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Biomedical subjects

M Levine

Publications and source records attributed to M Levine.

At least 109 records · Page 6Linked to original sources
PubMed1999

Criteria and recommendations for vitamin C intake.

Recommendations for vitamin C intake are under revision by the Food and Nutrition Board of the National Academy of Sciences. Since 1989 when the last recommended dietary allowance (RDA) of 60 mg was published, extensive biochemical, molecular, epidemiologic, and clinical data have become available. New recommendations can be based on the following 9 criteria: dietary availability, steady-state concentrations in plasma in relationship to dose, steady-state concentrations in tissues in relationship to dose, bioavailability, urine excretion, adverse effects, biochemical and molecular function in relationship to vitamin concentration, direct beneficial effects and epidemiologic observations in relationship to dose, and prevention of deficiency. We applied these criteria to the Food and Nutrition Board's new guidelines, the Dietary Reference Intakes, which include 4 reference values. The estimated average requirement (EAR) is the amount of nutrient estimated to meet the requirement of half the healthy individuals in a life-stage and gender group. Based on an EAR of 100 mg/d of vitamin C, the RDA is proposed to be 120 mg/d. If the EAR cannot be determined, an adequate intake (AI) amount is recommended instead of an RDA. The AI was estimated to be either 200 mg/d from 5 servings of fruits and vegetables or 100 mg/d of vitamin C to prevent deficiency with a margin of safety. The final classification, the tolerable upper intake level, is the highest daily level of nutrient intake that does not pose risk or adverse health effects to almost all individuals in the population. This amount is proposed to be less than 1 g of vitamin C daily. Physicians can tell patients that 5 servings of fruits and vegetables per day may be beneficial in preventing cancer and providing sufficient vitamin C intake for healthy people, and that 1 g or more of vitamin C may have adverse consequences in some people.

Antioxidants↗
PubMed1999

Local inhibition and long-range enhancement of Dpp signal transduction by Sog.

Extracellular gradients of signalling molecules can specify different thresholds of gene activity in development. A gradient of Decapentaplegic (Dpp) activity subdivides the dorsal ectoderm of the Drosophila embryo into amnioserosa and dorsal epidermis. The proteins Short gastrulation (Sog) and Tolloid (Tld) are required to shape this gradient. Sog has been proposed to form an inhibitory complex with either Dpp or the related ligand Screw, and is subsequently processed by the protease Tld. Paradoxically, Sog appears to be required for amnioserosa formation, which is specified by peak Dpp signalling activity. Here we show that the misexpression of sog using the even-skipped stripe-2 enhancer redistributes Dpp signalling in a mutant background in which dpp is expressed throughout the embryo. Dpp activity is diminished near the Sog stripe and peak Dpp signalling is detected far from this stripe. However, a tethered form of Sog suppresses local Dpp activity without augmenting Dpp activity at a distance, indicating that diffusion of Sog may be required for enhanced Dpp activity and consequent amnioserosa formation. The long-distance stimulation of Dpp activity by Sog requires Tld, whereas Sog-mediated inhibition of Dpp does not. The heterologous Dpp inhibitor Noggin inhibits Dpp signalling but fails to augment Dpp activity. These results suggest an unusual strategy for generating a gradient threshold of growth-factor activity, whereby Sog and its protease specify peak Dpp signalling far from a localized source of Sog.

Animals↗
PubMed1999

Groucho and dCtBP mediate separate pathways of transcriptional repression in the Drosophila embryo.

The precellular Drosophila embryo contains approximately 10 well characterized transcriptional repressors. At least half are short-range repressors that must bind within 100 bp of either upstream activators or the core transcription complex to inhibit (or quench) gene expression. The two long-range repressors can function over distances of 1 kilobase or more to silence transcription. Previous studies have shown that three of the five short-range repressors interact with a common corepressor protein, dCtBP. In contrast, the two long-range repressors, Hairy and Dorsal, recruit a different corepressor protein, Groucho. Hairy also was shown to interact with dCtBP, thereby raising the possibility that Groucho and dCtBP are components of a common corepressor complex. To investigate this issue, we have misexpressed wild-type and mutant forms of Hairy in transgenic embryos. Evidence is presented that Hairy-mediated repression depends on the Groucho interaction sequence (WRPW) but not the weak dCtBP motif (PLSLV) present in the native protein. Conversion of the PLSLV motif into an optimal dCtBP interaction sequence (PLDLS) disrupts the activity of an otherwise normal Hairy protein. These results suggest that dCtBP and Groucho mediate separate pathways of transcriptional repression and that the two proteins can inhibit one another when both bind the same repressor.

Alcohol Oxidoreductases↗
PubMed1999

Acute respiratory alkalosis associated with low minute ventilation in a patient with severe hypothyroidism.

