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S D Smith

Publications and source records attributed to S D Smith.

At least 181 records · Page 10Linked to original sources
PubMed1991

Evidence for major gene transmission of developmental dyslexia.

OBJECTIVE: --There is strong evidence that developmental dyslexia is both familial and heritable, but the mode of genetic transmission has remained unclear. In this article, we examine specific genetic hypotheses about the mode of transmission of developmental dyslexia by performing complex segregation analyses. DESIGN: --A family study method was applied, whereby the relatives of dyslexic probands were examined for dyslexia. The families studied represent four independently ascertained samples. SETTING: --The four samples of families were primarily from rural and suburban communities of Colorado, Washington State, and Iowa. PARTICIPANTS: --A total of 204 families and 1698 individuals in the four samples combined. MAIN OUTCOME MEASURES: --The complex segregation program, POINTER, was used to test competing genetic hypotheses of how a categorical trait (dyslexia) is transmitted in families. RESULTS: --The results were consistent with major locus transmission in three of four samples and with polygenic transmission in the fourth. In these three samples, the estimates of penetrance for the AA, Aa, and aa genotypes (where A is the abnormal allele) were, respectively, 1.000, 1.000, and 0.001 to 0.039 in males, and 0.560 to 1.000, 0.550 to 0.897, and 0.000 in females. The estimated gene frequency of the major locus was between 3% and 5%. CONCLUSIONS: --Sex-influenced, additive, or dominant transmission occurs in a significant proportion of dyslexic families. Other evidence indicates, however, that dyslexia is etiologically heterogeneous and that there is genetic heterogeneity even among families selected for apparent dominant transmission. Thus, while no single major locus may account for all of dyslexia, it is important to pursue potential major loci for dyslexia using linkage techniques.

Adult↗
PubMed1991

TAN-1, the human homolog of the Drosophila notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms.

Previously we described joining of DNA in the beta T cell receptor gene to DNA of an uncharacterized locus in a t(7;9)(q34;q34.3) chromosomal translocation from a case of human T lymphoblastic leukemia (T-ALL). We now show that the locus on chromosome 9 contains a gene highly homologous to the Drosophila gene Notch. Transcripts of the human gene, for which we propose the name TAN-1, and its murine counterpart are present in many normal human fetal and adult mouse tissues, but are most abundant in lymphoid tissues. In t(7;9)(q34;q34.3) translocations from three cases of T-ALL, the breakpoints occur within 100 bp of an intron in TAN-1, resulting in truncation of TAN-1 transcripts. These observations suggest that TAN-1 may be important for normal lymphocyte function and that alteration of TAN-1 may play a role in the pathogenesis of some T cell neoplasms.

Amino Acid Sequence↗
PubMed1991

Improved treatment results in boys with overt testicular relapse during or shortly after initial therapy for acute lymphoblastic leukemia. A Pediatric Oncology group study.

Boys with acute lymphoblastic leukemia (ALL) who have overt testicular relapse (OTR) during initial continuation chemotherapy or within 6 months thereafter have poor outcomes, with long-term survival similar to patients with marrow relapse during treatment. In April 1983, the Pediatric Oncology Group (POG) adopted for these patients an intensive treatment protocol (POG 8303) consisting of a four-drug systemic reinduction (prednisone, vincristine, daunorubicin, and asparaginase), a brief intensive consolidation phase with teniposide and cytarabine, and a 2-year program of continuation chemotherapy with weekly rotating drug pairs (vincristine/cyclophosphamide and teniposide/cytarabine) with or without (by randomization) four-drug reinforcement pulses every 16 weeks. Bilateral testicular radiation (2600 cGy) was administered during reinduction, and intrathecal chemoprophylaxis was given every 4 to 6 weeks. Among 38 eligible study patients with OTR, 5 had prior or concominant extramedullary relapse in other sites. The median duration of complete remission before OTR was 27 months (range, 10 to 42 months). All 38 patients achieved clinical remission after reinduction. Three patients withdrew while in remission, 22 had another relapse (12 marrow, 5 central nervous system (CNS), 2 testicular, 1 retroperitoneal, 1 prostate, and 1 eye), and 13 (34%) remain in complete remission from 32+ to 74+ months after OTR (median, 53+ months). Eighteen patients had their therapy electively discontinued, and five relapses occurred thereafter. These results are superior to those observed in patients with first marrow relapse treated with the same protocol. Approximately one third of patients with OTR treated with POG protocol 8303 exhibit prolonged second remissions with the potential for cure.

