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Biomedical subjects

A Levine

Publications and source records attributed to A Levine.

At least 91 records · Page 5Linked to original sources
PubMed1994

Cytokine-induced immune deviation as a therapy for inflammatory autoimmune disease.

The properties and outcome of an immune response are best predicted by the lymphokine phenotype of the responding T cells. Cytokines produced by CD4+ T helper type 1 (Th1) T cells mediate delayed type hypersensitivity (DTH) and inflammatory responses, whereas cytokines produced by Th2 T cells mediate helper T cell functions for antibody production. To determine whether induction of Th2-like cells would modulate an inflammatory response, interleukin 4 (IL-4) was administered to animals with experimental allergic encephalomyelitis (EAE), a prototypic autoimmune disease produced by Th1-like T cells specific for myelin basic protein (MBP). IL-4 treatment resulted in amelioration of clinical disease, the induction of MBP-specific Th2 cells, diminished demyelination, and inhibition of the synthesis of inflammatory cytokines in the central nervous system (CNS). Modulation of an immune response from one dominated by excessive activity of Th1-like T cells to one dominated by the protective cytokines produced by Th2-like T cells may have applicability to the therapy of certain human autoimmune diseases.

Animals↗
PubMed1994

Odd Oz: a novel Drosophila pair rule gene.

We have identified a novel pair rule gene in Drosophila, odd Oz (odz). Every odd-numbered body segment is deleted in odz mutant embryos. The odz gene product is strongly expressed in the embryonic central nervous system and heart, and both of these tissues are malformed in mutant embryos. Odz represents the only known pair rule gene that does not encode a transcription factor. Instead, it encodes a protein with EGF-like repeats homologous to those of the extracellular matrix protein tenascin. The protein is also a putative transmembrane tyrosine kinase substrate. On the basis of its structure, odz must act in a cellularized embryo. This is consistent with odz expression, whose temporal appearance is indicative of a very late-acting pair rule gene.

Amino Acid Sequence↗
PubMed1994

Overview of the space environmental effects observed on the retrieved Long Duration Exposure Facility (LDEF).

The Long Duration Exposure Facility (LDEF), which encompassed 57 experiments with more than 10,000 test specimens, spent 69 months in low Earth orbit (LEO) before it was retrieved by the Space Shuttle in January 1990. Hundreds of LDEF investigators, after studying for over two years these retrieved test specimens and the onboard recorded data and systems hardware, have generated a unique first-hand view of the long term synergistic effects that the LEO environment can have on spacecraft. These studies have also contributed significantly toward more accurate models of the LEO radiation, meteoroid, manmade debris and atomic oxygen environments. This paper provides an overview of some of the many LDEF observations and the implications these can have on future spacecraft such as Space Station Freedom.

Aluminum↗
PubMed1994

Urinary free cortisol values in children under stress.

Children with adrenocortical insufficiency are commonly instructed to increase their baseline glucocorticoid replacement doses by three to five times during periods of stress such as surgery or febrille illness. We conducted this to determine whether these recommendations reflect the actual change in urinary free cortisol (UFC) output during stress. The 24-hour UFC excretion was determined in 78 children who were admitted to a general pediatric department or intensive care unit with temperature > 38.7 degrees C, after major surgery, or during status epilepticus; we reevaluated 43 of the patients 2 weeks after recovery. In addition, the 24-hour UFC levels were determined in 127 healthy children aged 1.8 to 17 years. The UFC level positively correlated with age (r = 0.254; p < 0.001). The amount of UFC per gram of creatinine was inversely correlated with age (r = 0.255; p < 0.001). The amount of UFC per surface area was independent of age. The mean change in the level of UFC per square meter surface area was highest among children who had cardiothoracic surgery and those with multiple trauma. The increase in UFC level during bacterial infection was significantly greater than that during viral infection. The current recommendation to increase the dose to three to five times the baseline glucocorticoid dose during times of stress may underestimate the changes in UFC found in some patients with major surgery, trauma, or certain serious bacterial infections. Production rate studies are needed to prove this point.

Abdomen, Acute↗
PubMed1994

Primary versus secondary and central versus consequence-related control in HIV-positive men.

Two dimensions of perceived control (primary vs. secondary and central vs. consequence-related) were examined in a sample of 104 HIV-positive men. Two hypotheses regarding the use of primary control (acting to achieve specific outcomes) and secondary control (acceptance) were supported: The use of both primary and secondary control was associated with better adjustment. Secondary control served a protective role at lower levels of primary control, but was not associated with adjustment at higher levels of primary control. The 2 hypotheses regarding central control (over the infection) and consequence-related control (over consequences of the infection) were also supported. Perceptions of consequence-related control were higher than perceptions of control over HIV and more strongly associated with low depression.

Adaptation, Psychological↗
PubMed1993

Histone H1-mediated inhibition of transcription initiation of methylated templates in vitro.

