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Biomedical subjects

T Fanning

Publications and source records attributed to T Fanning.

17 recordsLinked to original sources

A family of repetitive DNA sequences in Old World primates.

A dispersed family of repetitive DNA sequences that is amplified in Old World primates has been characterized. The sequences are present in about 250-350 copies in humans, found on all chromosomes, and some are at least 1 kb in size. Within the core repeat is a 178-bp region that is moderately-to-highly conserved. A representative sequence exhibited strong promoter activity when placed in front of a promoterless gene and transfected into human cells. This promoter activity has been localized to a 138-bp region of the repeat that is about 150 bp downstream of the 178-bp conserved region. Transcripts of the sequences were not detected in six human breast epithelial and teratocarcinoma cell lines. Based upon the work of Pavelitz et al. [Pavelitz, T., Rusche, L., Matera, A.G., Scharf, J.M., Weiner, A.M., 1995. EMBO J. 14, 169-177], the sequence appears to be related to the LTR of an HERV-K class human endogenous retrovirus.

Animals

Differential methylation of human LINE-1 retrotransposons in malignant cells.

Long interspersed element-1 (LINE-1) retrotransposons from Homo sapiens (L1Hs) are not expressed in normal somatic cells. In malignant cells, there is a direct correlation between the hypomethylation of 5' L1Hs sequences and the presence of L1Hs proteins, suggesting that elements with hypomethylated 5' ends are transcriptionally active. Sequences flanking the 5' ends of hypomethylated L1Hs elements were isolated from the T-47D breast cancer cell line by inverse-PCR and cloning. These flanker clones served as probes for analyzing the loci harboring the hypomethylated L1Hs elements. Sequencing demonstrated that the flankers have no homology with one another and do not appear to contain common short motifs that might serve as recognition sites for regulatory factors. The hypomethylated L1Hs elements are located on many chromosomes, although three of twelve are on chromosome 15. Southern blotting indicates that certain elements are hypomethylated in numerous cell lines, and that elements that are hypomethylated in malignant germ cells comprise a different subset of elements than those that are hypomethylated in non-germ cell malignancies. These results suggest that the subset of L1Hs elements that is hypomethylated in malignant cells is not simply a random collection of L1Hs elements.

Chromosome Mapping

Prenatal care of HIV-infected women: analysis of a large New York State cohort.

We examined the effect of methadone treatment, duration of Medicaid enrollment during pregnancy, and other maternal characteristics on receipt of prenatal care by 2,254 women infected with human immunodeficiency virus (HIV) delivering a singleton in New York state from 1985 through 1990. Data were obtained from the New York State Medicaid HIV/AIDS Research Data Base and vital statistics records. Adequacy of the number of prenatal visits reported by the mother on vital statistics records was assessed with use of the Kessner Index, which adjusts for gestational age at delivery. Too few visits were reported by 65% of the study population. Illicit drug users had higher odds of having too few visits [1.64, 95% confidence interval (CI) 1.24-2.17] than methadone-treated women but the odds were similar for non-drug users and methadone-treated women (0.79, 95% CI 0.60-1.25). Women with brief Medicaid enrollment (< or = 25% of pregnancy) had 45% higher odds of having too few visits than did longer enrollees. Treatment for drug addiction and longer Medicaid enrollment during pregnancy may offer important interventions to increase prenatal care of HIV-infected women. Approaches to increase prenatal care of HIV-infected women are especially important given trials showing a reduction in vertical transmission from zidovudine treatment during pregnancy.

Adolescent

Recently amplified satellite DNA in Callithrix argentata (primates, Platyrrhini).

