Phantom limbs still a ghostly phenomenon.
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Anesthesia, Epidural↗
Biomedical subjects
E Thompson
Publications and source records attributed to E Thompson.
Seroprevalence of human immunodeficiency virus among adolescent attendees of Mississippi sexually transmitted disease clinics: a rural epidemic.
Human immunodeficiency virus (HIV) infection among adolescents is causing increasing concern, and teenagers attending sexually transmitted disease (STD) clinics run a high risk of contracting it. To determine the status of HIV infection in a Mississippi adolescent population, we evaluated seroprevalence rates for adolescents attending Mississippi State Department of Health STD clinics from 1988 to 1990. During this 2-year period, 9855 adolescents (aged 13 to 20 years) attended STD clinics, and HIV antibody was confirmed in 39 (seroprevalence rate 4.0/1000; 95% confidence interval [CI] 2.7 to 5.2). Seropositive rates were almost equal for male and female subjects (4.1/1000 and 3.8/1000, respectively), suggesting predominantly heterosexual transmission. Rates among blacks were 3.5 times higher than among whites. Adolescents with HIV infection were identified throughout the state, irrespective of urban centers. Rates among the smallest counties (ie, population less than 25,000) were not significantly different from those of the largest counties (ie, population greater than 100,000). Mississippi's rank in the top 10 states for other STDs and the state's high teenage pregnancy rate make it an epicenter of the HIV epidemic among adolescents.
Adolescent↗
Linkage analysis of malignant melanoma with the chromosome 1 markers D1S47 and PND.
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Chromosomes, Human, Pair 1↗
Pleiotropic effects of antithrombin strand 1C substitution mutations.
Six different substitution mutations were identified in four different amino acid residues of antithrombin strand 1C and the polypeptide leading into strand 4B (F402S, F402C, F402L, A404T, N405K, and P407T), and are responsible for functional antithrombin deficiency in seven independently ascertained kindreds (Rosny, Torino, Maisons-Laffitte, Paris 3, La Rochelle, Budapest 5, and Oslo) affected by venous thromboembolic disease. In all seven families, variant antithrombins with heparin-binding abnormalities were detected by crossed immunoelectrophoresis, and in six of the kindreds there was a reduced antigen concentration of plasma antithrombin. Two of the variant antithrombins, Rosny and Torino, were purified by heparin-Sepharose and immunoaffinity chromatography, and shown to have greatly reduced heparin cofactor and progressive inhibitor activities in vitro. The defective interactions of these mutants with thrombin may result from proximity of s1C to the reactive site, while reduced circulating levels may be related to s1C proximity to highly conserved internal beta strands, which contain elements proposed to influence serpin turnover and intracellular degradation. In contrast, s1C is spatially distant to the positively charged surface which forms the heparin binding site of antithrombin; altered heparin binding properties of s1C variants may therefore reflect conformational linkage between the reactive site and heparin binding regions of the molecule. This work demonstrates that point mutations in and immediately adjacent to strand 1C have multiple, or pleiotropic, effects on this serpin, leading ultimately to failure of its regulatory function.
Adolescent↗
Expression of the human T cell receptor V beta repertoire.
We have used a sensitive assay, based on amplification of cDNA by the polymerase chain reaction, to determine in a variety of human tissues the relative levels of expression of the genes coding for each of the twenty families of human TcR V beta. We have determined the diversity of the expressed TcR V beta repertoire early in the development of the immune system. We have shown that the full TcR V beta repertoire is expressed early into the second trimester; the expressed repertoire is as diverse at this point, in both fetal thymus and spleen, as it is in mature thymus and peripheral blood lymphocytes. In addition the relative expression in the fetal thymus of each V beta gene is conserved to a large extent in the fetal spleen.
Adult↗
Ewing's sarcoma: local tumor control and patterns of failure following limited-volume radiation therapy.
