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Biomedical subjects

D A Frank

Publications and source records attributed to D A Frank.

At least 73 records · Page 4Linked to original sources
PubMed1995

The thrombopoietin receptor c-MPL activates JAK2 and TYK2 tyrosine kinases.

Thrombopoietin (TPO) is a growth and differentiation factor for megakaryocyte-lineage cells. The receptor for TPO, c-MPL, is a member of the hematopoietic cytokine receptor family and has previously been shown to rapidly activate one or more cytoplasmic tyrosine kinases after ligand binding. In this study, we found that activation of the TPO receptor rapidly induced tyrosine phosphorylation of two members of the Jak tyrosine kinase family, JAK2 and TYK2, but not JAK1 or JAK3, in two different factor-dependent hematopoietic cell lines. The activation of both JAK2 and TYK2 was dose- and time-dependent and was associated with rapid tyrosine phosphorylation of a series of STAT proteins including STAT1, STAT3, and STAT5. Gel-shift assays indicated that one or more of these STATs is likely to participate in the formation of specific DNA-binding complexes. The activation of tyrosine kinases and signal propagation through tyrosine phosphorylation are likely to represent important initial steps in mediating the activities of TPO in myeloid cells.

Animals↗
PubMed1993

Characterization of a pathway for ciliary neurotrophic factor signaling to the nucleus.

Components of a signaling pathway that couples the ciliary neurotrophic factor (CNTF) receptor to induction of transcription were identified. CNTF stimulated the tyrosine phosphorylation of p91, a protein implicated in interferon signaling pathways, and of two proteins that are distinct but related to p91. Tyrosine-phosphorylated p91 translocated to the nucleus, where p91 and p91-related proteins bound to a DNA sequence found in promoters of genes responsive to CNTF. This DNA sequence, when inserted upstream of a reporter gene, conferred a transcriptional response to CNTF. A pathway that transduces interferon signals may therefore have a more general function in the propagation of responses to certain neurotrophic factors.

Base Sequence↗
PubMed1993

Resolution of an absolute scotoma and improvement of relative scotomata after successful macular hole surgery.

Visual loss in eyes with full-thickness macular holes is thought to be caused by the absence of retinal function in the area of the neurosensory defect as well as reduction in retinal function in the surrounding area of neurosensory retinal detachment. To improve characterization of the visual function of eyes after successful macular hole surgery, we studied six eyes preoperatively and postoperatively with macular microperimetry using the scanning laser ophthalmoscope. Best-corrected visual acuity was improved postoperatively in all eyes. Microperimetry performed preoperatively demonstrated an absolute scotoma that corresponded to the neurosensory defect in all eyes, with surrounding concentric isopters of relative scotomata. No detectable absolute scotoma was found in any eye postoperatively. All eyes showed partial or complete resolution of the surrounding relative scotomata. Improvements in visual acuity after successful macular hole surgery may be related to disappearance of a detectable absolute scotoma as well as improvement in the surrounding retinal function.

Aged↗
PubMed1993

Assessment of vision in idiopathic macular holes with macular microperimetry using the scanning laser ophthalmoscope.

BACKGROUND: Visual loss in eyes with full-thickness macular holes has been thought to be due to the absence of retinal function in the area of neurosensory defect as well as loss or reduction of retinal function in the surrounding area of neurosensory retinal detachment. With the advent of surgical techniques to treat macular holes, it is increasingly important to better characterize this visual dysfunction. METHODS: Thirty eyes of 30 patients with full-thickness idiopathic macular holes were evaluated with microperimetry using the scanning laser ophthalmoscope to detect and quantitate absolute and relative scotomata within the central 40 degrees of visual field. A log 2 scale of test stimulus intensities was established. Results of microperimetry were compared with best-corrected visual acuities as measured on the logarithmic Early Treatment of Diabetic Retinopathy Study chart as well as duration of symptoms. RESULTS: All 30 eyes showed an absolute scotoma in the area of neurosensory defect as well as surrounding relative scotomata in the area of neurosensory detachment. Best-corrected visual acuity was correlated with the size of the absolute and relative scotomata (P < 0.002). The sizes of the scotomata were correlated with the duration of symptoms of the macular holes (P < 0.05). CONCLUSION: Microperimetry using the scanning laser ophthalmoscope demonstrates that the visual loss associated with macular holes is related to the reduction of retinal function in the area of the surrounding neurosensory detachment as well as the absence of retinal function in the area of neurosensory defect. The size of the scotomata, determined by microperimetry, is correlated with the patient's visual acuity as well as the duration of symptoms of the macular hole.

Adult↗
PubMed1990

Neonatal body proportionality and body composition after in utero exposure to cocaine and marijuana.