PURPOSE: Patients with severe hypothyroidism present unique challenges to anesthesiologists and demonstrate much increased perioperative risks. Overall, they display increased sensitivity to anesthetics, higher incidence of perioperative cardiovascular morbidity, increased risks for postoperative ventilatory failure and other physiological derangements. The previously described physiological basis for the increased incidence of postoperative ventilatory failure in hypothyroid patients includes decreased central and peripheral ventilatory responses to hypercarbia and hypoxia, muscle weakness, depressed central respiratory drive, and resultant alveolar hypoventilation. These ventilatory failures are associated most frequently with severe hypoxia and carbon dioxide (CO2) retention. The purpose of this clinical report is to discuss an interesting and unique anesthetic presentation of a patient with severe hypothyroidism. CLINICAL FEATURES: We describe an unique presentation of ventilatory failure in a 58 yr old man with severe hypothyroidism. He had exceedingly low perioperative respiratory rate (3-4 bpm) and minute ventilation volume, and at the same time developed primary acute respiratory alkalosis and associated hypocarbia (P(ET)CO2 approximately 320-22 mmHg). CONCLUSION: Our patient's ventilatory failure was based on unacceptably low minute ventilation and respiratory rate that was unable to sustain adequate oxygenation. His profoundly lowered basal metabolic rate and decreased CO2 production, resulting probably from severe hypothyroidism, may have resulted in development of acute respiratory alkalosis in spite of concurrently diminished minute ventilation.

Acute Disease↗
PubMed1999

Ureteropyeloscopic diagnosis and treatment of upper urinary tract urothelial malignancies.

OBJECTIVES: To study the application of endoscopic techniques in treating upper urinary tract urothelial malignancies and to define subgroups that may benefit from these therapies. METHODS: During a 3-year period, 20 patients with upper urinary tract transitional cell carcinoma were referred specifically for endoscopic therapy. Indications for treatment included a solitary kidney, bilateral disease, modest renal insufficiency, and/or other significant comorbidities. All patients underwent retrograde ureteropyeloscopy. Lesions were biopsied, and lower grade tumors were treated with electrocautery or laser energy. High-grade lesions not amenable to minimally invasive techniques were palliated or treated with standard open surgery. Surveillance was performed at 3 to 4-month intervals by urine cytology and repeat panendoscopy on a similar schedule to lesions of the bladder treated endoscopically. RESULTS: Eleven patients (55%) were found to have low-grade, papillary transitional cell carcinoma of the upper urinary tract. Tumors ranged in size from less than 1 cm to filling the entire ureter. All papillary lesions were treated successfully using ureteroscopic techniques without any disease progression. Five small, low-grade recurrences (45%) were defined and treated endoscopically, with a mean follow-up of 17.3 months. Three patients were found at the time of initial diagnostic ureteroscopy to have higher grade lesions and endoscopic treatment was chosen in light of their severe comorbidities. On subsequent imaging, 2 of the 3 patients were suspected of having progression and underwent open surgery, both had carcinoma-in-situ only in the specimen. No tumor progression has been defined in this group to date, with mean follow-up of 16.3 months. A final third group of 6 patients were found to have nonpapillary, high-grade lesions at diagnostic endoscopy and underwent standard surgical resection. The disease of 4 of these 6 patients has progressed with metastases. CONCLUSIONS: Papillary, low-grade, low-stage tumors of the upper urinary tract are amenable to endoscopic resection irrespective of size and location. Patients with high-grade lesions defined endoscopically should be offered radical surgery in light of the high rate of disease progression.

Aged↗
PubMed1999

Concerns about allegations of child sexual abuse against teachers and the teaching environment.

OBJECTIVE: The major objective was to determine teachers' awareness of the potential for child abuse allegations against themselves and the effects on the teaching environment. METHOD: Of 3,000 questionnaires sent out to a random sample of New York state teachers, 515 were returned. The responding teachers were similar to New York state teachers in terms of gender, age, and racial/ethnic distribution. RESULTS: A large percent of the respondents (56%) were aware of false allegations made against a teacher in their school district. About a third (36.5%) expressed concern that a child abuse allegation could be made against them. In response to a vignette, forty-two (42%) advised a new teacher against being alone in a room with a student; 62% advised against casual touching; 70% advised against hugging or putting an arm around a student. Males more than female teachers, especially those teaching upper grades, advised against such contact. The more teachers expressed concern about abuse allegations against themselves, the more teachers advised against contact. CONCLUSIONS: Fear of abuse allegations are salient for teachers. Fears may cause teachers to limit contact with students with potentially adverse consequences for students and the teaching environment.

Adult↗
PubMed1999

Temporal expression patterns of 39 Brachyury-downstream genes associated with notochord formation in the Ciona intestinalis embryo.

