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Biomedical subjects

A Levine

Publications and source records attributed to A Levine.

At least 55 records · Page 3Linked to original sources
PubMed1999

Celiac disease associated with familial chronic urticaria and thyroid autoimmunity in a child.

An 11-year-old girl presented with chronic urticaria (CU), antithyroid antibodies, and anemia. Celiac disease was diagnosed. The family history was positive for maternally derived CU and thyroid autoimmunity in three generations. Human leukocyte antigen typing disclosed human leukocyte antigen DQA1*0501 DQB1*0201 in both mother and child. CU was unresponsive to a gluten-free diet despite clinical and laboratory resolution of celiac disease in contrast to previous reports in adults. We believe that this is the first report of this association in a child, highlighting that CU may be a part of the spectrum of autoimmune phenomenon related to celiac disease.

Autoantibodies↗
PubMed1999

Treatment of therapy-refractory B-lineage acute lymphoblastic leukemia with an apoptosis-inducing CD19-directed tyrosine kinase inhibitor.

Seven children and eight adults with CD19+ B-lineage acute lymphoblastic leukemia, as well as one adult with chronic lymphocytic leukemia, were treated with the CD19 receptor-directed tyrosine kinase inhibitor B43-Genistein. All patients had failed previous chemotherapy regimens, and six patients had relapsed after bone marrow transplantation. B43-Genistein was administered as a 1-hour i.v. infusion at 0.1-0.32 mg/kg/day dose levels for 10 consecutive days or 3 consecutive days weekly for a total of nine doses. B43-Genistein was well tolerated by all patients with no life-threatening side effects. There were six episodes of grade 2-3 fever, two of which were clearly drug related, one episode each of grade 3 myalgia, grade 2 sinus tachycardia, and grade 2 vascular leak syndrome. There was one durable complete remission and two transient responses. Pharmacokinetic analyses in 12 patients revealed a plasma half-life of 20 +/- 5 h, mean residence time of 24 +/- 5 h, and a systemic clearance rate of 20 +/- 3 ml/h/kg. Moderate levels of human antimouse antibody (HAMA) ranging from 20-87 ng/ml were detected in the day 28 blood samples from three of nine cases examined. Treatment of these three HAMA-positive patients with a second course of B43-Genistein did not yield measurable immunoconjugate levels in the plasma, indicating that the administered B43-Genistein molecules were rapidly cleared from circulation due to the HAMA. On the basis of its acceptable toxicity profile and its ability to elicit objective responses at nontoxic dose levels, B43-Genistein may provide the basis for an effective treatment strategy for B-lineage acute lymphoblastic leukemia patients who have failed standard therapy.

Adolescent↗
PubMed1998

Seroprevalence of HTLV-I and HTLV-II among a cohort of HIV-infected women and women at risk for HIV infection. Women's Interagency HIV Study.

OBJECTIVES: To determine the seroprevalence of, and risk factors for, HTLV-I and HTLV-II infection among HIV-infected women and women at high risk for HIV infection. DESIGN: Cross-sectional analysis of baseline data for women enrolled in the prospective Women's Interagency HIV Study (WIHS). METHODS: From October 1994 through November 1995, 2657 women from five metropolitan areas in the United States (Chicago, Los Angeles, New York City [two sites], Northern California, and Washington DC) were enrolled in WIHS. An interview-based survey collected data on demographics, behavior, and medical history. HTLV-I and HTLV-II determinations were made using a combined HTLV-I/HTLV-II indirect immunofluorescent antibody (IFA) screening test, an IFA titration specificity test, and individual HTLV-I and HTLV-II confirmatory Western blots. Fisher's exact tests and logistic regression were used to determine univariate and multivariate independent predictors for HTLV-II infection. RESULTS: Of 2625 women enrolled in WIHS with confirmed HIV results, 2487 (95%) were tested for HTLV-I and HTLV-II. Of these, 241 (10%) were HTLV-II-seropositive and 13 (0.5%) were HTLV-I-seropositive. On multivariate analysis, independent predictors of HTLV-II infection included injection drug use (OR = 5.2; p < .001), black race (OR = 3.6; p < 0.001), age >35 years (OR = 3.3; p < .001) and a history of sex with a male injecting drug user (OR = 1.9; p < .001). Among women infected with HIV, the seroprevalence of HTLV-II was 11% compared with 6% for women at risk for HIV but not infected (p < .001). However, HIV was not an independent predictor of HTLV-II infection in multivariate analysis. CONCLUSIONS: This cross-sectional analysis confirms that HTLV-II is found commonly in HIV-infected women and uninfected women at risk for HIV in major urban areas throughout the United States and that HTLV-II is far more common than HTLV-I in these populations. Although injecting drug use is most strongly associated with HTLV-II infection, sexual transmission likely contributes to the high HTLV-II seroprevalence in this cohort.