A satellite DNA has been cloned from the neotropical primate Callithrix argentata and designated CarB. The presence of the satellite was assayed in New and Old World primates by blot hybridization: CarB is highly amplified in the genomes of all three species belonging to the C. argentata species group (C. argentata, C. emiliae, C. humeralifer), but is either absent, or present in only minor amounts, in other primates, including the closely related species, C. jacchus. A completely sequenced CarB monomeric unit was 1528 bp in length and mapped to the telomeric C-band-positive regions of many C. argentata species group chromosomes. Sequence data from eight CarB clones indicated an average difference of 3.5% when base substitutions alone were counted. The hybridization and sequence data suggest that this satellite underwent a period of amplification and dispersal in the genome of a recent ancestor of the C. argentata species group.

Animals

Alpha satellite DNA in neotropical primates (Platyrrhini).

The alpha satellite DNA of Old World (catarrhine) primates usually consists of similar, but not identical, ca. 170 bp sequences repeated tandemly hundreds to thousands of times. The 170 bp monomeric repeats are components of higher-order repeats, many of which are chromosome specific. Alpha satellites are found exclusively in centromeric regions where they appear to play a role in centromere function. We have found that alpha satellite DNA in neotropical (New World; platyrrhine) primates is very similar to its Old World counterpart: it consists of divergent ca. 170 bp subsequences that are arranged in tandem arrays with a ca. 340 bp periodicity. New and Old World alpha satellites share about 64% sequence identity overall, and contain several short sequence motifs that appear to be highly conserved. One exception to the tandemly arrayed 340 bp motif has been found: the major alpha satellite array in Chiropotes satanas (black bearded saki) has a 539 bp repeat unit that consists of a 338 bp dimer together with a duplication of 33 bp of the first monomeric unit and 168 bp of the second monomeric unit.

Animals

AIDS specialist versus generalist ambulatory care for advanced HIV infection and impact on hospital use.

We examined patterns of ambulatory care in the year before diagnosis of acquired immune deficiency syndrome (AIDS) for 5,720 persons infected with human immunodeficiency virus (HIV) who were continuously enrolled in the New York State Medicaid program and diagnosed in 1984-90. For 3,175 persons followed > or = 6 months after AIDS, we also examined the change between the year before AIDS diagnosis and the 6 months afterward in the predominant provider who was seen most frequently and at least twice. Approximately 75% of the population had a predominant provider identified. Of this group, 43% of the patients had a generalist as their predominant provider before AIDS diagnosis, falling to only 25% after diagnosis. The proportion with an AIDS specialist predominant provider increased from 22% before AIDS diagnosis to 39% afterward (P < 0.001). Patients with a generalist predominant provider before AIDS diagnosis had higher odds of switching providers and of hospitalization after AIDS diagnosis than patients with an AIDS specialist predominant provider. If generalists are to be encouraged to manage patients with advanced HIV disease, a better understanding of factors contributing to these outcomes is needed.

Acquired Immunodeficiency Syndrome

Health care delivery, zidovudine use, and survival of women and men with AIDS.

The aim of this study was to define predictors of survival for women and men after AIDS diagnosis. We examined health care delivery and drug therapy in the year before AIDS diagnosis for continuously enrolled New York State Medicaid beneficiaries with AIDS in 1988-1990. We examined the association of these factors with survival after AIDS diagnosis. Of 1,077 women and 1,871 men, 60% of both gender groups were drug users. In both risk groups, women had more outpatient visits than men but were equally likely to visit an AIDS specialist. In those who were not drug users, men were twice as likely as women to receive either zidovudine or Pneumocystis carinii pneumonia prophylaxis. No difference appeared among drug users. Survival after AIDS diagnosis was similar by gender for those who were not drug users (RR = 1.09; 95% CI = 0.90-1.33). In drug users, women had a slightly lower risk of death than men (RR = 0.84; 95% CI = 0.72-0.98). Risk of death after AIDS diagnosis was higher for persons starting zidovudine earlier in both risk groups. Among drug users, women received more ambulatory care and survived slightly longer than men. Among those who were not drug users, survival was similar by gender even after adjusting for differences in care.

Acquired Immunodeficiency Syndrome

Survival experience of 789 children with the acquired immunodeficiency syndrome.