Adolescent↗
PubMed1991

The effect of E coli virulence on bacterial translocation and systemic sepsis in the neonatal rabbit model.

In the surgical neonate, three factors that promote bacterial translocation and systemic infection are: (1) intestinal bacterial colonization and overgrowth; (2) compromised host defenses; and (3) disruption of the mucosal epithelial barrier. The newborn rabbit provides an excellent model to study these factors. Like the human, there is early closure of the gut mucosa to macromolecules, and nutrition can be maintained by breast or formula feeding. This study examines translocation and systemic sepsis after colonization with virulent K1 and avirulent K100 strains of Escherichia coli. New Zealand white rabbit pups (2 to 5 days old) were studied. The gastrointestinal tracts of 12 were colonized with K1 E coli; 14 were colonized with K100 E coli; 12 control animals were not inoculated. Mesenteric lymph node (MLN), liver, spleen, and colon homogenate were cultured 72 hours postinoculation. No bacteria were isolated from the colons of all but one control animal. Translocation or systemic sepsis did not occur. Translocation to the MLN was significantly increased (P less than .03) in K1 (50%) and K100 (36%) groups compared with controls (0%). Translocation to liver and spleen (systemic sepsis) was significantly increased (P less than .03) in K1 animals (67%) compared with K100 (0%) or controls (0%). Colonization by both strains of E coli led to translocation to the MLN, but only K1 E coli caused systemic sepsis. This suggests that although colonization by E coli in the newborn leads to translocation to the MLN, progression to systemic sepsis is the result of characteristics of the bacteria and/or neonatal host responses.

Animals↗
PubMed1991

Characterization of neonatal multisystem organ failure in the surgical newborn.

With advances in critical care, multisystem organ failure (MSOF) has replaced single organ failure as the major cause of death in adult patients. The purpose of this report is to characterize neonatal MSOF (NMSOF) in the surgical newborn. The records of 84 infants who died during a 5-year period in the surgical neonatal intensive care unit were reviewed. There was sufficient information available in 10 newborns to characterize the NMSOF syndrome. Criteria for renal, hepatic, microvascular, pulmonary, cardiac, and hematologic failure were developed. The sequence of organ failure was determined by calculating the number of days prior to death when these criteria were first noted. Systemic infections were recorded. The sequence of organ failure was as follows: microvascular (edema) 17 +/- 10 days, renal 14 +/- 7 days, hepatic 13 +/- 5 days, hematologic 8 +/- 4 days, pulmonary 5 +/- 2 days, and cardiac 3 +/- 2 days. Adult respiratory distress syndrome (ARDS) was absent. The 10 infants showed both culture-positive sepsis (8) and culture-negative sepsis (2). This is the first report to characterize NMSOF in newborn surgical patients. The earliest findings were edema, followed by renal and hepatic failure. In contrast to adult MSOF, anasarca is a prominent early finding, pulmonary failure develops late, and classic ARDS is absent.

Acute Disease↗
PubMed1991

Osteoporosis in late life: does health locus of control affect psychosocial adaptation?

