Biomedical subjects

D A Wolf

Publications and source records attributed to D A Wolf.

At least 37 records · Page 2Linked to original sources

PubMed1997

The division of family labor: care for elderly parents.

We consider the division of caregiving efforts among the children of older, functionally limited parents. Our model of parental care assumes that care decisions are made in the context of an extended family, with each child taking into account not only the parent's needs and the child's own circumstances, but also the characteristics and actual care behavior of siblings. We propose a simultaneous-Tobit statistical framework that embodies these assumptions. The model is estimated using data from the 1993 Asset and Health Dynamics Among the Oldest Old (AHEAD) study. The findings indicate that a child's hours of parent care are reduced, but on much less than a one-for-one basis, as the parent-care hours of siblings increase. We also find that a child's supply of parent-care hours is reduced by having sisters, holding constant the care efforts of siblings.

Aged↗

PubMed1997

Selection of children to provide care: the effect of earlier parental transfers.

We use the first wave of data from the Asset and Health Dynamics Among the Oldest Old (AHEAD) study to examine the effects of past parent-to-child financial transfers on selection of a child to provide assistance with basic personal care for unmarried parents. We estimate a fixed-effects conditional logit model and find a positive and significant association between past financial transfers and a child's current helping behavior. The coefficient of past financial transfers is in the direction hypothesized, and its magnitude is 80% as large as that of gender, a well-documented powerful predictor of parental caregiving. There appears to be substantial evidence that earlier parent-to-child financial gifts play a role in determining which child in the family will provide assistance.

Aged↗

PubMed1997

Intracranial chondromyxoid fibroma. Report of a case and review of the literature.

Chondromyxoid fibroma is an unusual benign tumor of cartilaginous derivation. We describe a rare example of chondromyxoid fibroma of the frontal-sphenoid junction with orbital infiltration in a 35-year-old Hispanic woman who presented with frontal headaches. Gross total excision was performed. The excised mass was composed of neoplastic cells with chondrocytic features within a myxoid matrix. Bony infiltration was present without infiltration of dura mater or brain tissue. The lack of mitotic activity, low cell density, lack of nuclear pleomorphism, and a fused lobular architectural pattern indicated that the lesion was a chondromyxoid fibroma. The lack of hyaline cartilage helped differentiate the lesion from enchondroma. Our case demonstrates the uncommon occurrence of intracranial chondromyxoid fibroma with orbital infiltration. When faced with an intracranial chondrocytic tumor, it is important to distinguish this neoplasm from enchondroma and chondrosarcoma.

Adult↗

PubMed1997

Mononuclear phagocyte hydrolytic enzyme activity associated with cerebral HIV-1 infection.

In patients with HIV encephalitis, activated macrophages and microglial cells in the brain are infected by the human immunodeficiency virus (HIV-1). Immune activation can release neurotoxic chemicals including cytokines, free radicals, autocoids, and hydrolytic enzymes. In this study, the presence of hydrolytic enzymes in acquired immune deficiency syndrome (AIDS)-related neurodegeneration was addressed. Activities of four lysosomal hydrolases were assayed in the frontal lobe of 69 males who died with AIDS and 31 age-matched control men. Activities of all four enzymes were increased significantly (1.6 to 3.6 times) in white matter of patients with AIDS. Less pronounced increases were present in cerebral cortex. Of 69 of the subjects with AIDS, 50 (72%), had at least one abnormally active enzyme. Patients with HIV encephalitis and other neuropathological changes were affected as were many subjects without any clear neuropathological anomaly. Lysosomal cathepsin D immunostaining revealed increased lysosomes within perivascular macrophages, multinucleated cells, activated microglial cells, and hypertrophic astrocytes. Increased enzyme activity was correlated significantly with assay results for HIV-1 DNA using the polymerase chain reaction. The release of acid hydrolases associated with cerebral HIV-1 infection could lead to unopposed hydrolysis of matrix and surface proteins. These post-translational disturbances could contribute to white matter and synaptic injury in AIDS.