To define predictors of survival we studied longitudinal histories of 789 New York State Medicaid-enrolled children diagnosed with acquired immunodeficiency syndrome (AIDS) from 1983 to 1989 and followed through 1990. Median survival times for 3 severity groups of AIDS-defining conditions were 66, 48 and 9 months. In a proportional hazards model, the relative risk of death for the most vs. least severe group was 3.33 (95% confidence interval, 2.53, 4.37) and the relative risk for children < 6 months old at diagnosis vs. older children was 1.81 (95% confidence interval, 1.41, 2.34). We increased our ability to predict death by using a 4-category severity index that assesses both the AIDS-defining diagnosis and clinical complications within 3 months of diagnosis (relative risk, 5.27; 95% confidence interval, 3.16, 8.78 for most vs. least severe). These analyses offer new clinical severity measures and reveal that, regardless of the AIDS-defining diagnosis, children with AIDS who are < 6 months old have a poor prognosis.

Acquired Immunodeficiency Syndrome

The limits of marginal economic incentives in the Medicaid program: concerns and cautions.

In January 1985, New York State implemented legislation that allowed for a 30 percent increase in Medicaid fees for physicians providing primary care services. This was intended to increase their levels of participation. Yet the outcome was not as expected. In upstate New York, the number of physicians participating in Medicaid each month actually declined; in New York City, the monthly rate of increase in participating physicians, which was part of the overall sharp rise in all licensed physicians, underwent a decline. Furthermore, utilization measures suggest that "procedural upgrading" might have become a problem in New York City. These results suggest that a marginal increase in New York State's low Medicaid fees will not have a positive effect on physician participation levels.

Fees, Medical

The role of gene rearrangements for antigen receptors in the diagnosis of lymphoma obtained by fine-needle aspiration. A study of 63 cases with concomitant immunophenotyping.

To assess the efficacy of performing genotyping in addition to immunophenotyping as an adjunct to cytologic diagnosis, 63 consecutive patients with fine-needle aspirates of lymphoproliferative lesions who had concurrent immunophenotyping and genotyping performed on fine-needle aspirate cell suspensions were studied. Thirty-nine of 63 specimens (62%) that appeared to contain non-Hodgkin's lymphoma and that proved to be of B-cell lineage by genotyping were accurately phenotyped and shown to be monotypic for immunoglobulin light chains by cell suspension immunocytochemistry. Genotyping facilitated lineage assignment and/or confirmed clonality in 17 of 63 specimens (27%) that were difficult to determine based on morphologic data. These include cases of atypical lymphoid proliferations with polyclonal or inconclusive markers (n = 6), peripheral T-cell lymphoma (n = 3), extracutaneous mycosis fungoides (n = 1), lymphoblastic lymphoma (n = 4), null cell lymphoma (n = 1), and specimens with equivocal or technically unsatisfactory markers (n = 2). Based on these results, it is proposed that genotyping for lineage assignment and/or clonality be performed to include cases of atypical lymphoid proliferations, T-cell malignant neoplasms, lymphoid malignant neoplasms with equivocal markers, and differentiation of lymphoid from nonlymphoid neoplasms. Genotyping by antigen-receptor gene rearrangement appears to be redundant in cases with mature B-cell phenotypes that demonstrate monoclonality by immunophenotyping.

Adult

The AIDS-defining diagnosis and subsequent complications: a survival-based severity index.