The detailed mechanism underlying the inhibition of transcription by DNA methylation is still obscure. Chromatin structure has frequently been proposed as a role player in this mechanism. Histone H1 is a known key element in the formation and stabilization of chromatin fibers. We describe here experiments designed to examine the effect of DNA methylation on the binding of histone H1 to DNA and the consequent inhibitory effect of the bound histone H1 on in vitro transcription. The results of these experiments showed a clear preferential binding of histone H1 to methylated DNA as compared with unmethylated DNA. The in vitro transcription assay indicated that transcription of methylated templates was inhibited at a lower histone H1/DNA ratio than of unmethylated templates, and that the extent of inhibition depends on the density of methyl groups in the promoter region. This inhibition of in vitro transcription was alleviated efficiently by methylated competitor DNA, whereas, under similar conditions, almost no effect was observed with unmethylated competitor. Experiments designed to pinpoint the stage in the transcription process that was suppressed by the preferred binding of histone H1 to methylated template revealed that inhibition occurred at the initiation and not at the elongation level.

Binding Sites↗
PubMed1993

Identification of T- and B-cell epitopes associated with a restricted component of the Epstein-Barr virus-induced early antigen complex.

Experiments were designed in an attempt to identify T- and B-cell epitopes expressed on the 17-kDa early-antigen-restricted (EA-R) polypeptide of the EBV-induced early antigen complex. Using Berzofsky's algorithm, 3 hypothetical T-cell epitopes on p17 were synthesized and employed in EBV-specific lymphoproliferative assays. Lymphocytes from all EBV-infected donors responded against one of these epitopes (p17.1) irrespective of their serological status relative to antibodies to EA-R. Both CD4+ and CD8+ T-cell subpopulations from seropositive donors proliferated in the presence of p17.1 in short-term cultures. These experiments therefore identified one T-cell epitope on the 17-kDa polypeptide. In contrast, sera from anti-Ea antibody-positive individuals reacted with all 3 synthetic peptides to varying degrees, with p17.1 being the most frequently reactive epitope. When the sera were grouped according to diagnosis, it was noted that 82% of the sera from patients with aggressive lymphomas, whether Africans with Burkitt's lymphoma or North Americans with intermediate-grade large-cell or high-grade B-cell lymphoma, contained antibody reactive with p17.1, while 64% were reactive with p17.2 and 29% with p17.3. In contrast, high anti-EA antibody-positive sera from nasopharyngeal carcinoma patients were relatively less reactive with these synthetic peptides (23% positive with p17.1; 19% with p17.2; and 13% with p17.3). These results therefore identified 3 B-cell EA-R epitopes which might be potentially useful for clinical or epidemiological studies of EBV-associated lymphoproliferative diseases.

Amino Acid Sequence↗
PubMed1993

Primary renal carcinoid tumor.

We report a case of primary renal carcinoid tumor. Only 13 prior cases are documented in the literature. The tumor fulfilled both histologic and immunochemical criteria for carcinoid. In addition, we employed new diagnostic modalities (i.e., magnetic resonance imaging and chromogranin-A levels) not used in prior published reports. A review of the literature is presented.

Adult↗
PubMed1993

Frequency of adult T-cell leukaemia/lymphoma and HTLV-I in Ibadan, Nigeria.

Sera from a small sample of adult blood donors, healthy school children and patients with lymphoma, leukaemia, non-haematologic cancer, congenital and inflammatory disorders from Ibadan, Nigeria were screened for HTLV-I antibody by an enzyme-linked immunoabsorbent assay and confirmed by investigational Western blot. Seventy-nine of 236 positively screened samples could not be tested for confirmation. Seropositive reactivity was observed in nine of 123 blood donors, and 3 of 46 healthy school children but banding patterns on Western blot were often sparse. Among non-Burkitt's non Hodgkin's lymphoma patients six of 30 were HTLV-I positive including four of four with clinical features of adult T-cell leukaemia (ATL). Other clinical conditions had a frequency of positivity indistinguishable from healthy donors. Western blot patterns ranged from strong with multiple bands, which were uncommon, to those with only p24 and p21 envelope positive which were frequent. Given the relative paucity of clinical ATL and the unusual Western blot patterns the true rate of HTLV-I infection may be lower than estimated. It is possible that a cross-reactive HTLV-I-like virus accounts for this pattern.

Adolescent↗
PubMed1993

Phase I trial of m-BACOD and granulocyte macrophage colony stimulating factor in HIV-associated non-Hodgkin's lymphoma.