Acetylgalactosamine↗

PubMed1997

Proteolysis in the myelopathy of acquired immunodeficiency syndrome: preferential loss of the C-8 component of myelin basic protein.

Many patients with AIDS have a myelopathy characterized by vacuolization of spinal cord white matter. The biochemical and molecular changes underlying this myelin disturbance have not yet been characterized. Myelin basic protein (MBP) is potentially important because it is a key structural protein of myelin with roles in compaction and stabilization. In the present study, we describe the steady-state protein concentration of MBP in 46 patients with AIDS and 12 control subjects at autopsy. Patients with myelopathy exhibited no change in the abundance of the predominant 18.5- and 17.2-kd isoforms, but a 14-kd MBP-immunoreactive degradation fragment was increased significantly. MBP degradation correlated significantly with the severity of histopathologic changes, including neutral lipid deposition, the density of vacuolated fibers, and the number of ferritin-stained activated microglia. Alkaline gel electrophoresis of isolated MBP showed preferential loss of the least cationic isomer (C-8). The concentration of MBP RNA in slot blots was normal in cords exhibiting myelopathy, and the ratio of mRNA corresponding to the 18.5- and 17.2-kd MBP isoforms, measured using reverse transcriptase-PCR, was not altered. This study suggests that mononuclear phagocyte-mediated degradation of MBP may play a role in AIDS myelopathy, and the preferential loss of the C-8 component of MBP may have mechanistic implications.

Acquired Immunodeficiency Syndrome↗

PubMed1996

Disruption of re-replication control by overexpression of human ORC1 in fission yeast.

Initiation of DNA replication in Saccharomyces cerevisiae requires the binding of the origin recognition complex (ORC) to autonomously replicating sequences. HsORC1, a recently identified human protein related to yeast Orc1p and Cdc6p/Cdc18p, may be a component of the replication initiation complex in human cells. We have independently isolated the gene for HsORC1 and begun to address its function in eukaryotic DNA replication and its relationship to Cdc18p. Although HsORC1 failed to rescue the temperature-sensitive S. pombe cdc18-K46 strain, overexpression in a wild-type strain led to continuous DNA synthesis in the absence of mitosis. Deletion mutagenesis identified a short N-terminal region of HsORC1 that contains potential phosphorylation sites for cyclin-dependent kinase (CDK) as being sufficient to induce re-replication. In addition, we found that HsORC1 is an efficient substrate for CDKs in vitro. We propose that perturbation of the re-replication control by overexpression of HsORC1 is due to a titration of components involved in inactivating Cdc18p upon initiation of replication.

Cell Compartmentation↗

PubMed1996

Expression of a highly conserved oncofetal gene, TA1/E16, in human colon carcinoma and other primary cancers: homology to Schistosoma mansoni amino acid permease and Caenorhabditis elegans gene products.

The peptides encoded by the rat liver oncofetal cDNA TA1 and the human lymphocyte activation gene E16 display a high degree of homology with coding regions recently identified in Schistosoma mansoni and Caenorhabditis elegans. Previous studies showed that up-regulation of TA1/ E16 expression was associated with rat hepatocarcinogenesis and human tumor cell lines; therefore, we analyzed several primary human tumors including a panel of 20 colon carcinomas to evaluate the relationship of TA1/E16 RNA and protein expression to neoplasia. A 4.0-kb transcript was detected in all but one colorectal carcinoma but not in normal colon or specimens of inflammatory bowel disease. Steady-state TA1/E16 mRNA levels varied considerably between carcinomas and did not correlate simply with mitotic index, modified Dukes' stage, or tumor size. TA1/E16 message also was detected in adenocarcinomas from breast, endometrium, salivary gland, and esophagus. Western blot analysis using antibodies against TA1/E16-deduced peptides identified major reactive bands of approximately 35 and 19 kDa in neoplasms but not in normal tissue. Immunoperoxidase staining localized the protein primarily to the supranuclear region of colon carcinoma cells, whereas normal epithelial cells were negative. Heterogeneous staining was found in villous adenomas with focal intramucosal adenocarcinoma but was negative in tubular adenomas, suggesting that expression of TA1/E16 may correlate with neoplastic progression in the colon. Up-regulation of this gene in various human cancers suggests a common role in the carcinogenic process and possible application as a tumor marker.