Sixty children with localized osseous Ewing's sarcoma were treated between 1978 and 1988 with induction chemotherapy (cyclophosphamide, adriamycin), irradiation and/or surgery, and 10 months of maintenance chemotherapy (cyclophosphamide, adriamycin, dactinomycin, vincristine). Following induction chemotherapy, 43 patients received primary radiation therapy to limited radiation volumes defined by post-chemotherapy residual soft tissue tumor extension and initial osseous tumor extent. Irradiation was defined as low dose at 30-36 Gy (median 35 Gy) for 31 cases with objective response to induction chemotherapy and high dose at 50-60 Gy (median 50.4 Gy) for 12 patients with poor response to induction chemotherapy or with tumors greater than or equal to 8 cm. Overall event-free survival at 5 years is 59% and local tumor control is 68%. Initial failures have been local (12), simultaneous local and distant failures (7), and distant (6). In the surgical resection group, 14 patients had complete resection without radiation therapy, and 3 patients had microscopic residual plus 35-41 Gy; 100% local control has been maintained. In 43 patients with primary radiation therapy group, local tumor control is 58% (p = .004). Despite limited radiation volume, 18/19 local failures occurred centrally within the bone, well within the radiation volume. Imaging response to induction chemotherapy predicted local tumor control in the radiation therapy group: 62% with complete response/partial response versus 17% with no response/progressive disease (p less than 0.01). Local tumor control related strongly to primary tumor size in the radiation therapy group; among 31 cases receiving 35 Gy, local tumor control is 90% for lesions less than 8 cm versus 52% for tumors greater than or equal to 8 cm (p = .054). The central pattern of local failure in this experience suggests the effectiveness of limited radiation volume. The overall local tumor control rate following the tested dose level of 35 Gy appears to be inadequate, although results in selected cases with tumors less than 8 cm in greatest tumor dimension indicate potential efficacy in a yet limited experience.
Adolescent↗
Metastatic small cell tumor of bone with 'true' rosettes and glial fibrillary acidic protein positivity.
A 15-year-old black girl was admitted to St. Jude Children's Research Hospital with a lytic lesion involving the right fourth metacarpal bone with a solitary metastasis to the ipsilateral axillary lymph node. Histologic examination of both the primary lesion and metastasis revealed a primitive small round cell lesion. Abundant rosettes with central lumina were present in the metastasis. Immunohistochemical stains performed on sections of the metastasis were strongly positive for glial fibrillary acidic protein (GFAP) and negative for neuron-specific enolase (NSE), S-100 protein, and Leu-7. Electron microscopic examination of the metastasis revealed lumen formation with apical microvilli and juxtaluminal junctional complexes. This tumor exhibits features that are suggestive, but not definitive, of primitive ependymal differentiation and further expands the morphologic and immunophenotypic range of small round cell tumors of bone.
Adolescent↗
Antithrombin Glasgow II: alanine 382 to threonine mutation in the serpin P12 position, resulting in a substrate reaction with thrombin.
A female with recurrent thrombosis was found to have a functional abnormality of antithrombin, with a ratio of functional to immunological activity in plasma of approximately 50%. Crossed immunoelectrophoresis in the presence of heparin was normal, indicating an abnormality of the reactive site, rather than the heparin binding domain. Accordingly, the antithrombin was isolated by heparin-Sepharose chromatography: this produced a mixture of normal and variant antithrombin, as the patient was heterozygous for the abnormality. To remove the normal component, the antithrombin was passed through a column of thrombin-Sepharose. On sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), prior to its application to thrombin-Sepharose, the antithrombin migrated as a single band with identical mobility to that of normal antithrombin. After thrombin-Sepharose, the purified variant component was proteolysed, and migrated as two components, one with a reduced and one with enhanced mobility under non-reducing conditions. This demonstrated that the variant was unable to form stable inhibitor-thrombin complexes and was cleaved in a substrate reaction with thrombin. One site of cleavage was unambiguously ascertained to be the Arg 393-Ser 394 reactive site bond, by NH2 terminal sequencing of the cleaved variant antithrombin: 10 steps beginning at the P1' position, Ser-Leu-Asn-Pro-Asn-Arg,..., were clearly identified. The mutation responsible for this defect was studied by polymerase chain reaction (PCR) amplification of exon 6 of the antithrombin gene and direct sequencing of the amplified product. The presence of both a G and A in the first position of codon 382, identified the mutation GCA to ACA, which results in the substitution of Ala 382 to Thr. This is identical to that reported for antithrombin Hamilton (Devraj-Kizuk et al, 1988), although antithrombin gene polymorphism analysis suggests that the antithrombin Glasgow II mutation has arisen independently. We have recently shown (Caso et al, 1991) that mutation at a nearby position, Ala 384 to Pro, also transforms another variant, antithrombin Vicenza/Charleville, into a substrate for thrombin. The present results with antithrombin Glasgow II suggest that all the alanine residues at the base of the reactive site loop in positions P12-10 may be important for the formation of a stabilized inhibitor-thrombin complex.
Adult↗
Adenosine deaminase and thymocyte maturation.
