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D E Fisher

Publications and source records attributed to D E Fisher.

At least 19 recordsLinked to original sources
PubMed1992

Myc/Max and other helix-loop-helix/leucine zipper proteins bend DNA toward the minor groove.

A distinct family of DNA-binding proteins is characterized by the presence of adjacent "basic," helix-loop-helix, and leucine zipper domains. Members of this family include the Myc oncoproteins, their binding partner Max, and the mammalian transcription factors USF, TFE3, and TFEB. Consistent with their homologous domains, these proteins bind to DNA containing the same core hexanucleotide sequence CACGTG. Analysis of the conformation of DNA in protein-DNA complexes has been undertaken with a circular permutation assay. Large mobility anomalies were detected for all basic/helix-loop-helix/leucine zipper proteins tested, suggesting that each protein induced a similar degree of bending. Phasing analysis revealed that basic/helix-loop-helix/leucine zipper proteins orient the DNA bend toward the minor groove. The presence of in-phase spacing between adjacent binding sites for this family of proteins in the immunoglobulin heavy-chain enhancer suggests the possible formation of an unusual triple-bended structure and may have implications for the activities of Myc.

Base Sequence↗
PubMed1991

TFEB has DNA-binding and oligomerization properties of a unique helix-loop-helix/leucine-zipper family.

The DNA-binding factor TFEB contains adjacent helix-loop-helix (HLH) and leucine zipper (LZ) domains flanked by an upstream basic region. This arrangement of interactive motifs has recently been observed in several other transcription factors and in the Myc family of oncogenes. TFEB was isolated by virtue of its binding to the major late promoter of adenovirus. DNA binding by a soluble protein was achieved by deleting a hydrophobic amino-terminal domain and permitted the structural analysis of the oligomerization and DNA-binding properties of TFEB. TFEB specifically bound DNA as both a homodimer and a heterodimer with another b-HLH-LZ protein TFE3. The LZ domain was essential for homo- or hetero-oligomerization and high-affinity DNA binding. In the absence of DNA a tetramer-sized form of TFEB was observed that dissociates to bind added DNA as a dimer. Binding by TFEB and TFE3 to related, but different, naturally occurring DNA target sequences was observed with distinct binding preferences. Analysis of basic domain residues in this family of proteins revealed a pattern of sequence conservation predictive of an interacting alpha-helical face. Common oligomerization and DNA-binding features suggest the b-HLH-LZ domain structure to define a distinct family of DNA-binding factors.

Adenoviridae↗
PubMed1991

Improved oxygenation with prone positioning in neonates: stability of increased transcutaneous PO2.

To evaluate the effect of body position on oxygenation and ventilation in neonates over a prolonged period, infants with respiratory disease were followed by transcutaneous (tc) monitoring for alterations in tcPO2 and tcPCO2 with position changes. In 14 studies of seven patients, prone positioning was compared with supine positioning over a 6-hour interval. All patients were premature, were receiving supplemental oxygen, and had respiratory disease secondary to prematurity. The median gestational age was 29 weeks; all infants were 2 months old or less at the time of the study. Prone positioning resulted in a significantly higher tcPO2; mean (+/- SD) tcPO2 increased from 63 (+/- 11.6) mm Hg to 71 (+/- 14.6) mm Hg, and decreased to 65 (+/- 11.2) mm Hg when the infant was returned to supine (P less than .05). This increase in tcPO2 was stable throughout 2 hours in the prone position. No significant change in tcPCO2 was detected. Infants were also found to spend a greater proportion of time sleeping when prone (75% +/- 13% vs 33% +/- 14%; P less than .05). These finding suggest that improvement in oxygenation with the prone position is stable over an extended period in the sick preterm infant.

Blood Gas Monitoring, Transcutaneous↗
PubMed1990

Percutaneous central venous catheterization. Three years' experience in a neonatal intensive care unit.

Prolonged venous access is desirable in very-low-birth-weight infants and infants for whom feedings are contraindicated. We prospectively evaluated 481 small-diameter venous catheters placed percutaneously in 317 patients over 3 years. Of 478 catheters, 241 (50%) were placed in infants weighing 1 kg or less. Mean catheter stay was 13 days (range, less than 1 to 77 days). Almost half (49%) of the central and thoracic catheters (91% of placements) were removed nonelectively: 43% due to problems such as leaking or clotting and 6% to suspicion of sepsis or venous occlusion. Of the 23 episodes of possible sepsis in the 478 catheter stays, six (1.3%) were confirmed catheter-related sepsis; 12 (2.5%) were confirmed alternate locus sepsis. Three factors specific to percutaneous central venous catheter-related sepsis were prolonged catheter stay (3 to 5 weeks), Staphylococcus epidermidis, and weight less than or equal to 1 kg. Four factors specific to alternate locus sepsis were presence of an alternate infection site, earlier infection (1 to 2 weeks), extremely low birth weight, and prolonged clinical instability. Percutaneous central venous catheterizations reduced the need for the stress of repeated venipuncture, resulting in lower complication rates than those reported with surgically placed central venous catheters, and leading to identification of risk factors specific to catheter sepsis and alternate locus sepsis.