Adult↗

PubMed1996

Incarceration and the acquired immunodeficiency syndrome: autopsy results in Texas prison inmates.

The Texas Department of Criminal Justice (TDCJ) houses many subjects with acquired immunodeficiency syndrome (AIDS) who receive medical care in a comprehensive AIDS treatment center. In this case-control autopsy survey, we compared pathological outcomes of TDCJ inmates treated at the center (n = 155) with nonincarcerated patients who died during the same period (n = 155). Using multiple regression analysis and a proportional hazards model, survival time in the prisoners was equivalent to that in the controls. With few exceptions, the prevalences of opportunistic viral, fungal, protozoal, and bacterial infections contributing to mortality were equivalent between groups. Mycobacterium tuberculosis was isolated more frequently in the inmates, and M avium intracellulare was isolated less frequently (P < .0001). The inmates had a higher prevalence of bacterial infection of the central nervous system (CNS) (9.1% v 1.4%; P < .006); half of all CNS bacterial infections were caused by M tuberculosis. Inmates had significantly lower prevalences of vacuolar myelopathy (P < .006) and severe wasting disease (P < .0009). We conclude that survival of prison inmates with AIDS treated in a comprehensive AIDS treatment center was equivalent to that of nonincarcerated subjects with AIDS. Prevalences of certain complications of AIDS differed in the inmates, showing that the prison environment influenced some of the underlying causes of AIDS morbidity and mortality.

AIDS-Related Opportunistic Infections↗

PubMed1995

Ultraviolet B irradiation-induced G2 cell cycle arrest in human keratinocytes by inhibitory phosphorylation of the cdc2 cell cycle kinase.

In response to genotoxic stress, cell cycle progression can be arrested at certain checkpoints which serve to maintain genomic integrity. We have investigated the mechanism of ultraviolet B (UVB) irradiation-induced cell cycle arrest in normal human keratinocytes and in the HaCaT keratinocyte cell line which carries mutant p53 tumour suppressor protein. While only normal keratinocytes showed a delay in G1 following sublethal UVB irradiation both cell types exhibited prolonged G2 arrest attributable to rapid inhibition of cyclin B-associated cdc2 kinase activity. This inhibition coincided with increased tyrosine phosphorylation of cdc2 and was reversed by the cdc25C phosphatase in vitro. The data indicate that UVB-induced G2 arrest in mammalian cells is mediated by inhibitory tyrosine phosphorylation of cdc2 and acts as a defense mechanism against DNA damage irrespective of the cells' p53 status.

CDC2 Protein Kinase↗

PubMed1995

Variable pause positions of RNA polymerase II lie proximal to the c-myc promoter irrespective of transcriptional activity.

Transcriptional activation of the c-myc proto-oncogene is mediated by the transition of promoter proximal, paused RNA polymerase II (pol II) into a processive transcription mode. Using a transcription assay which allows the high resolution mapping of transcriptional complexes in intact nuclei, we have characterized the promoter proximal pause positions of pol II. Pol II paused in a nucleosome-free region close to the transcription start site as well as further downstream, between positions +17 and +52. These pause positions were detected in both transcriptionally active and inactive c-myc genes. Pharmacological inhibition of the C-terminal phosphorylation of the large subunit of pol II did not affect the paused transcription complexes, but had an inhibitory effect on transcription of nucleosomal DNA downstream of position +150. The different properties of pol II proximal and distal to the promoter suggest a model in which c-myc transcription is regulated by the activation of promoter bound polymerases.

Base Sequence↗

PubMed1995

A complex between E2F and the pRb-related protein p130 is specifically targeted by the simian virus 40 large T antigen during cell transformation.