The relationship of maternal use of marijuana and cocaine during pregnancy to measures of neonatal body proportionality and body composition was assessed in a multiethnic sample of 1082 newborn infants. Maternal use of marijuana and cocaine during pregnancy was ascertained by self-report and by an enzyme-multiplied immunoassay technique for screening of urine samples obtained prenatally and again post partum. After each substance was analytically controlled for use of the other and for other potentially confounding variables, detection of marijuana metabolites in maternal urine was associated (p less than 0.05) with depressed mean arm muscle circumference and nonfat area of the arm but not with any measure of neonatal fatness. In contrast, detection of cocaine in maternal urine was associated (p less than 0.05) with decrements of subscapular fat folds and of the fat and nonfat areas of the arm. Although both substances were associated with depressed birth weight, there was no decrement of neonatal ponderal index or of the arm circumference/head circumference ratio in association with exposure to either substance. We conclude that both marijuana exposure and cocaine exposure during pregnancy are associated with symmetric intrauterine growth retardation, but that deficits are in differing compartments of intrauterine growth. These findings suggest that marijuana may retard fetal growth through maternal-fetal hypoxia, whereas cocaine may alter nutrient transfer to the fetus and fetal metabolism.

Adipose Tissue↗
PubMed1989

Ecosystem-level patterns of primary productivity and herbivory in terrestrial habitats.

Ecosystems are structurally organized as food webs within which energy is transmitted between trophic levels and dissipated into the environment. Energy flow between two trophic levels is given by the amount of production at the lower level and by the proportion of production that is consumed, assimilated and respired at the higher level. Considerable evidence indicates that food-web structure varies predictably in different habitats, but much less is known about quantitative relationships among food web fluxes. Many of the energetic properties of herbivores in African game parks are associated with rainfall and, by inference, with net primary productivity. Respiratory costs per unit production at the consumer trophic level are higher for homeotherms than for heterotherms. Plant secondary chemicals affect herbivore dietary choices and the allocation of plant resources to those chemicals varies with resource availability. How these phenomena are translated into ecosystem fluxes is unknown. We present evidence that herbivore biomass, consumption and productivity are closely correlated with plant productivity, suggesting that the latter is a principal integrator and indicator of functional processes in food webs.

Animals↗
PubMed1989

Effects of maternal marijuana and cocaine use on fetal growth.

To investigate the effects on infants of the use of marijuana and cocaine during pregnancy and to compare the importance of urine assays with that of interviews in ascertaining drug use, we prospectively studied 1226 mothers, recruited from a general prenatal clinic, and their infants. On the basis of either interviews or urine assays conducted prenatally or post partum, 27 percent of the subjects had used marijuana during pregnancy and 18 percent had used cocaine. When only positive urine assays were considered, the corresponding values were 16 percent and 9 percent, respectively. When potentially confounding variables were controlled for in the analysis, the infants whose mothers had positive urine assays for marijuana, as compared with the infants whose mothers were negative according to both interviews and urine assays, had a 79-g decrease in birth weight (P = 0.04) and a 0.5-cm decrement in length (P = 0.02). Women who had positive assays for cocaine, as compared with nonusers, had infants with a 93-g decrease in birth weight (P = 0.07), a 0.7-cm decrement in length (P = 0.01), and a 0.43-cm-smaller head circumference (P = 0.01). To compare our findings with those of other investigators who did not use urine assays, we repeated the analyses, considering only self-reported use of marijuana (23 percent) and cocaine (13 percent). There were no significant associations between such use as determined by interviews alone and any of the measures of outcome. We conclude that the use of marijuana or cocaine during pregnancy is associated with impaired fetal growth and that measuring a biologic marker of such use is important to demonstrate the association.

Adolescent↗
PubMed1988

Biochemical characterization of tyrosine kinase and phosphotyrosine phosphatase activities of HL-60 leukemia cells.

The cellular phosphotyrosine content of the HL-60 promyelocytic leukemia markedly decreased during the induced granulocytic and monocytic maturation of these cells. This occurs in the face of major increases in tyrosine kinase and protein phosphotyrosine phosphatase activities (D. A. Frank and A. C. Sartorelli, Biochem. Biophys. Res. Commun., 140: 440-447, 1986). In the present work, these two activities were characterized in the particulate fraction of HL-60 cells, since both enzymes are membrane bound. The tyrosine kinase activity utilized ATP as a phosphate donor, although GTP and other nucleotides were competitive with ATP. The enzyme was temperature sensitive, had a pH optimum of 6.5, and required Mg2+ or Mn2+ for activity, with additional stimulation of activity being produced by Zn2+. Agents such as epidermal growth factor and insulin, which stimulate other tyrosine kinase enzymes, were without effect on the tyrosine kinase activity of HL-60 cells. Enzyme activity was stimulated, however, by non-ionic detergents and was inhibited by quercetin. The protein phosphotyrosine phosphatase activity was paralleled by that of p-nitrophenyl phosphatase, was inhibited by VO3-4, Zn2+ and F-, and was maximally active at a pH of 7 to 8. The characteristics of the tyrosine kinase and the protein phosphotyrosine phosphatase activities were distinct from those of other known proteins of these classes. Tyrosine kinase activity was predominantly located on the plasma membrane, while the protein phosphotyrosine phosphatase activity was concentrated on internal membranes. The activities of both enzymes present on the plasma membrane appeared to exist on the cytoplasmic face of this membrane. Further characterization of the activities of these enzyme systems and their contribution to the regulation of tyrosine phosphorylation would appear to be important to an understanding of the control of cellular proliferation and differentiation.