Birth Weight↗
PubMed1990

A model for the prospective analysis of perinatal deaths in a perinatal network.

This prospective study assesses factors that contribute to perinatal mortality. The study population includes the 1362 perinatal deaths that occurred among 85,402 live births between 1983 and 1987 at hospitals of the University of Chicago Perinatal Network. After peer review of demographic, clinical, and pathologic data, each perinatal death was classified in one of the following categories: (1) the result of congenital malformation incompatible with life, (2) unavoidable, (3) potentially avoidable by patient, by health provider, or by both, or (4) of undetermined responsibility. Of 1362 deaths, 12.3% involved congenital malformations incompatible with life, 56.9% were classified as unavoidable, 28.1% were judged potentially avoidable, and 2.7% due to undetermined causes. Of potentially avoidable deaths, 36% were due to patient factors (primarily noncompliance), 59% to health provider factors, and 15% to combined patient and provider factors. There was a significant reduction in the potentially avoidable cases during the study period. The maximum attainable reduction in perinatal mortality under optimal conditions is calculated. Intervention plans to achieve this goal are discussed.

Chicago↗
PubMed1990

Assessment of potentially avoidable perinatal mortality in a regionalized program.

To obtain data regarding factors that influence perinatal mortality, a comprehensive perinatal mortality review project was prospectively developed and implemented. The resulting data cover a 21-month period and include all perinatal mortality at two perinatal centers and ten community hospitals. For each case an assessment of potential avoidability was made using the following definition: if any factor was identified that might have altered the outcome, the case was judged potentially avoidable. All other mortality was classified as either unavoidable or undetermined (if sufficient data were not available). During the review period there were a total of 26,937 live births and 591 cases of perinatal mortality. We conclude that: (1) meaningful analysis of factors affecting perinatal mortality data can be obtained by review of all deaths using a standardized classification; (2) in 21% of perinatal mortality at least one potentially avoidable factor could be identified that might have altered the outcome, while 74% was unavoidable and 5% undetermined; and (3) implementation of the review process enabled the reviewers to recognize patterns of potentially avoidable perinatal deaths.

Birth Weight↗
PubMed1989

Diffuse large cell lymphoma with discordant bone marrow histology. Clinical features and biological implications.

In patients with diffuse large cell lymphoma (LCL), bone marrow involvement at the time of diagnosis is a poor prognostic sign. Since 1980, the authors have encountered 13 patients LCL who had simultaneous bone marrow involvement by small cleaved cell lymphoma (11 cases) or mixed small and LCL (two cases), a phenomenon known as "discordant" or "divergent" bone marrow histology. The patients ranged in age from 33 to 85 years (median, 61 years) and presented most commonly with Stage III or IV disease, independent of bone marrow involvement. Seventy-seven percent achieved complete remission (CR) with combination chemotherapy; 50% of these eventually relapsed and died of their disease. One patient died of unrelated causes. No recurrences of low-grade lymphoma were observed, as judged either by clinical behavior or rebiopsy. The survival of the patients with discordant bone marrow histology was compared with that of patients with LCL with or without bone marrow involvement by LCL. Of the 11 patients with discordant marrow histology followed for a minimum of 2 years, four (36%) are long-term survivors; this is comparable to the 2-year survival of patients with LCL without bone marrow involvement (45%). In contrast, 89% of patients with bone marrow biopsy specimens positive for LCL died within 18 months from the time of diagnosis (mean survival, 5.7 months). All diffuse LCL tested were of B-lineage. The authors attempted to determine whether the presence of discordant bone marrow histologic types indicated an underlying low-grade B-cell lymphoma in these patients by evaluating the peripheral blood of the long-term survivors for the presence of clonal excess. Of the three surviving evaluable patients tested, one had evidence of clonal excess in the peripheral blood. For patients with LCL who have a simultaneous bone marrow biopsy positive for low-grade lymphoma (discordant marrow histology), survival is no different from that of patients with negative marrows, and markedly better than that for patients with marrows positive for diffuse LCL. The biological significance of discordant bone marrow histology is not clear at this time.

Adult↗
PubMed1989

Senior elective.

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Education, Medical, Undergraduate↗
PubMed1989

Placental transfer and fetal effects of maternal sodium beta-hydroxybutyrate infusion in the baboon.