Osteoporosis, a metabolic bone disease most prevalent in older adults, is a major public health problem. Although management of osteoporosis through diet, exercise, and medication has improved, little is known about the psychosocial consequences of this disabling disease. In an attempt to identify patient characteristics that would provide physicians with insight into appropriate management styles for older osteoporotics, we assessed 103 patients with osteoporosis for their health locus of control (HLOC) orientation. We examined the relationship between HLOC and patient outcomes after participation in the Duke University Preventive and Therapeutic Program for Osteoporosis (DUPATPO) to determine whether HLOC was associated with functioning after program participation. More specifically, we asked whether internal or external HLOC was associated with decreases in depression, psychiatric symptoms, and stress symptoms, or with increases in self-esteem, exercise, and disease knowledge. We have shown in our earlier work (Gold et al, J Am Geriatr Soc 1989; 37:417) that program participation is associated with improved functioning in older adults. We now asked whether knowledge of a patient's HLOC would help predict these improvements. A comparison group (ie, older osteoporotics who did not participate in DUPATPO) was also assessed for HLOC to examine the possible association between HLOC and health behaviors regardless of the DUPATPO intervention. Our findings indicate that HLOC provided little useful information regarding patient outcomes. Although improvements were seen in the mental health of program participants, no association between these improvements and HLOC could be found.

Adaptation, Psychological↗
PubMed1991

Human leukemic T and B lymphoblasts produce insulin-like growth factor binding proteins 2 and 4.

The production of insulin-like growth factors and insulin-like growth factor binding proteins by twelve human leukemic lymphoblast cell lines was evaluated by radioimmunoassay, affinity cross-linking, ligand blot, and immunoprecipitation of conditioned media. In all cell lines, detectable IGF-I and IGF-II levels were less than 0.1 micrograms/l and less than 0.3 micrograms/l, respectively. IGF binding proteins were identified in 6/12 of the lymphoblast cell lines studied. A pair of IGF binding proteins at 31 and 33 kD, immunoprecipitated with an antibody recognizing IGF binding protein 2 but not by an IGF binding protein 3 antibody, was produced by both T and B cells. A 24 kD IGF binding protein, presumably IGF binding protein 4, since it was not recognized by the antibodies for IGF binding proteins 1, 2, and 3, was produced by B cell precursor cells and faintly by one T cell line. These IGF binding proteins were not altered by deglycosylation. Neither IGF binding protein 1 nor IGF binding protein 3 was identified in any of the conditioned media. We speculate that local production of IGF binding proteins 2 and 4 regulates access of the IGFs to lymphoblasts and to hematopoietic precursors in general.

B-Lymphocytes↗
PubMed1991

Physiological responses of newborn Bos indicus and Bos indicus x Bos taurus calves after exposure to cold.

Brahman (n = 9) and 1/2 Simmental x 1/4 Brahman x 1/4 Hereford (n = 11) calves were utilized to determine the influence of exposure to cold on the physiology of the neonate. All calves were removed from their dams within 20 min of birth and prior to suckling. Calves were assigned randomly within breed to either a warm (W; 31 degrees C) or cold (C; 4 degrees C) environmental treatment group. Jugular blood samples were collected via indwelling catheters at 20-min intervals for 180 min. At 100 to 120 min of sampling, all calves were given 1.2 liters of colostrum from their dams via stomach tube. At 120 min, C calves were placed in the W environment. Calf vigor score (CVS) and rectal temperature were determined at each time blood was collected. Serum or plasma was analyzed for glucose (GLU), lactate (LAC), blood urea nitrogen (BUN), hemoglobin (HEM), triglyceride (TRG), triiodothyronine (T3), thyroxine (T4), insulin (INS), cortisol (CORT) and nonesterified fatty acid (NEFA) concentration. Rectal temperature was lower (P less than .01) in C Brahman than in W Brahman and C or W crossbred calves. Crossbred calves had higher (P less than .01) CVS than Brahman calves. Calves in W had lower (P less than .01) GLU than C calves. Brahman calves had higher GLU, LAC, BUN, TRG, T3, T4 and CORT (P less than .05) than crossbred calves. The C Brahman calves had the highest (P less than .05) TRG, CORT, T3 and T4 of all groups. Concentration of NEFA were higher (P less than .01) in C than in W calves.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Pancreatic ductal abnormalities in children.