Expression of the Brachyury (Ci-Bra) gene of the ascidian Ciona intestinalis is initiated at the 64-cell stage. Gene expression is restricted to notochord precursor cells, and Ci-Bra plays a key role in notochord differentiation. In a previous study, nearly 50 cDNA clones for potential Ci-Bra-downstream genes that are expressed in notochord cells were isolated. The present determination, by whole-mount in situ hybridization, of the temporal expression patterns of 19 notochord-specific and 20 notochord-predominant genes demonstrated that the timings of initiation of the expression of various genes was not identical. The expression of several genes was initiated as early as the gastrula stage. However, the expression of most of the notochord-specific genes commenced at the neural plate stage. Partial nucleotide sequence data of these clones suggest that genes expressed earlier encode potential transcriptional factors and/or nuclear proteins, while those expressed later encode proteins implicated in cell adhesion, signal transduction, regulation of the cytoskeleton, and components of the extracellular matrix. These gene activities may be associated with changes in cell shape and adhesion during the intercalation and extension of the notochord cells.

Animals↗
PubMed1999

A randomized controlled trial comparing plasma removal with white cell reduction to prevent reactions to platelets.

BACKGROUND: Recent data suggest that most reactions to platelets are caused by white cell (WBC)-derived cytokines that accumulate in the plasma portion of the component during storage. On the basis of this theory, the effectiveness of two interventions to prevent reactions, poststorage WBC reduction and plasma depletion, were compared. STUDY DESIGN: A multiple crossover design was used, in which platelet components for transfusion to a patient randomly were WBC reduced after storage, or the plasma supernatant was removed. Adults >17 years of age, with a hematologic disease requiring platelet transfusion support, were eligible for the study. Patients were assessed for signs and symptoms characteristic of a reaction during, immediately after, and 1 hour after transfusion. Reactions were graded as mild, moderate, or severe. Interleukin 6 levels were also measured in the transfused platelet components. RESULTS: There were 380 analyzable platelet transfusions to 30 patients. The frequency of reactions was 25.8 percent (48/186) in the transfusions of poststorage WBC-reduced platelets and 17.0 percent (33/194) in the transfusions of plasma-depleted platelets (p<0.008). The severity of the reaction was graded by the patient. Severe reactions occurred more frequently in connection with poststorage WBC-reduced platelets than with plasma-depleted platelets: 33.4 percent (16/48) versus 18.2 percent (6/33), respectively (p = 0.048). Regression analysis identified interleukin 6 as the most significant of the evaluated factors in its correlation with the risk of reaction. CONCLUSION: Plasma removal is more effective than poststorage WBC reduction in preventing reactions, especially severe reactions to platelets.

Adolescent↗
PubMed1999

Mastectomy or lumpectomy? Helping women make informed choices.

PURPOSE: To develop an instrument to help clinicians inform their patients about surgical treatment options for the treatment of breast cancer and to evaluate the impact of the instrument on the clinical encounter. METHODS: We developed an instrument, called the Decision Board, to present information regarding the benefits and risks of breast-conserving therapy (lumpectomy plus radiation therapy) and mastectomy to women with early-stage breast cancer to enable them to express a preference for the type of surgery. Seven surgeons from different communities in Ontario administered the instrument to women with newly diagnosed clinical stage I or II breast cancer over an 18-month period. Patients and surgeons were interviewed regarding acceptability of the instrument. The rates of breast-conserving surgery performed by surgeons before and after the introduction of the instrument were compared. RESULTS: The Decision Board was administered to 175 patients; 98% reported that the Decision Board was easy to understand, and 81% indicated that it helped them make a decision. The average score on a true/false test of comprehension was 11.8 of 14 (84%) (range, 6 to 14). Surgeons found the Decision Board to be helpful in presenting information to patients in 91% of consultations. The rate of breast-conserving surgery decreased when the Decision Board was introduced (88% v 73%, P =.001) CONCLUSION: The Decision Board is a simple method to improve communication and facilitate shared decision making. It was well accepted by patients and surgeons and easily applied in the community.

Adult↗
PubMed1999

Characterization of the transvection mediating region of the abdominal-B locus in Drosophila.

Genetic studies have identified an unusual transvection process in the Abdominal-B (Abd-B) locus of Drosophila. In some cases distal infraabdominal (iab) regulatory domains continue to activate the Abd-B promoter even when translocated onto different chromosomes. Transvection depends on an approx. 10 kb genomic DNA sequence, termed the transvection mediating region (tmr), located immediately downstream of the Abd-B transcription unit. Here we report a detailed analysis of this region. Different DNA fragments from the tmr were inserted into a variety of P-transformation vectors. Analyses of reporter gene expression in transgenic embryos and adults identify at least three cis-regulatory elements, including two enhancers (IAB7 and IAB8) and a new insulator DNA (Frontabdominal-8, Fab-8). Evidence is also presented for a Polycomb Response Element (PRE) linked to the IAB8 enhancer, and an internal promoter in the iab-8 domain, which transcribes the iab-7 and iab-8 cis-regulatory DNA, including the Fab-8 insulator. We discuss the significance of these findings with regard to Abd-B transvection and long-range enhancer-promoter interactions in mammalian globin loci.

