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A Levine

Publications and source records attributed to A Levine.

At least 19 recordsLinked to original sources
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↗
PubMed1992

Epstein-Barr virus genotypes in AIDS-associated lymphomas are similar to those in endemic Burkitt's lymphomas.

PCR was used to screen EBV-positive lymphomas from endemic and sporadic Burkitt's lymphoma patients, including EBV-positive lymphomas derived from patients with HIV infection. Only 10% of sporadic lymphomas from either North America (1/15) or South America (2/14) were associated with the type 2 EBV strain, whereas 50% (8/16) of lymphomas from equatorial Africa and 46% (10/22) of HIV-associated lymphomas were positive for the type 2 strain. These data, in conjunction with previous reports, suggest that the proportions of strain types in Burkitt's lymphoma reflect the proportions of strain types in peripheral lymphocytes, and not simply the prevailing regional strain. The increased association of the type 2 strain in lymphocytes and lymphomas from HIV-infected individuals and from Africa may be a result of intermittent (malaria) or continuous (HIU) compromise of immune function in these populations.

Africa↗
PubMed1992

Cancer in AIDS.

Explore the source record for details and available documents.

AIDS-Related Opportunistic Infections↗
PubMed1992

Osteoblastoma of the spine.

Osteoid osteomas and osteoblastomas have similar histologic characteristics, although their clinical course in the spine may be significantly different. At the authors' institution, spinal osteoblastomas constituted 46% (30/65) of all osteoblastomas treated. Sixteen of the lesions occurred in the lumbar spine (53%), eight in the thoracic spine, and six in the cervical spine. In all regions of the spine, the posterior elements and pedicles were more frequently involved than the vertebral body. Twenty patients had pain or other symptoms for more than 12 months before diagnosis. Six of eight patients had thoracic lesions that demonstrated neurologic involvement. Twelve patients presented with painful scoliosis. Fourteen patients had lesions with well-circumscribed margins confined within the vertebral structure (Enneking Stage 2), and 16 had ill-defined margins with soft-tissue extension (Enneking Stage 3). Well-defined lesions were treated with curettage, with excellent results in 12 of 14 patients. The more extensive lesions were treated by intralesional excision (15/16) and adjuvant radiation therapy (9/16).

Adolescent↗
PubMed1991

Inhibition of promoter activity by methylation: possible involvement of protein mediators.

To study the relationship between DNA methylation and promoter activity we have methylated in vitro the promoters of the mouse metallothionein I gene and the herpes simplex virus thymidine kinase gene. We have transiently transfected these promoters fused to the human growth hormone in their methylated or unmethylated state into mouse L or F9 cells. Promoters methylated by methylase (M.) Hpa II and M.Hha I caused inhibition of reporter gene expression in L cells but not in F9 cells, while methylation of all CpGs by M.Sss I caused inhibition in both cell lines. Repression of promoter activity by M.Hpa II and M.Hha I methylation, but not by M.Sss I methylation, could be alleviated by cotransfection with an excess of untranscribable DNA methylated with M.Sss I. The methylated sites in nuclei isolated from the transfected L cells, but not F9 cells, were found to be protected from Msp I digestion. Taken together these results suggest that a factor present in L cells and missing in F9 cells mediates the methylation-directed inhibition of promoter activity. The ability of methylated DNA to overcome the inhibition seems to reflect competition for the mediator factor. Interestingly, treatment with Zn2+ ions brought about activation of the methylated promoter of the metallothionein gene. Similarly, butyrate could override the repression of the thymidine kinase methylated promoter. These activations were not accompanied by demethylation of the promoter or displacement of the mediator factor.

Animals↗
PubMed1991

The stringent response blocks DNA replication outside the ori region in Bacillus subtilis and at the origin in Escherichia coli.

When the Bacillus subtilis dnaB37 mutant, defective in initiation, is returned to permissive temperature after growth at 45 degrees C, DNA replication is synchronized. Under these conditions, we have shown previously that DNA replication is inhibited when the Stringent Response is induced by the amino acid analogue, arginine hydroxamate. We have now shown, using DNA-DNA hybridization analysis, that substantial replication of the oriC region nevertheless occurs during the Stringent Response, and that replication inhibition is therefore implemented downstream from the origin. On the left arm, replication continues for at least 190 x 10(3) base-pairs to the gnt gene and for a similar distance on the right arm to the gerD gene. When the Stringent Response is lifted, DNA replication resumed downstream from oriC on both arms, confirming that DNA replication is regulated at a post-initiation level during the Stringent Response in B. subtilis. Resumption of DNA synthesis following the lifting of the Stringent Response did not require protein or RNA synthesis or the initiation protein DnaB. We suggest, therefore, that a specific control region, involving Stringent Control sites, facilitate reversible inhibition of fork movement downstream from the origin via modifications of a replisome component during the Stringent Response. In contrast, in Escherichia coli, induction of the Stringent Response appears to block initiation of DNA replication at oriC itself. No DNA synthesis was detected in the oriC region and, upon lifting the Stringent Response, replication occurred from oriC. Post-initiation control in B. subtilis therefore results in duplication of many key genes involved in growth and sporulation. We discuss the possibility that such a control might be linked to differentiation in this organism.