From 1979 to 1990, 33 children required operative treatment for pancreatitis. Causes included ductal abnormalities (12 children), trauma (10 children), idiopathic (four children), gallstones (three children), drug-induced (three children), and tumor (one child). This study reviews the characteristics and outcome of the 12 children with ductal abnormalities. Symptoms were present up to 9 years or less before diagnosis, with two patients undergoing negative appendectomies. At diagnosis, amylase levels averaged 612 IU/L and lipase, 4761 IU/L. Preoperative studies included ultrasonography (11 children), endoscopic retrograde cholangiopancreatography (nine children), and computerized tomography (six children). Intraoperative cholangiopancreatography was performed in nine patients and was essential in four to diagnosis their anomaly. Patients were categorized into those with a common channel (three children), ampullary stenosis (two children), ductal fusion error (one child), or combinations (six children). Operations included sphincteroplasty (seven patients), pancreaticobiliary separation (six patients), pancreatic duct enterostomy (three patients), and distal pancreatectomy (one patient). Three patients required more than one procedure to repair the combination anomalies. Symptoms resolved immediately in nine patients. Two patients had delayed resolution, with one patient requiring the addition of somatostatin. One patient was lost to follow-up. Recurrent or protracted pancreatitis, without obvious cause, requires expeditious endoscopic retrograde cholangiopancreatography and/or intraoperative cholangiopancreatography. Operative therapy should be tailored to ductal anatomy and will resolve symptoms in most children.

Abdomen↗
PubMed1990

Specific recognition of human leukemic cells by allogeneic T cells: II. Evidence for HLA-D restricted determinants on leukemic cells that are crossreactive with determinants present on unrelated nonleukemic cells.

Transplantation of immunocompetent cells present within allogeneic bone marrow has been associated with the elimination of residual host leukemia, both in animal tumor models and in patients receiving marrow transplants for leukemia. This observation has been called the "graft-versus-leukemia effect." We have attempted to study this phenomenon in vitro by characterizing the cytolytic response of T cells from normal donors after in vitro activation with allogeneic leukemic cells. As expected, most T cells that react against an allogeneic patient's leukemic cells recognize their foreign HLA antigens and lyse the patient's nonleukemic remission lymphoid cells. In addition, we have shown that a small fraction of the T cells recognize and lyse foreign leukemic targets without lysis of nonmalignant remission targets from the same leukemic patient. These T cells have been isolated and characterized as CD3+, CD4+ cells expressing the alpha/beta T cell receptor (TCR). Their lysis appears to reflect specific antigen recognition mediated via the CD3-TCR complex and interactions involving the CD4 receptor. Some of these "leukemic specific" T cell lines, which are restricted by HLA class II molecules, can also lyse occasional nonleukemic cells from certain unrelated donors. This recognition appears to involve crossreactive determinants shared by the leukemic cells and the unrelated allogeneic nonleukemic cells. These specific interactions may represent an in vitro model of the graft-versus-leukemia effect.

Antigens↗
PubMed1990

Interaction of RNA polymerase I transcription factors with a promoter in the nontranscribed spacer of rat ribosomal DNA.

The spacer promoter of the rat rDNA repeat consists of two functional domains: a core (proximal) element that is sufficient for transcription in vitro, and an upstream (distal) promoter element that increases the efficiency of transcription. Two of the transcription factors that interact with the 45S promoter also interact with the spacer promoter. Rat SL-1, is required for transcription of the spacer promoter by heterologous extracts, e.g. human, and rat SF-1 is required for efficient transcription in vitro. Order-of-addition experiments demonstrated that the preinitiation complex formed by these factors on the spacer promoter is not as stable as the complex formed on the 45S promoter. DNase 1 footprinting experiments demonstrated binding sites for rat SL-1 and SF-1 on the distal element of the spacer promoter. The topology of the domains of the spacer promoter may explain both the reduced stability of the preinitiation complex formed on that promoter and the lower efficiency of transcription of that promoter when compared to the 45S promoter.