ATP-Binding Cassette Transporters↗
PubMed1999

Regulation of Ci-tropomyosin-like, a Brachyury target gene in the ascidian, Ciona intestinalis.

Brachyury is a sequence-specific transcriptional activator that is essential for notochord differentiation in a variety of chordates. In vertebrates, Brachyury is expressed throughout the presumptive mesoderm, but becomes restricted to the notochord at later stages of development. In ascidians, such as Ciona intestinalis, Brachyury is expressed exclusively in the notochord and does not exhibit an early pan-mesodermal pattern. Subtractive hybridization screens were recently used to identify potential Ciona Brachyury (Ci-Bra) target genes (Takahashi, H., Hotta, K., Erives, A., Di Gregorio, A., Zeller, R. W., Levine, M. and Satoh, N. (1999). Genes Dev. 13, 1519-1523). Of the genes that were identified in this screen, one corresponds to a new member of the tropomyosin superfamily, Ciona tropomyosin (Ci-trop). Here we show that Ci-trop is specifically expressed in the developing notochord beginning at gastrulation, and expression persists in the notochord during tailbud and tadpole stages. A 3 kb region of the Ci-trop 5'-flanking sequence was characterized via electroporation of lacZ fusion genes into fertilized Ciona eggs. A minimal, 114 bp enhancer was identified that is sufficient to direct the expression of a heterologous promoter in the notochord. DNA binding assays indicate that this enhancer contains two sets of low-affinity Brachyury half-sites, which are bound in vitro by a GST/Ci-Bra fusion protein. Deletion of the distal sites inactivates the notochord-specific staining pattern mediated by an otherwise normal Ci-trop/lacZ transgene. These results suggest that Ci-trop is a direct target gene of Ci-Bra and that Brachyury plays an immediate role in the cellular morphogenesis of the notochord.

Amino Acid Sequence↗
PubMed1999

Interpreting meta-analyses of pharmacologic interventions: the pitfalls and how to identify them.

Meta-analyses are key components of evidence-based decision making. The numbers of meta-analyses published in different areas of health care increased dramatically during the past 10 years. Many of them covered different pharmacologic interventions, making them useful resources to clinical pharmacists. Although a well-conducted meta-analysis may be valuable, a poorly conducted one may have false conclusions and thus incorrectly alter a clinician's recommendations. Several key concepts must be considered when appraising meta-analyses of pharmacologic interventions.

Decision Making↗
PubMed1998

dCtBP mediates transcriptional repression by Knirps, Krüppel and Snail in the Drosophila embryo.

The pre-cellular Drosophila embryo contains 10 well characterized sequence-specific transcriptional repressors, which represent a broad spectrum of DNA-binding proteins. Previous studies have shown that two of the repressors, Hairy and Dorsal, recruit a common co-repressor protein, Groucho. Here we present evidence that three different repressors, Knirps, Krüppel and Snail, recruit a different co-repressor, dCtBP. Mutant embryos containing diminished levels of maternal dCtBP products exhibit both segmentation and dorsoventral patterning defects, which can be attributed to loss of Krüppel, Knirps and Snail activity. In contrast, the Dorsal and Hairy repressors retain at least some activity in dCtBP mutant embryos. dCtBP interacts with Krüppel, Knirps and Snail through a related sequence motif, PXDLSXK/H. This motif is essential for the repression activity of these proteins in transgenic embryos. We propose that dCtBP represents a major form of transcriptional repression in development, and that the Groucho and dCtBP co-repressors mediate separate pathways of repression.

Alcohol Oxidoreductases↗
PubMed1998

Suppressor of hairless activates brachyury expression in the Ciona embryo.

The Ciona Brachyury gene (Ci-Bra) is regulated, in part, by a 434-bp enhancer that mediates restricted expression in the notochord. Here we present evidence that a Ciona Suppressor of Hairless ¿Ci-Su(H)¿ protein functions as an activator of this enhancer. Point mutations that reduce the binding of a GST/Ci-Su(H) fusion protein in vitro diminish the expression of mutagenized Ci-Bra/lacZ transgenes in electroporated embryos. Overexpression of a Ci-Su(H) fusion protein containing the Drosophila Hairy repression domain interferes with notochord differentiation, producing mutant tadpoles with shortened tails. Expression of a constitutively activated Xotch receptor in the notochord, endoderm, and CNS also alters tail morphogenesis. These results suggest that a Notch-Su(H) pathway might participate in notochord differentiation in Ciona.

Amino Acid Sequence↗