The congenital absence of adenosine deaminase in humans results in severe combined immunodeficiency. To clarify the process whereby thymocytes are destroyed in the absence of adenosine deaminase activity, we induced a parallel condition in mice through the injection of an inhibitor of adenosine deaminase, deoxycoformycin. We have observed that deoxycoformycin, in addition to maintaining high levels of dATP in thymocytes, blocks the progression of thymocyte differentiation at two points. As a result of the first block, the cortex is depleted of immature cortical thymocytes while CD4+CD8+ thymocytes with functionally rearranged T-cell receptors survive. As a result of the second block, the CD4+CD8+ thymocytes are prevented from further differentiation to mature CD4+CD8- or CD4-CD8+ T lymphocytes and accumulate at the corticomedullar junction and in the medulla. These observations suggest that the maintenance of dNTP pools by adenosine deaminase is critical to at least two stages of thymocyte differentiation.
Adenosine Deaminase↗
Depletion of c-myc with specific antisense sequences reverses the transformed phenotype in ras oncogene-transformed NIH 3T3 cells.
ras oncogene-transformed NIH 3T3 cells expressing glucocorticoid-inducible antisense c-myc cDNA transcripts at levels sufficient to deplete c-myc protein lost their transformed morphology and the ability to grow in soft agar; their ability to form tumors in nude mice was also impaired. These changes were dependent on the continuous expression of the antisense sequences. No major effects on plating efficiencies, growth rates in monolayer culture, or immortalization were observed in the revertant cells, indicating that the observed effects were not a toxic consequence of c-myc protein depletion. Transfection with the same vector expressing c-myc in the sense orientation or other control vectors had no effect on transformation. These results suggest that a certain minimum level of expression of c-myc is required for the maintenance of ras transformation in NIH 3T3 cells.
Animals↗
Hemodialysis and heparin. Alternative methods of measuring heparin and of detecting activation of coagulation.
A bolus dose of heparin was administered pre-dialysis to patients (n = 6) undergoing regular maintenance hemodialysis with cuprophane flat plate and hollow fiber membranes. Blood samples were withdrawn at hourly internals for measurement of a) heparin and b) activation markers of coagulation, fibrinolysis and platelets. Two assay methods for heparin were employed; amidolytic assay of anti-factor Xa activity in plasma and a simple whole blood clotting time based upon factor Xa inhibition (Heptest). Results from these heparin assays correlated well with each other (r = 0.89) and both showed similar negative correlations (r = -0.72, amidolytic and r = -0.66, Heptest) with levels of a marker of fibrin clot formation, fibrinopeptide A (FPA). Large differences in levels of FPA were observed during dialysis with the two dialyzer types, when similar levels of heparin were present. Heparin levels declined from 1-5-h dialysis and were associated with rises in plasma levels of FPA, thrombin-antithrombin complex (TAT) and beta thromboglobulin (BTG), but not of D-dimer. Regression analysis revealed the best correlation was between FPA and TAT (r = 0.94), followed by FPA and BTG (r = 0.81). FPA and D-dimer exhibited significant, but lower (r = 0.42), correlation. TAT levels, like FPA levels, showed good correlation with heparin (r greater than 0.65). It is concluded that the Heptest assay may be a useful bedside measurement of heparin levels and the TAT assay may be a simplified means of evaluating coagulation system activation during dialysis.
Antithrombin III↗
Myeloid neoplasia in children treated for solid tumours.
Therapy-related myeloid neoplasia developed 14 to 189 months after diagnosis of the primary malignancy in 12 out of 3365 children treated for malignant solid tumours; 6 of the 12 were in their first complete remission. The 10-year cumulative incidence of myeloid neoplasia was 1.3% (95% Cl 0.5-3.6) for the 447 patients with Hodgkin's disease, 1.3% (0.4-4.3) for the 420 with non-Hodgkin lymphoma, and 1.2% (0.3-5.2) for the 440 with neuroblastoma. This complication appeared in 1 of 180 children with brain tumours and in none of the 1878 with other malignancies. Risk of therapy-related myeloid neoplasia in patients with Hodgkin's disease was associated with recurrence of the primary malignancy, a combination of radiotherapy and chemotherapy with alkylating agents, and age greater than or equal to 12 years at diagnosis of Hodgkin's disease. Of the 8 patients who underwent chromosomal analysis of neoplastic myeloid cells, 2 showed complete loss of chromosome 7 and 4 showed t(9;11) or t(8;21) with or without del(16)(q22). The 2 patients who had received an epipodophyllotoxin had an 11q23 abnormality. The risk of therapy-related myeloid neoplasia is low in children with malignant solid tumours.
Adolescent↗
Antithrombin Padua. I: Impaired heparin binding caused by an Arg47 to his (CGT to CAT) substitution.