The use of full-dose intensive regimens of chemotherapy in patients with HIV-associated lymphoma has often resulted in severe toxicity, treatment delay, and reduced subsequent dosing. We conducted a Phase I trial to evaluate the toxicity of the combination of m-BACOD (methotrexate, Bleomycin, doxorubicin, cyclophosphamide, vincristine, dexamethasone) with granulocyte-macrophage colony stimulating factor (GMCSF) in these patients. A total of 17 patients were entered and treated at three dose levels of m-BACOD in combination with a fixed dose of GMCSF. Eight patients received standard dose m-BACOD plus GMCSF without experiencing dose-limiting hematologic toxicity, although significant nonhematologic toxicity was seen. We conclude that it is feasible to treat patients with HIV-associated lymphoma using standard dose m-BACOD plus GMCSF, but further study is needed to determine whether full-dose regimens improve survival when compared with reduced dose regimens in these individuals.

AIDS-Related Opportunistic Infections↗
PubMed1993

Effects of etching time on enamel bond strengths.

This study evaluated the effects of etching time on bond strengths of composite to enamel. Proximal surfaces of extracted molars were etched with either a conventional etchant (35% phosphoric acid) or one of two dentin/enamel conditioners, 10% maleic acid (Scotchbond Multi-Purpose Etchant), or a solution of oxalic acid, aluminum nitrate, and glycine (Gluma 1 & 2 Conditioner). Each agent was applied for 15, 30, or 60 seconds. Specimens etched with 35% phosphoric acid had the highest mean bond strengths at each etching time. At the manufacturer's recommended application times, the other two agents gave significantly lower shear bond strengths than phosphoric acid.

Acid Etching, Dental↗
PubMed1992

Methylation in the preinitiation domain suppresses gene transcription by an indirect mechanism.

Although the first observations of the inhibitory effect of methylation on gene activity were made almost a decade ago, the mechanism by which methyl groups affect transcription is still obscure. Here we use engineered promoters methylated in vitro in transient transfections to study the mechanism by which methylation mediates promoter repression. The results clearly show that the location of the methyl groups within the promoter region determines the extent of promoter repression. The most effective suppression was observed when methylation was in the preinitiation domain. The results also support a previous suggestion that a mediator protein is involved in the mechanism of promoter inhibition. The suppressor effect of methylation at sequences flanking the TATA box can be partially overcome in the presence of the simian virus 40 enhancer. In addition, results obtained by transient thymidine labeling of Ltk- cells that were transfected with a methylated thymidine kinase gene from herpes simplex virus, at the level of approximately one template per cell, further support the conclusion that methylation affects primarily transcription preinitiation.

Animals↗
PubMed1992

An incest survivors' therapy group.

A weekly therapy group for women who have been incest victims and are residents of Odyssey House, a therapeutic community for drug abusers, is described. Women participating in the group have a significantly greater retention and graduation rate than other women in the program. The group reduces isolation; helps in dealing with denial; clarifies relations with children, other family members, and significant others; and facilitates dealing with incest-related guilt and shame. The impressive therapeutic progress of the incest survivors, which is attributable to the group, suggests the possible utility of such a group for other therapeutic communities and treatment programs.

Adolescent↗
PubMed1992

Adriamycin, bleomycin and vincristine chemotherapy with recombinant granulocyte-macrophage colony-stimulating factor in the treatment of AIDS-related Kaposi's sarcoma.

OBJECTIVE: To determine the maximum tolerated dose of granulocyte-macrophage colony-stimulating factor (GM-CSF) that would reduce the severity and duration of neutropenia from combination cytotoxic chemotherapy in the treatment of AIDS-related Kaposi's sarcoma (KS). DESIGN: Phase I, dose escalation. SETTING: Outpatient clinic of a university hospital. PATIENTS: HIV-seropositive patients with advanced KS. INTERVENTIONS: Combination chemotherapy consisting of adriamycin, bleomycin, and vincristine (ABV), with escalating doses of recombinant human GM-CSF (rhGM-CSF). Patients were treated for a median of six cycles (range, between two and seven cycles) of biweekly chemotherapy with GM-CSF administered in divided daily subcutaneous doses on days 2-12. Serum cytokine levels of interleukin (IL)-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha were measured before, during, and after therapy to correlate with response to therapy. RESULTS: A GM-CSF dose of 250 micrograms/m2 was well tolerated, whereas the next dose escalation, of 500 micrograms/m2, was associated with dose-limiting toxicities, including grade 3 fever, fatigue, and diarrhea. GM-CSF produced predictable cyclic increases in granulocytes, allowing for delivery of full-dose chemotherapy on schedule. All patients were HIV-p24-antigen-negative at study entry; no activation of p24 antigenemia was observed after repeat testing. Consistent changes in cytokine levels were not observed. Responses included one complete and three partial responses, and two patients with stable disease parameters. CONCLUSIONS: We conclude that GM-CSF can be administered safely to patients with AIDS-related KS receiving myelosuppressive chemotherapy, resulting in granulocytic response, without up-regulation of HIV p24 antigen levels in serum.

Acquired Immunodeficiency Syndrome↗