The p130 protein is a recently cloned member of the retinoblastoma protein family. We show here that transformation of NIH3T3-L1 fibroblasts (L1 cells) by the simian virus 40 large T antigen (LTAg) depends on the disruption of DNA binding complexes between transcription factor E2F and p130. LTAg binds to the pocket region of p130 in vivo and disrupts the E2F-p130 complexes. E2F-p130 complexes are present only in quiescent L1 cells and disappear at the G1/S phase boundary concomitantly to induction of DNA synthesis and expression of the E2F-regulated cdc2 gene. p130 is a substrate of cyclin-dependent kinase 2 (Cdk2) in vitro and associates with a Cdk in vivo which is activated upon serum stimulation in late G1. Overexpression of p130 inhibits cdc2 promoter activity and entry of quiescent L1 cells into S phase. The results demonstrate that p130 is negative regulator of cell cycle progression which is specifically targeted by LTAg during cell transformation.

3T3 Cells↗

PubMed1995

The pRb-related protein p130 is a possible effector of transforming growth factor beta 1 induced cell cycle arrest in keratinocytes.

Transforming growth factor beta 1 (TGF-beta 1) is known to inhibit epithelial cell growth by inducing a G1 cell cycle arrest. We have studied the effect of TGF-beta 1 on protein binding to a transcription factor E2F consensus element in extracts from early passage human keratinocytes (HFKs) and a permanent human keratinocyte cell line (HaCaT). Treatment of these cells with TGF-beta 1 resulted in the formation of a DNA binding complex between the pRb-related protein p130 and E2F. Formation of the E2F-p130 complex correlated with inhibition of cell cycle progression in G1 and suppression of the E2F-regulated cdc2 gene. While p130 mRNA and protein levels were not influenced by TGF-beta 1, the activity of cyclin-dependent kinase 2 (Cdk2) towards p130 in vitro was inhibited. The results identify p130 as a downstream target of TGF-beta 1 and a possible mediator of the G1 cell cycle arrest.

CDC2 Protein Kinase↗

PubMed1995

The role of immunoglobulin kappa elements in c-myc activation.

Burkitt's lymphoma cells are characterized by chromosomal translocations involving the proto-oncogene c-myc on chromosome 8 and one of the immunoglobulin gene loci on chromosome 2, 14 or 22. The translocated c-myc allele is transcriptionally activated, shows a preferential usage of promoter P1 over P2 (promoter shift) and lacks the ability to retain the transcription complex at the P2 promoter. In order to define the elements of the immunoglobulin kappa gene involved in deregulation of c-myc in a t(2;8) translocation, we designed constructs consisting of c-myc and different parts of the immunoglobulin kappa gene locus. Chromatin analysis of these stably transfected constructs revealed DNase I hypersensitive sites within the c-myc 5' region characteristic for an actively transcribed c-myc gene and three sites within the immunoglobulin kappa locus corresponding to the matrix attachment region, the intron and 3' enhancers, respectively. These three regulatory elements were necessary and sufficient for maximal c-myc activation and formation of the promoter shift. Kinetic nuclear run on experiments were performed to study the distribution of transcription complexes on c-myc exon 1 on constructs with and without the immunoglobulin kappa regulatory elements. The absence of a pausing polymerase complex at the c-myc P2 promoter could be demonstrated for constructs consisting of c-myc and the two kappa enhancers. Therefore the two enhancers are sufficient to relief the elongational block at the P2 promoter, however, the matrix attachment region is additionally required for maximal c-myc activation observed in Burkitt's lymphoma cells.

Base Sequence↗

PubMed1995

Changes in the living arrangements of older women: an international study.

This study analyzes trends in the percentage of older women living alone in 21 European and North American countries over the period of 1960-1992. The general pattern is one of substantial annual increases in the percentage of elderly women living alone. This trend is shown to result mainly from demographic changes, with little evidence of a role for economic variables. The analysis suggests a reversal of the current trend in coming years, as mothers of postwar baby booms reach old age.