To define a survival-based severity measure for AIDS, we convened a panel of AIDS experts who identified factors influencing AIDS prognosis and estimated the impact of prognostic factors on survival time. The resulting conceptual model included 19 AIDS-defining conditions and 80 subsequent AIDS-related complications. This model was tested on longitudinal disease histories of 3,937 AIDS patients in the New York State Medicaid Program diagnosed between 1983 and 1986 and followed through 1988. The initial AIDS diagnosis and complications within 3 months of AIDS onset were identified from coded diagnoses recorded on inpatient and outpatient claims. Three AIDS-defining diagnosis groups were created; survival times from least to most severe group were 25, 10, and 7 months. To determine the influence of subsequent complications on risk of death, the survival times associated with combinations of defining diagnosis groups and four severity levels of subsequent complications were determined. Median survival ranged from 43 months for the least severe defining diagnosis group without early complications to 12 months for the group with severe defining diagnoses and serious complications. The matrix of AIDS-defining diagnoses and complications was divided into four severity categories with significantly different survival curves. This severity measure uses longitudinal data commonly available to clinicians and researchers to create distinct AIDS prognostic categories.

Acquired Immunodeficiency Syndrome

Fine-needle aspiration cytology and flow cytometry of intracystic papillary carcinoma of breast.

To define criteria for cytologic diagnosis of intracystic papillary carcinoma (ICPC), the authors retrospectively reviewed the fine-needle aspiration (FNA) cytologic specimens of eight cases of histologically proven ICPC of breast. The patients were five black and three white women, 56-87 years of age. The FNA specimen was cyst fluid in four cases (bloody in three, clear in one). All the aspirates showed cellular smears with small and large clusters of cells with papillary and/or cribriform configurations and numerous single epithelial cells. The cells were cuboidal to columnar with minimal atypia. ICPC was suggested by FNA in each case, and all the patients underwent surgical excision or mastectomy. Flow cytometry, performed on fresh FNA specimen in one case and on paraffin-embedded surgical tissue in all eight cases, showed seven tumors to be aneuploid and one to be diploid. The authors contend that ICPCs of breast have distinct cytomorphologic features that can be recognized by FNA. Because ICPC may present in cyst fluid, either bloody or clear, all breast cyst fluids from postmenopausal women should be examined cytologically. Flow cytometric demonstration of an aneuploid population may assist in confirming malignancy in this lesion.

Aged

The LINE-1 DNA sequences in four mammalian orders predict proteins that conserve homologies to retrovirus proteins.

Recent work suggests that one or more members of the highly repeated LINE-1 (L1) DNA family found in all mammals may encode one or more proteins. Here we report the sequence of a portion of an L1 cloned from the domestic cat (Felis catus). These data permit comparison of the L1 sequences in four mammalian orders (Carnivore, Lagomorph, Rodent and Primate) and the comparison supports the suggested coding potential. In two separate, noncontiguous regions in the carboxy terminal half of the proteins predicted from the DNA sequences, there are several strongly conserved segments. In one region, these share homology with known or suspected reverse transcriptases, as described by others in rodents and primates. In the second region, closer to the carboxy terminus, the strongly conserved segments are over 90% homologous among the four orders. One of the latter segments is cysteine rich and resembles the putative metal binding domains of nucleic acid binding proteins, including those of TFIIIA and retroviruses.

Amino Acid Sequence

Diagnostic electron microscopy using fine needle aspiration biopsies.

Electron microscopy can be a valuable aid to light microscopy in the interpretation of fine needle aspiration biopsies of tumors, but considerable care in procuring and processing the specimen is necessary to recover the tumor cells and avoid altering their fine structure. Fixation followed by filtration through a cloth screen is recommended. Experience with this technique is briefly reviewed.

Adult

Expandable biliary endoprosthesis: an experimental study.

Expandable stents constructed of stainless-steel wire were inserted in the extrahepatic bile ducts of five animals to determine the effect of the endoprosthesis on the ductal wall. The stents were left in place 4-23 weeks, at which time the bile ducts were inspected. The bile ducts remained patent in all animals. Relatively mild reactive inflammatory changes observed in the wall of the bile ducts were more pronounced in animals with stents in place for the longest periods. A relatively small-caliber catheter (9 French) was necessary for the introduction of the stent, which acquired a much larger diameter once it was released from the catheter. This study suggests that expandable wire stents could be safely used to relieve biliary obstruction.

Animals