Blotting, Western↗
PubMed1998

The involvement of poly(ADP-ribose) polymerase in the oxidative stress responses in plants.

In plants many biotic and abiotic stresses can cause secondary oxidative stress. Earlier work showed that, depending on the severity of the oxidative stress, plants can activate either cell protective genes or programmed cell death (PCD). Poly(ADP-ribose) polymerase (PARP) has been implicated as one of the enzymes in the apoptotic pathways induced by DNA damaging agents or oxidative stress. We show that in cultured soybean cells, PARP is involved in responses to mild and severe oxidative stresses, by mediating DNA repair and PCD processes, respectively. Addition of PARP inhibitors reduced the degree of cell death triggered by H2O2. Two windows of NAD consumption after H2O2 treatment were detected. Experiments with transient overexpression of Arabidopsis PARP cDNA promoted DNA repair and inhibited cell death caused by mild oxidative stress. However, following severe stress PARP overexpression increased cell death. Expression of antisense PARP produced the opposite effects: an increase in DNA nicks and inhibition of cell death at high, but not mild doses of H2O2.

Apoptosis↗
PubMed1998

Regulation of armadillo by a Drosophila APC inhibits neuronal apoptosis during retinal development.

We find that inactivation of a Drosophila homolog of the tumor suppressor APC (D-APC) causes retinal neuronal degeneration and pigment cell hypertrophy, a phenotype remarkably similar to that found in humans with germline APC mutations. Retinal degeneration in the D-APC mutant results from apoptotic cell death, which accompanies a defect in neuronal differentiation. Reduction in the Drosophila beta-catenin, Armadillo (Arm), rescues the differentiation defect and prevents apoptosis in the D-APC mutant, while Arm overexpression mimics D-APC inactivation. A mutation in dTCF, the DNA-binding protein required in Arm-mediated signal transduction, can eliminate the cell death without rescuing the differentiation defect in D-APC mutants. Uncoupling of these two Arm-induced processes suggests a novel role for the Arm/dTCF complex in the activation of apoptosis.

Adenomatous Polyposis Coli Protein↗
PubMed1998

The role of MAP4 expression in the sensitivity to paclitaxel and resistance to vinca alkaloids in p53 mutant cells.

Mutations in p53 change the sensitivity to cancer chemotherapeutic drugs. Whereas many drugs, including the vinca alkaloids, often become less effective when p53 is transcriptionally inactivated, several, most notably paclitaxel, may become more effective. In studying the underlying mechanism(s), we found that increased MAP4 expression, which occurs with transcriptionally silent p53, is associated with increased sensitivity to paclitaxel and decreased sensitivity to vinca alkaloids. Using murine fibroblasts transfected with MAP4, we directly demonstrated that the changes in drug sensitivity were associated with parallel alterations in drug-induced apoptosis and cell-cycle arrest. Immunofluorescent staining of the microtubule network revealed that cells with increased MAP4 expression displayed an increase in polymerized microtubules and an increased binding of fluorsceinated paclitaxel. Since MAP4 stabilizes polymerized microtubules, overexpression of this gene provides a plausible mechanism to explain the altered sensitivity to microtubule-active drugs in the presence of mutant p53.

3T3 Cells↗
PubMed1998

Activated protein C resistance in pediatric inflammatory bowel disease.

BACKGROUND: There is evidence for a hypercoagulable state in inflammatory bowel disease (IBD), and small vessel thrombosis has been identified in the bowel of patients with Crohn's disease, suggesting thrombosis as a possible etiologic factor. Activated protein C (APC) resistance is the most common inherited disorder leading to thrombosis and accounts for 30% to 40% of episodes of idiopathic venous thrombosis. METHODS: The prevalence of APC resistance was studied in 23 patients with IBD (17 with Crohn's disease, 6 with ulcerative colitis) and in 11 control subjects with recurrent abdominal pain or celiac disease, using an APC resistance screening method. RESULTS: One patient with Crohn's disease had a positive screen result, two patients (one with Crohn's, one with ulcerative colitis) had borderline results, and results in all of the control subjects were normal. One patient with Crohn's disease had a history of a thromboembolic event but had a normal screen result. CONCLUSIONS: Activated protein C resistance does not seem to play a major role in the etiology of the hypercoagulable state in inflammatory bowel disease.