Aged↗

PubMed1995

Mycobacterial pseudotumors of lymph node. A report of two cases diagnosed at the time of intraoperative consultation using touch imprint preparations.

OBJECTIVE: The purpose of this report is to emphasize the diagnostic utility of intraoperative touch imprint preparations in the evaluation of Mycobacterium avium-intracellulare-infected lymph node biopsy specimens obtained from human immunodeficiency virus-positive patients. PATIENTS: Two human immunodeficiency virus-positive men, 41 and 29 years of age, with marked lymphadenopathy clinically suspicious for malignant neoplasm. RESULTS: Intraoperative touch imprints of two lymph node biopsy specimens rapidly demonstrated the presence of numerous intracellular organisms in Mycobacterium avium-intracellulare-infected lymph nodes, including one case of mycobacterial spindle cell pseudotumor. CONCLUSIONS: Intraoperative touch imprint preparations are helpful in the evaluation of lymph node biopsy specimens obtained from human immunodeficiency virus-positive patients and allow rapid diagnosis of Mycobacterium avium-intracellulare infection.

Adult↗

PubMed1995

A case study on the use of multiple imputation.

Multiple imputation is a relatively new technique for dealing with missing values on items from survey data. Rather than deleting observations for which a value is missing, or assigning a single value to incomplete observations, one replaces each missing item with two or more values. Inferences then can be made with the complete data set. This paper presents an application of multiple imputation using the 1987-1988 National Survey of Families and Households. We impute several binary indicators of whether the respondent's elderly mother/mother-in-law is married. Descriptive statistics are then presented for the sample of adult children with an unmarried mother or mother-in-law.

Adult↗

PubMed1994

Role of c-myc in simian virus 40 large tumor antigen-induced DNA synthesis in quiescent 3T3-L1 mouse fibroblasts.

Stably transfected NIH 3T3-L1 mouse fibroblasts (L1 cells) expressing the simian virus 40 large tumor antigen (LTAg) maintain c-myc expression and proliferation in low serum, whereas cells expressing the mutant form LTAg-K1, defective in binding of the retinoblastoma suppressor gene product pRb, showed reduced levels of c-myc RNA and only background levels of DNA synthesis in low serum. The role of the c-Myc protein in LTAg-induced DNA synthesis was studied in microinjection experiments. Expression of LTAg induced cellular DNA synthesis in > 95% of microinjected serum-starved L1 cells, whereas the mutant LTAg-K1 could not induce DNA synthesis. Coexpression of dominant negative c-Myc or Max mutants with LTAg inhibited DNA synthesis, indicating that functional c-Myc is necessary for induction of DNA synthesis by LTAg. Expression of c-Myc induced programmed cell death (apoptosis) in serum-starved L1 cells. Coexpression of c-Myc with LTAg-K1 restored induction of DNA synthesis without apoptosis. Expression of a truncated LTAg, LTAg-(1-259), defective in binding of the tumor suppressor gene product p53, failed to prevent c-Myc-induced apoptosis. The data indicate that c-Myc can restore the ability of LTAg-K1 to induce DNA synthesis and that LTAg-K1 prevents c-Myc-induced apoptosis in serum-starved L1 cells by its interaction with p53.

3T3 Cells↗

PubMed1994

Activation of pausing RNA polymerases by nuclear run-on experiments.

The nuclear run-on transcription assay is the only approach to measure the transcriptional activity of a given gene in its genuine structural and regulatory cellular context. However, serious problems in the interpretation of results can arise from the artificial activation of paused RNA polymerases during the transcription reaction, leading to false results with regard to the level and mode of gene regulation in vivo. We have used the example of the human proto-oncogene c-myc, which has previously been reported to be regulated by premature termination of transcription, to describe the problems and pitfalls in the interpretation of nuclear run-on experiments. We show here that activation of paused, elongation-incompetent polymerases in nuclear run-on experiments produces a strong transcription signal on c-myc exon 1 in cells which do not express c-myc steady-state RNA.

Base Sequence↗