Arginine↗
PubMed1991

Demethylation of CpG islands in embryonic cells.

DNA in differentiated somatic cells has a fixed pattern of methylation, which is faithfully copied after replication. By contrast, the methylation patterns of many tissue-specific and some housekeeping genes are altered during normal development. This modification of DNA methylation in the embryo has also been observed in transgenic mice and in transfection experiments. Here we report the fate in mice of an in vitro-methylated adenine phosphoribosyltransferase transgene. The entire 5' CpG island region became demethylated, whereas the 3' end of the gene remained modified and was even methylated de novo at additional sites. Transfection experiments in vitro show that the demethylation is rapid, is specific for embryonic cell-types and affects a variety of different CpG island sequences. This suggests that gene sequences can be recognized in the early embryo and imprinted with the correct methylation pattern through a combination of demethylation and de novo methylation.

Adenine Phosphoribosyltransferase↗
PubMed1991

Germinal center T cells are distinct helper-inducer T cells.

Germinal centers (GCs) contain a significant number of CD4+ T cells, but what role these T cells may play in the development of GC B cells has not been determined. To gain insight into their role, we studied the phenotype of GC T cells and the lymphokines secreted by GC T cells isolated from human tonsils obtained after tonsillectomies. In addition to confirming that a large fraction of GC T cells are Leu-7(CD57)+ and Leu-8-, we found that they have no binding sites for peanut agglutinin. Furthermore, we found that they are CD45RA- and CD45R0+, the phenotype of helper-inducer T cells. We also found that Leu-7(CD57)+ cells display CD69, a phenotypic marker of very early cell activation, but do not display three other markers of cell activation: CD25 [interleukin-2 (IL-2) receptor], CD71 (transferrin receptor), and DR. When isolated, Leu-7(CD57)+ cells were stimulated in vitro with a mitogen that can induce peripheral blood T cells with the helper-inducer phenotype to produce various cytokines, Leu-7(CD57)+ cells did not produce IL-2, interleukin-4 (IL-4), interferon-gamma (IFN-gamma) or tumor necrosis factor-alpha (TNF-alpha) in significant amounts. Taken together, GC T cells from a distinct subpopulation of T cells with helper-inducer phenotype by their histologic location, by their surface phenotype, and by their ability to produce lymphokines. This finding is consistent with the possibility that GC T cells have been selectively recruited to actively help B cells develop in GCs.

Antigens, CD↗
PubMed1990

Case report 618. Metastatic angioblastic meningioma.

A patient with a history of angioblastic meningioma 7 years previously developed lytic metastatic disease to the femur at two separate sites. The controversy in terminology of angioblastic meningioma and hemangiopericytoma and the similarity in radiological and pathological appearance of primary and metastatic hemangiopericytoma of bone illustrate the need for an accurate clinical history to arrive at a correct diagnosis.

Adult↗
PubMed1990

Case report 594: Osseous sarcoidosis (osteolytic) of lumbar spine and pelvis.

A case of destructive osseous sarcoidosis involving the lower lumbar spine, sacrum, and pelvis has been presented. The pattern of multiple small lytic lesions without sclerosis in this distribution has not been described previously. Identification of these lesions was only possible by computed tomography and differentiation from metastatic disease required open biopsy.

Adult↗
PubMed1990

Psychosocial status at initiation of cancer treatment and survival.

Ninety-two newly diagnosed patients with hematologic malignancies treated with chemotherapy, and 47 patients with rectal cancer treated with abdominal-perineal resection were prospectively studied to assess the relationship between mood and survival. Hematology patients were measured within one week of diagnosis and were remeasured at six months. Rectal cancer patients were measured within three months of surgery and remeasured six months later. Medical records were abstracted to obtain data on treatment given, disease characteristics and outcome of treatment. On univariate analyses using Cox regression, we examined the effect of depression, coping style and locus of control on survival. None of these variables were found to be significantly related to survival whether assessed at intake or six months later. Furthermore there were no statistically significant correlations between these factors and subsequent survival at two years or with long-term survival. Biological prognostic variables including extent of disease for rectal cancer patients and severity of specific type of hematologic cancer were significantly related to survival. Although psychosocial adjustment is important for the quality of life experienced by cancer patients it was not related to length of survival in this study. Further exploration of this issue should be conducted using patients with a single site and preferrably an early stage of disease.