Adolescent↗
PubMed1998

QT interval in children and infants receiving cisapride.

OBJECTIVES: Life-threatening arrhythmias and prolonged QT interval have been reported in adults and children using cisapride, a medication structurally similar to procainamide. Premature infants have reduced activity of cytochrome p-450, the system responsible for metabolism of cisapride, which could lead to QT prolongation. Therefore, we prospectively studied premature infants and children receiving cisapride to analyze the effect of prolonged cisapride therapy on QT interval. DESIGN: Premature infants in a neonatal intensive care unit and children seen at a pediatric gastroenterology clinic in a tertiary care hospital had electrocardiography-analyzed and -corrected QT interval measured before cisapride (0.8/mg/kg per day) therapy, and again after 1 month of therapy. If baseline electrocardiography was not performed initially, it was obtained after cessation of therapy. RESULTS: A total of 30 children participated in the study. Mean corrected QT interval was similar at baseline and at 1 month after therapy. Significant QT prolongation was not found, and no adverse effects were recorded. CONCLUSIONS: Corrected QT interval during prolonged cisapride therapy at 0.8 mg/kg per day appears to be similar for premature infants and children. An inherent trend toward QT prolongation was not detected in either group. In the absence of other risk factors that alter cisapride metabolism or predispose to arrhythmia, cisapride may be safe for use in premature infants as well as in children. Additional studies are needed to confirm these data.

Arrhythmias, Cardiac↗
PubMed1998

Utility of EMLA in the relief of pain associated with electroneurography.

Electroneurography (ENoG) is an electrodiagnostic procedure used to evaluate facial nerve deficit. A problem with application, however, is pain. Several studies have demonstrated that topical application of the eutectic mixture of lidocaine and prilocaine has an anesthetic effect on superficial and deep tissues. The present study was intended to determine if successful anesthesia of the trigeminal nerve could be achieved without altering the impulse transmission on the facial nerve. ENoG responses were measured at stimulation levels of 8, 16, 24, and 30 to 40 ma before and after Eutectic Mixture of Local Anesthetic (EMLA) application. A significant reduction in pain sensation was observed at stimulation levels of 8 and 16 ma while the amplitude of the response was not significantly changed. At the higher stimulation levels, namely, 24 and 30 to 40 ma, no significant reduction in pain or amplitude was observed. We concluded that, at moderate stimulation levels (> or =16 ma), EMLA reduces the pain associated with ENoG testing without affecting the amplitude of the muscular response.

Administration, Topical↗
PubMed1998

Identification of elf1, a beta-spectrin, in early mouse liver development.

Beta-spectrins play essential roles in cell-cell interactions and in the maintenance of cell polarity. Our aim was to identify beta-spectrin genes important for the establishment of hepatocyte polarity and differentiation. Using subtractive screening of cDNA libraries from early embryonic mouse livers (post-coital days 10, 11, and 12), we have isolated elf1 (embryonic liver fodrin 1), a differentially expressed beta-spectrin or fodrin (betaSpIIsigmaI). Elf1 encodes a 220-amino acid protein with an NH2 terminal actin-binding domain. In situ hybridization studies demonstrate elf1 expression initially in day 10 embryonic heart tissue, then in day 11-11.5 hepatic tissue. These studies suggest that elf1 may play a role in the emergence of hepatocyte polarity during liver development.

Amino Acid Sequence↗
PubMed1998

Open-label phase I study of combination therapy with zidovudine and interferon-beta in patients with AIDS-related Kaposi's sarcoma: AIDS Clinical Trials Group Protocol 057.

The aim of this study was to identify a safe and tolerable dose of recombinant interferon-beta (IFN-beta) used in conjunction with a fixed dose of zidovudine in patients with early-stage, good-prognosis AIDS-related Kaposi's sarcoma. We conducted a phase I, dose-escalation controlled trial of 22.5, 45 of 90 million units of IFN-beta given by daily subcutaneous injection with 500 mg per day of oral zidovudine. At the time of this study, this was standard of care for HIV infection. Patients were sequentially enrolled at three medical centers. Tumor response, drug tolerance, antiviral studies and CD4 changes were assessed. Four patients were enrolled at each dose level, and escalation proceeded when at least four patients had tolerated two weeks of therapy without dose-limiting toxicity. ACTG Kaposi's sarcoma tumor response criteria were used to assess response. Fifteen patients were enrolled. The combination of IFN-beta and zidovudine was well tolerated, and the dose-limiting toxicities were local skin necrosis and systemic symptoms. Despite generally good prognostic characteristics, only two patients achieved a clinical complete response and three addition patients had stable disease for a prolonged period of time (range 24-44 weeks). There was no correlation between baseline CD4 cell counts and tumor response, nor between the antiviral effect of IFN-beta as measured by decreases in immune-complex dissociated p24 antigen and tumor response. Higher doses of IFN-beta did not result in more tumor responses or in greater antiviral activity. The maximum tolerated dose of IFN-beta in combination with 500 mg per day of zidovudine was 45 million units by subcutaneous injection per day. IFN-beta is well tolerated in patients with AIDS-related Kaposi's sarcoma when used in conjunction with zidovudine. However, the antitumor response rate in good-prognosis patients is low. Further studies of this agent should be in the context of four-drug antiretroviral regimens where viral suppression is greatest and any antitumor activity of IFN-beta may be observed.

