopoiesis or erythropoiesis was identified in cardiectomy specimens removed at orthotopic heart transplantation; in two other cases, erythropoiesis was found in left ventricular tissue removed at the time of implantation of left ventricular assist devices. Myocardial hematopoiesis/erythropoiesis was identified based on characteristic light-microscopic findings in routinely processed tissue and was confirmed by immunhistochemistry using monoclonal antibodies to the erythroid cell marker glycophorin A (positive in all cases), the megakaryocyte marker CD61, and the granulocyte marker neutrophil elastase (the latter two markers positive in one case only). None of the four patients had a myeloproliferative disorder or evidence of a myelophthisic process. No hematopoietic elements were identified in 109 cardiectomy specimens without acute or recent infarcts. Myocardial hematopoiesis or erythropoiesis could represent heretofore-unrecognized manifestations of altered cytokine expression in patients with heart failure due to myocardial infarction.
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OBJECTIVE: The study was designed to evaluate the effectiveness of digital photography for dermatologic diagnoses and compare it with in-person diagnoses. MATERIALS AND METHODS: Patients referred for specialty consultations (n = 308) were recruited from a university dermatology clinic. Patients were examined in-person by one of three board-certified dermatologists who provided clinical diagnoses. Digital photos were obtained on all patients and were evaluated as computer images by a panel of dermatologists. RESULTS: There was 83% concordance between in-person versus digital photo diagnoses. Intradermatologist concordance averaged 84%, and interdermatologist concordance averaged 81%. Decision confidence was rated as "very definite" to "definite" 62% of the time. Concordance with biopsy results was achieved in 76% of the cases. Image sharpness and color quality were rated "good" to "excellent" 83% and 93% of the time, respectively. CONCLUSION: Digital photography for store-and-forward teledermatology produces high-quality images and diagnostic concordance rates that compare favorably with in-person clinical diagnoses.
Peptide growth factors likely play an important role in cardiac development, but growth factors which inhibit or prevent differentiation in cardiac myocytes are largely unknown. Using immunocytochemistry, Western and Northern blotting, and RNase protection assays, we demonstrate that epidermal growth factor (EGF) significantly inhibits differentiation and promotes proliferation in cultured human fetal ventricular cardiac myocyte cell lines. In enriched cell lines and in a pure myocyte cell strain, EGF inhibited increases in immunoreactive sarcomeric actin and sarcomeric myosin heavy chain (SMHC) normally seen after serum withdrawal. In the pure myocyte strain, EGF induced a cardiomyoblastic phenotype; i.e., it caused a complete loss of detectable sarcomeric proteins in the majority of cells; it was also mitogenic. EGF inhibited expression of cardiac alpha-actin and SMHC mRNAs, but inhibition of SMHC expression was predominantly of the beta-MHC isoform. Removal of EGF was followed by reexpression of sarcomeric proteins. Blocking the EGF receptor (EGFR) with monoclonal anti-receptor antibody completely abolished the dedifferentiating effects of EGF and also significantly reduced the mitogenic effect of the peptide. The results indicate that activation of the EGFR both inhibits differentiation and promotes proliferation of human fetal ventricular myocytes in vitro. These findings suggest an important role for EGF in human cardiac differentiation and development.
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Challenged by annual expenditures exceeding $5.9 million dollars for specialty support surface rentals, the National Center for Cost Containment (NCCC), an office of the Department of Veterans Affairs (VA), organized a Technical Advisory Group (TAG) to identify strategies for the appropriate use and cost-containment of specialty support surfaces. A survey of utilization patterns revealed that some VA facilities (n = 20) had no expenditures for rental of specialty support surfaces while others (n = 13) spent over $100,000 per facility on rental expenditures. Many facilities had a significant cost savings by owning specialty support surfaces. A decision-making tree, emphasizing first line devices, was developed to assist in containing expenditures. It was recommended that this algorithm be used in conjunction with the Specialty Support Surface Guidelines developed by the TAG. It is anticipated that this information may assist both VA and non-VA healthcare facilities to contain costs in the utilization of specialty support surfaces.