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Amino Acid Sequence↗
Anterior temporal lobectomy for complex partial seizures: evaluation, results, and long-term follow-up in 100 cases.
We report evaluation and results in 100 patients who had undergone anterior temporal lobectomy for intractable complex partial seizures. Average follow-up was 9.0 years (range, 2 to 21 years). In the 2nd postoperative year, 63% were seizure free, 16% were significantly improved, and 21% were considered not significantly improved. Mean number of seizures in the last group was 27% of preoperative levels. Surgical results did not change significantly in subsequent postoperative years; good outcomes tended to persist over the longer term. We also examined the utility of continuous depth electrode monitoring in the evaluation of patients with independent bitemporal interictal epileptiform activity. Despite limited numbers of subjects in this category, there was a trend toward improved surgical outcome when such subjects were evaluated with depth electrodes.
Adolescent↗
Consistent linkage of dominantly inherited osteogenesis imperfecta to the type I collagen loci: COL1A1 and COL1A2.
The segregation of COL1A1 and COL1A2, the two genes which encode the chains of type I collagen, was analyzed in 38 dominant osteogenesis imperfecta (OI) pedigrees by using polymorphic markers within or close to the genes. This was done in order to estimate the consistency of linkage of OI genes to these two loci. None of the 38 pedigrees showed evidence of recombination between the OI gene and both collagen loci, suggesting that the frequency of unlinked loci in the population must be low. From these results, approximate 95% confidence limits for the proportion of families linked to the type I collagen genes can be set between .91 and 1.00. This is high enough to base prenatal diagnosis of dominantly inherited OI on linkage to these genes even in families which are too small for the linkage to be independently confirmed to high levels of significance. When phenotypic features were compared with the concordant collagen locus, all eight pedigrees with Sillence OI type IV segregated with COL1A2. On the other hand, Sillence OI type I segregated with both COL1A1 (17 pedigrees) and COL1A2 (7 pedigrees). The concordant locus was uncertain in the remaining six OI type I pedigrees. Of several other features, the presence or absence of presenile hearing loss was the best predictor of the mutant locus in OI type I families, with 13 of the 17 COL1A1 segregants and none of the 7 COL1A2 segregants showing this feature.
Chromosomes, Human, Pair 17↗
HIV testing in Mississippi: questions doctors ask.
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AIDS Serodiagnosis↗
Functional ovarian cysts in patients cured of ovarian neoplasms.
Twenty-seven patients with ovarian cancer underwent unilateral salpingo-oophorectomy and were followed for 12-215 months (mean 80) after completion of therapy. Of these, nine patients who received pelvic irradiation subsequently developed ovarian failure. Of the remaining 18 patients who maintained ovarian function, 13 (72%) developed a functional ovarian cyst during the follow-up period. Of these 13 patients, eight were observed until the functional cyst regressed, four were treated with oral contraceptives (OCs) to suppress ovarian function, and one underwent oophorectomy for a large corpus luteum cyst. We recommend that OC pills be considered for suppression of ovarian function in postmenarcheal girls after completion of therapy for ovarian neoplasms. Routine use of OCs may simplify the follow-up of these patients by preventing the formation of functional ovarian cysts. In postmenarcheal patients not treated with OCs, the finding of a unilocular ovarian cyst should be considered to represent a functional cyst, and a trial of OCs for 3 months may result in spontaneous regression. Persistent cysts must be operatively removed.
Adolescent↗
Joint estimation of recombination fractions and interference coefficients in multilocus linkage analysis.
Estimation of recombination fractions and interference coefficients is of importance in multilocus linkage analysis. With the development of molecular genetic technologies such as RFLP, multilocus data are readily available to researchers. Several methods have been developed to analyze such data, and each performs well under restrictive conditions. The present paper proposes a method based on a multiplicative model and maximum-likelihood estimation of recombination fractions and interference coefficients. The estimators are consistent regardless of the model assumptions and are efficient if the model is a good approximation. The estimators are tractable even when there are incomplete observations. Furthermore, the interference between nonadjacent chromosomal regions or those among three chromosomal regions can be modeled and tested by a simple Z-test. The proposed method was applied to linkage analysis of four-locus data obtained from Drosophila and that of seven-locus data obtained again from Drosophila. Reanalysis of the first example revealed that there is interference between chromosomal regions 2 and 3. Analysis of the second example suggested that there is triple interference as well as pairwise interference between nonadjacent chromosomal regions; the genetic interpretation of these findings remains to be developed.
Genetic Linkage↗