Anti-HIV Agents↗
PubMed1998

Type 2 diabetes in people of color.

Type 2 diabetes is a major public health concern for people of color throughout the United States. The prevalence of type 2 diabetes among African-Americans, Hispanics and American Indian/Alaskan Natives is from two to six times greater than that of the US non-Hispanic white population. Rates of end-stage renal disease, amputations, and diabetic retinopathy are also significantly higher. The medical risk factors of familial history, insulin resistance, obesity, history of gestational diabetes, impaired glucose tolerance, and physical inactivity are the same for all populations. The disproportionate impact of diabetes in people of color may be because of an interaction of genetic risk factors and environmental factors. Recognizing the impact of culture in disease management and self-care practices can improve diabetes care.

Black or African American↗
PubMed1997

The complete genome sequence of the gram-positive bacterium Bacillus subtilis.

Bacillus subtilis is the best-characterized member of the Gram-positive bacteria. Its genome of 4,214,810 base pairs comprises 4,100 protein-coding genes. Of these protein-coding genes, 53% are represented once, while a quarter of the genome corresponds to several gene families that have been greatly expanded by gene duplication, the largest family containing 77 putative ATP-binding transport proteins. In addition, a large proportion of the genetic capacity is devoted to the utilization of a variety of carbon sources, including many plant-derived molecules. The identification of five signal peptidase genes, as well as several genes for components of the secretion apparatus, is important given the capacity of Bacillus strains to secrete large amounts of industrially important enzymes. Many of the genes are involved in the synthesis of secondary metabolites, including antibiotics, that are more typically associated with Streptomyces species. The genome contains at least ten prophages or remnants of prophages, indicating that bacteriophage infection has played an important evolutionary role in horizontal gene transfer, in particular in the propagation of bacterial pathogenesis.

Bacillus subtilis↗
PubMed1997

The genetics and molecular structure of the Drosophila pair-rule gene odd Oz (odz).

Null alleles of the odz pair-rule gene have been generated as small Deficiency chromosome mutations. The true null phenotype of odz in segmentation is now seen to be very similar to that originally characterized, with each odd segment removed. No other previously isolated mutations in the genomic region proved allelic to odz. The generated Deficiencies covering the odz locus and immediately surrounding regions do not cover any other gene tested from that region. The entire odz gene has been cloned and mapped, and represents more than 120 kb of genomic DNA. The gene has been sequenced, except for two very large introns. Analysis of the upstream control region of the gene indicates the presence of a large number of putative binding sites for transcription factors that direct relevant developmentally regulated gene transcription.

Amino Acid Sequence↗
PubMed1997

[Esophageal carcinoma presenting as fever of unknown origin].

Fever of unknown origin presents both a clinical and diagnostic challenge and is usually caused by inflammatory and neoplastic diseases. We present a unique case of a previously healthy 77-year-old woman whose sole complaint was fever. Complete hospital investigation failed to reveal the underlying process. 4 months after the onset of fever, dysphagia appeared and she was then diagnosed as suffering from squamous cell carcinoma of the esophagus. The question of early barium swallow X-ray in such cases is raised.

Aged↗
PubMed1997

Covalent attachment of DNA oligonucleotides to glass.

A method for synthesizing DNA directly on glass is presented. The process is based on pretreatment of glass with boiling hydrochloric acid, thus exposing the hydroxyl groups of the glass. Phosphite-triester chemistry was used to directly attach the first nucleotide to a glass plate via a covalent bond between the hydroxyl group of the glass and the phosphate group of the protected deoxyribonucleotide. Standard molecular biology procedures, such as ligation and restriction digest, were efficiently performed on the glass synthesized oligonucleotide, with the added benefit of extreme ease of handling.

Biotechnology↗