Previous work has suggested that subcultivated human fetal heart muscle cell cultures contain immature cardiac muscle cells capable only of limited differentiation after mitogen withdrawal. We studied several human fetal heart cultures (14-15 wk gestation) at several passage levels using immunocytochemistry, autoradiography, and Northern blot analysis. Characteristics in high-mitogen (growth) medium were compared with those after serum withdrawal. Cultured cells from one heart, expanded through 2 passages in growth medium, did not beat; however, 75% of cells did beat after subsequent culture for 24 days in low-serum (differentiation) medium containing insulin. In confluent cultures after 1 passage, there was no detectable difference in the number of cardiac myocytes present in growth medium compared with that 7 days after serum withdrawal. After 4 passages, however, serum withdrawal increased the number of cells expressing immunoreactive sarcomeric myosin heavy chain by 100-fold; expression of immunoreactive sarcomeric actin and alpha-cardiac actin mRNA also increased in the same cultures. Similar results were obtained in cultures kept in differentiation medium for 20 days before passage and expansion in growth medium. Using isopycnic centrifugation, a high-density cell fraction was isolated which contained no immunostained myocytes in growth medium but numerous myocytes after serum withdrawal. Combined immunocytochemistry/autoradiography showed that myocytes synthesize DNA in growth medium and in serum-free medium containing fibroblast growth factor, but not in serum-free medium alone. The results indicate that a) human fetal cardiac muscle cells proliferate in vitro and can maintain a phenotype characteristic of fetal myocytes after multiple subcultivations followed by serum withdrawal; b) after subcultivation in growth medium, some myocytes modulate their phenotype into one in which detectable levels of cardiac contractile proteins are expressed only after mitogen withdrawal, and c) the phenotype attained after serum withdrawal is in part dependent on passage level. Cultured human fetal myocardial cells may provide a useful experimental system for the study of human cardiac muscle cell biology.
The human adenine nucleotide translocator multigene family consists of three transcribed genes and at least seven pseudogenes. We report the cloning and sequencing of the gene expressed in human fibroblasts. Like the other two transcribed genes, it has four exons. The 5'-flanking region of the fibroblast translocase gene contains a functional promoter. The promoter has a TATA motif beginning 30 base pairs upstream of the transcription initiation site and five potential SP1 binding sites, but lacks a canonical CCAAT box immediately upstream of the TATA sequence. Differences among the sequence motifs of the 5'-flanking region of the three human translocase genes could account for differences in their cell type-specific and proliferation-associated expression.
There are at least three transcriptionally active human ADP/ATP translocase genes. We have isolated seven ADP/ATP translocase pseudogenes from recombinant human genomic libraries. Each pseudogene sequence had more than 85% identity with the sequence of the human ADP/ATP translocase cDNA derived from fibroblast mRNA, but each had mutations that precluded synthesis of a functional protein. Using an intron probe derived from a partial clone of the human fibroblast ADP/ATP translocase gene, we localized the gene to chromosome Xq13----Xq25-26. The gene encoding the skeletal muscle translocase has previously been shown to be on chromosome 4. Therefore, the human ADP/ATP translocase genes are members of a multigene family that includes pseudogenes and has been dispersed to at least two chromosomes.
A rare tumor, primary choriocarcinoma of the stomach, occurred in a post menopausal female. The diagnosis was confirmed by autopsy and by immunohistochemical demonstration of HCG in trophoblastic tumor cells. Theories concerning development of this neoplasm are briefly discussed. In addition, this postmenopausal case uniquely permitted examination of the hormonal effects of the tumor on target tissues without the clouding issue of normal menstrual hormones. It appears that the observed estrogen- and progesterone-related tissue responses were not mediated through the ovary; instead, direct tumor production of these hormones is implicated.
Among previously untreated cases of invasive carcinoma of the cervix in intact uterus evaluated and treated at the authors' institution, primary adenocarcinoma accounted for 20% of the entire group. This incidence is higher than in previously reported series. It is felt that while the true frequency of this entity is increasing, careful fractional curettage, attention to morphologic characteristics, and special stains will distinguish adenocarcinoma from primary endometrial adenocarcinoma. Eight of 10 patients with Stage I adenocarcinoma were found to have sterilized hysterectomy specimens after preoperative irradiation. Radiation therapy alone may be adequate for Stage I adenocarcinoma.
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OBJECTIVE: To determine the effects of radiant heat applied through a semiocclusive dressing on periwound skin temperature and wound healing. DESIGN: Before-after trial. SETTING: Spinal cord injury and geriatric units of a VA medical center. PATIENTS: Twenty inpatients with 21 Stage III and IV pressure ulcers. INTERVENTIONS: A semiocclusive, heated dressing was applied to 15 Stage III and IV pressure ulcers for 4.5 hours, Monday through Friday, for 4 consecutive weeks. The dressing emitted heat at 38.0 degrees C for 2 60-minute periods daily. At all other times, the wounds received only standard wound care. Six wounds in a separate control group received only standard wound care during the same 4-week period. MAIN OUTCOME MEASURES: Periwound skin temperature within and adjacent to the dressing and measurements of wound surface area. MAIN RESULTS: Mean skin temperatures inside and outside the heated dressing increased by 0.97 degree C and 1.08 degrees C (P < .05), respectively, from baseline values. Wounds treated with standard care plus the heated dressing underwent a statistically significant reduction in mean surface area of 60.73%. Wounds in the control group underwent a statistically insignificant reduction in mean surface area of 19.24%. CONCLUSION: Wounds treated with a radiant heat dressing healed significantly faster than wounds that received only standard care. There were no adverse effects from the radiant heat dressing.