Adenosine Triphosphate↗
PubMed1988

Alterations in tyrosine phosphorylation during the granulocytic maturation of HL-60 leukemia cells.

Granulocytic maturation of HL-60 promyelocytic leukemia cells induced by dimethylsulfoxide has been shown to produce a decrease in cellular protein phosphotyrosine residues and increases in both tyrosine kinase and protein phosphotyrosine phosphatase activities (D. A. Frank and A. C. Sartorelli, Biochem. Biophys. Res. Commun., 140: 440-447, 1986). These changes have been shown to not be restricted to dimethylsulfoxide-induced differentiation, since similar changes occur in HL-60 cells initiated with retinoic acid and in HL-60 sublines resistant to dimethylsulfoxide-induced differentiation treated with the retinoid. These regulatory events are not directly coupled to growth arrest, which accompanies terminal maturation, since the anthracycline antibiotics aclacinomycin A and marcellomycin, which induce HL-60 differentiation, cause these changes in phosphotyrosine metabolism, while Adriamycin, at a level which produces an equivalent degree of growth inhibition but does not initiate the maturation of HL-60 cells, does not. Furthermore, an HL-60 subline deficient in hypoxanthine-guanine phosphoribosyltransferase, which differentiates in the presence of 6-thioguanine, produced a decrease in phosphotyrosine residues and increases in tyrosine kinase and phosphotyrosine phosphatase activities in response to the purine antimetabolite, while the parental HL-60 line, in which 6-thioguanine inhibits cellular proliferation but does not induce maturation, does not exhibit these changes. Finally, similar alterations in phosphotyrosine regulation were exhibited during anthracycline-induced differentiation of the murine myelomonocytic leukemia cell line WEHI-3B D+, supporting the concept that the phenomena measured represent a general response to inducers of the granulocytic differentiation of leukemia cells.

Aclarubicin↗
PubMed1988

Failure to thrive.

Malnutrition is the primary biologic insult in most cases of failure to thrive. A transactional model of infant development provides a framework for understanding the psychosocial context in which such malnutrition occurs. Each child who fails to thrive should receive a multidisciplinary evaluation to address the diagnostic and therapeutic implications of nutritional, medical, psychosocial, and developmental factors contributing to growth failure.

Child Development↗
PubMed1988

Elevated concentrations of 13,14-dihydro-15-keto-prostaglandin F-2 alpha in maternal plasma during prepartum luteolysis and parturition in dogs (Canis familiaris).

Concentrations of progesterone and of 13,14-dihydro-15-keto-prostaglandin F-2 alpha (PGFM) were measured in plasma collected from 6 bitches every 3 h starting 2.8-4.6 days before parturition (birth of first pup) and continuing until 0.4-0.8 days post partum, and in additional samples collected less frequently. Progesterone concentrations at 48, 24, 12 and 3 h pre partum averaged 2.8 +/- 0.3, 2.2 +/- 0.4, 1.0 +/- 0.3 and 0.7 +/- 0.2 ng/ml. At those times PGFM values averaged 380 +/- 80, 800 +/- 220, 1450 +/- 450 and 1930 +/- 580 pg/ml, respectively. Mean concentrations of PGFM increased about 2.5-fold between 48 and 15 h pre partum in association with the onset of luteolysis, and then increased another 2.5 times before parturition as progesterone fell to nadir values. Peak levels of PGFM ranged from 1060 to 7150 pg/ml (2100 +/- 600 pg/ml) and occurred within 1-9 h after the birth of the first pup and before the birth of the last pup. These results suggest that prepartum luteolysis in dogs is initiated by increases in maternal concentrations of PGF, and that progesterone withdrawal causes a further increase in PGF which completes luteolysis and provides a major portion of the uterotonic activity causing expulsion of pups.

Animals↗
PubMed1988

Cocaine use during pregnancy: prevalence and correlates.

Cocaine use during pregnancy was assessed by interviews and urine assays obtained prenatally and immediately postpartum from 679 urban women enrolled in prenatal care. Of these, 17% were found to have used cocaine at least once during pregnancy. Eight percent had urine assays positive for cocaine metabolites using the enzyme-mediated immunoassay technique with a cut-off of 300 ng/mL of benzoylecgonine. Of the cocaine users, 24% denied use at the time of the interview and were identified solely by urine assay. Cocaine users were significantly (P less than .01) less likely than nonusers to be married, Hispanic, or black born outside of the United States and were less well nourished. Users reported significantly (P less than .01) more sexually transmitted diseases, prior low birth weight infants, spontaneous and elective abortions, and greater use of alcohol, cigarettes, marijuana, opiates, and other illicit drugs during pregnancy. Because cocaine use is correlated with many potential risk factors, large sample sizes and multivariate statistical techniques are needed to determine whether cocaine use during pregnancy poses an independent risk for adverse neonatal outcomes.

Boston↗