We examined the effects of maternal sodium beta-hydroxybutyrate (NaBOHB) on the primate fetus to investigate the impact of ketosis not associated with acidosis on fetal metabolism. After a loading dose (600 mg/kg), NaBOHB was infused for 70 min (300 mg/kg.hr) into the maternal femoral vein of eight pregnant baboons, and placental transfer and fetal and maternal metabolic changes were observed during an acute experimental protocol. Maternal arterial levels rose from 0.70 +/- 0.21 to 5.42 +/- 0.93 mM (p less than 0.001), and fetal arterial levels from 0.34 +/- 0.09 to 2.76 +/- 0.64 mM (p less than 0.01). A maternal-fetal gradient of approximately 2:1 was observed in both baseline and steady-state infusion conditions and is similar to the human maternal-fetal ketone gradient. This is in contrast to the sheep where significantly higher gradients have been described. The elevated lactate, from 1.90 +/- 0.34 to 2.88 +/- 0.54 mM (p less than 0.05) and somewhat decreased pO2 values in the fetus from 54.8 +/- 8.9 to 45.0 +/- 3.8 mm Hg (p greater than 0.05 less than 0.1), without change in oxygen consumption (2.00 +/- 0.28 versus 1.73 +/- 0.15 mM/min) are features common to conditions of increased levels of fetal energy substrate. NaBOHB does not appear to contribute to oxidative energy metabolism of the whole fetus but may contribute to lipid stores. The significance of higher levels of BOHB in the primate fetus compared to the sheep fetus remains to be elucidated.

3-Hydroxybutyric Acid↗
PubMed1988

Precursors to glycogen in ovine fetuses.

Postprandial hepatic glycogenesis in the adult animal is now felt to proceed largely through gluconeogenic pathways rather than directly from glucose. The ovine fetus, like the mature sheep, lacks specific hepatic glucokinase. Therefore, we examined the role of lactate as a fetal glycogenic precursor in seven chronically catheterized 125-day sheep fetuses. Fetuses were infused with L-[U-14C]lactate and D-[3-3H]glucose (50 microCi load, 50 microCi/h for 5 h), while maternal glucose was maintained at 50 mg/dl. Mean fetal hepatic glycogen specific activity (microCi/mg x 10(3] was 0.82 +/- 0.08 for 14C and 2.6 +/- 0.4 for 3H, whereas fetal renal glycogen specific activity was 0.46 +/- 0.22 for 14C and 0.78 +/- 0.16 for 3H. In contrast, [14C]glucose specific activity was undetectable in blood (limit of detectability 1 microCi/mg x 10(3] and mean [3H]glucose specific activity was 8.9 +/- 1.3 microCi/mg x 10(3]. The least detectable specific activity of [14C]glucose did not differ significantly from the [14C]glycogen enrichment in liver, whereas [3H]glucose specific activity was significantly (P less than 0.02) greater than [3H]glycogen enrichment. We conclude that glycogenesis from glucose is partly through the indirect gluconeogenic route and that lactate may be a glycogenic precursor in the ovine fetus.

Animals↗
PubMed1987

The effect of initial Apgar score on the birthweight-specific survival of the very low-birthweight infant.

Gestational age (GA) and birthweight (BW) specific neonatal survival statistics were generated to examine the possible effect of one-minute Apgar score on outcome in very low birthweight (VLBW) infants. BW-specific and GA-specific survival is enhanced when the one-minute Apgar score is 4 or more. The route of delivery seems to matter little, although the cesarean section rate is higher for VLBW infants. The data suggest that preconceived notions about adverse outcome for this group of infants could be improved by delivery in better condition. Similarly, our approach for using BW- and GA-specific outcome, which includes condition at birth, can provide a more useful basis for comparing between different populations, allowing for some assessments to be made concerning the quality of care.

Apgar Score↗
PubMed1986

Gluconeogenesis from lactate in the chronically catheterized baboon fetus.

Gluconeogenesis from lactate may be qualitatively identified in the chronically catheterized baboon fetus in the maternal fed and fasted state. Infusion of 250 microCi U-14C-lactate to the fetus over a 150-min period leads to the appearance of 14C-glucose in the fetal circulation. Little 14C-lactate or glucose appears in the maternal circulation, supporting fetal production of glucose from lactate. Maternal glucose infusion seems to inhibit fetal gluconeogenesis. The mean plateau in percent disintegrations per minute of glucose compared to lactate in the maternal fed state is 14.7 +/- 2.2 compared to 16.1 +/- 3.0 in the maternal fasting state and 11.1 +/- 0.6 during maternal glucose infusion. It is clear that the primate fetus is capable of gluconeogenesis before term. Quantitation of this capacity awaits development of a model permitting assessment of maternal-placental and fetal substrate flux.

Animals↗
PubMed1985

Temporal shifts from Sm to ribonucleoprotein reactivity in systemic lupus erythematosus.

The Sm and RNP autoantibodies, found in the sera of many patients who have connective tissue diseases, recognize determinants on small nuclear ribonucleoprotein particles (snRNP). Numerous techniques have been used to distinguish between the subsets of snRNP proteins recognized by these two antibody systems. Using protein and snRNP immunoprecipitation, as well as a competitive enzyme-linked immunosorbent assay, antibodies in the sera of Sm patients have been observed to include variable quantities of RNP-like reactivity. To analyze changes in these autoantibodies, 2 patients with anti-Sm antibodies were followed temporally. The autoantibodies in the sera of both patients underwent shifts from predominant Sm reactivity to predominant RNP reactivity. In 1 patient the shift occurred gradually over several years, while in the other the shift occurred within 8 weeks.

Adult↗