Adaptation, Psychological↗
PubMed1990

Adenofibroma of the uterus: multiple recurrences following wide local excision.

The uterine adenofibroma is a form of mixed mesodermal tumor in which both epithelial and stromal components are benign. A case is presented in which a patient with this lesion was treated with excision of the tumor rather than hysterectomy. Two years later, she developed a recurrence of the lesion, which was again treated with wide local excision. A hysterectomy was done 9 months later, and a polypoid lesion was noted in the fundus of the uterus which on histologic examination was thought to be potentially either an adenofibroma precursor or a maturation of the previous cellular adenofibroma. Since uterine adenofibroma usually occurs in older patients, the standard treatment has been hysterectomy. Because of this patient's age, she was initially treated with a more conservative approach. However, despite the fact that the uterine adenofibroma is a benign lesion, it has an obvious potential to recur when treated conservatively.

Adenofibroma↗
PubMed1990

Treatment of advanced Kaposi's sarcoma using a combination of bleomycin and vincristine.

Eighteen patients with disseminated AIDS-related Kaposi's sarcoma (KS) and compromised bone marrow function were treated with a relatively non-myelosuppressive regimen of bleomycin and vincristine (BV). At study entry, the patients presented with the following median laboratory values: hemoglobin of 9.5 g/dl, granulocyte counts of 1,173/mm3, platelet counts of 218,000/mm3, and CD4 lymphocyte counts of 58/mm3. All patients had extensive Kaposi's sarcoma. Nine patients had visceral involvement: four with pulmonary involvement, two with gastrointestinal involvement, and three with both. Following a median number of seven cycles of biweekly chemotherapy, complete or partial tumor responses were achieved in 13 patients (72%). Two patients experienced bleomycin-induced skin toxicities, whereas 10 others (55%) experienced peripheral sensory neuropathy requiring vincristine dose reductions. Opportunistic infections had occurred in 11 patients prior to initiation of chemotherapy and in 16 after initiation of chemotherapy. Despite the frequent development of opportunistic infections, BV chemotherapy was relatively well tolerated and resulted in a high response rate in this patient population that presented with suboptimal marrow function and extremely low CD4 lymphocyte counts.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Fibronectin/laminin and their receptors in aberrant growth control in FR3T3 cells transformed by Ha-ras oncogene and epidermal growth factor gene.

FR3T3 cells transfected with either the Ha-ras oncogene or the epidermal-growth-factor (EGF) gene demonstrate the transformed phenotype as indicated by in vitro and in vivo criteria. We have examined non-transformed FR3T3 cells as well as Ha-ras-oncogene-transformed and EGF-gene-transformed cells for expression of cell surface fibronectin and cell surface laminin. Fibronectin was absent from the surface of the Ha-ras-oncogene-transformed cells but present on both the EGF-gene-transformed cells and the non-transformed FR3T3 cells. Laminin was present on the cell surface in all 3 lines. The lack of surface fibronectin on the Ha-ras-oncogene-transformed cells was associated with reduced fibronectin production as indicated by immunoblotting of whole cell extracts and by ELISA. Concomitantly, there was a significant reduction of fibronectin binding by the Ha-ras-oncogene-transformed cells was compared to their EGF-gene-transformed and non-transformed counterparts. The Ha-ras-oncogene-transformed cells demonstrated reduced cell-substrate adhesiveness relative to the other two cell lines, as indicated by rates of attachment and spreading on plastic culture dishes in the presence of bovine serum albumin. They also demonstrated reduced adhesiveness in response to fibronectin but not laminin. Taken together, our results suggest that aberrant expression of fibronectin/fibronectin receptors is associated with Ha-ras-oncogene-induced transformation. In contrast, transformation by the EGF gene does not appear to involve aberrant expression of fibronectin/fibronectin receptors.

Animals↗
PubMed1989

Overreplication of the origin region in the dnaB37 mutant of Bacillus subtilis: postinitiation control of chromosomal replication.

When the Bacillus subtilis dnaB37 mutant, defective in initiation, is returned to permissive temperature after accumulation of initiation proteins at 45 degrees C, we have shown, by extensive DNA.DNA hybridization analysis, that the origin region is replicated in excess (approximately 2-fold). However, this replication is limited to a region of about 120-175 kilobases on either side of the origin. This has been confirmed by autoradiographic analysis of the overreplicated region. During the second round of synchronized replication at 30 degrees C, replication in fact appears to resume from the stalled forks on either side of the origin. We propose that in B. subtilis, in addition to a first level of control at the origin, a second level of control exists downstream of the origin in order to limit overreplication of the chromosome. These two controls might normally be tightly coupled. We suggest that the second level of control is exerted through the reversible inhibition of replisome movement at specific regions on either side of the origin.

Bacillus subtilis↗