Animals↗
PubMed1990

Chromosomal translocation t(1;19) results in synthesis of a homeobox fusion mRNA that codes for a potential chimeric transcription factor.

The gene (E2A) for enhancer binding transcription factors E12 and E47 maps to the t(1;19) chromosomal translocation breakpoint in pre-B cell leukemias. Altered E2A transcripts lacking sequences coding for the helix-loop-helix DNA binding motif were detected in several t(1;19)-carrying cell lines. Fusion cDNAs that crossed the t(1;19) breakpoint were cloned and shown to code for an 85 kd protein consisting of the amino-terminal two-thirds of E2A fused to a chromosome 1-derived protein. The fusion protein has the features of a chimeric transcription factor in which the DNA binding domain of E2A is replaced by the putative DNA binding domain of a homeoprotein from chromosome 1 for which the name Prl (pre-B cell leukemia) is proposed. Identical E2A-prl mRNA junctions were detected by PCR in three t(1;19)-carrying cell lines, indicating that the fusion transcripts and predicted chimeric protein are a consistent feature of this translocation.

Amino Acid Sequence↗
PubMed1990

Molecular analysis of the t(1;19) breakpoint cluster region in pre-B cell acute lymphoblastic leukemias.

The t(1;19) chromosomal translocation in acute lymphoblastic pre-B cell leukemias involves the gene E2A for helix-loop-helix (HLH) proteins E12 and E47, ubiquitous transcriptional proteins implicated in the regulation of various lymphoid and nonlymphoid genes. To characterize the molecular features of the t(1;19)(q23;p13) translocation, we molecularly cloned breakpoint DNA from t(1;19)-carrying pre-B cell leukemias. In all cases, breakpoints on chromosome 19 occurred within 2 kb of each other in a single intron of the E2A gene. This clustered arrangement resulted in specific truncation of the E2A gene and transcript, with loss of sequences encoding the basic DNA-binding and HLH dimerization motifs from the derivative 19 chromosome. In contrast, breakpoints on chromosome 1 were distributed over a large region and could not be linked to exonic sequences of the PBX1 gene, although identical chromosome 1 sequences are joined to E2A sequences in 1;19 fusion transcripts. These data show that the 1;19 translocation consistently results in exchange of 3' exons encoding the HLH motifs of E2A with DNA from chromosome 1 to form a fusion gene on the derivative 19 chromosome.

Blotting, Southern↗
PubMed1990

Mapping of translocation breakpoints on the short arm of chromosome 19 in acute leukemias by in situ hybridization.

Non-random translocation involving the short arm of chromosome 19 are frequently observed in acute leukemias. Recent studies have shown that the 19p13 genes E2A and LYLl, both of which encode helix-loop-helix proteins, lie at two different translocation breakpoints in acute lymphoblastic leukemias (ALL). The E2A gene is involved by the t(1;19)(q23;p13) in acute pre-B-cell leukemias and the LYL1 gene is structurally altered by a t(7;19)(q34;p13) in T-cell ALL. To assess the role of these genes in other leukemia-associated translocations we mapped their locations with respect to the t(11;19)(q23;p13) and t(4;19)(q21;p13) translocation breakpoints carried by T-ALL cell lines SUP-T13 and SUP-T8a, respectively. In situ hybridization studies indicated that the E2A and LYL1 genes are physically distinct from the t(4;19) and t(11;19) breakpoints. Using these and other 19p13 translocation breakpoints as landmarks, we established a partial physical map of 19p: 19pter-E2A-INSR-LYL1-[t(4;19)]-19cen. These data should help guide molecular studies to further characterize 19p13 breakpoints and mapping of genes in this chromosomal region.

Acute Disease↗
PubMed1990

The hidden mortality in surgically treated necrotizing enterocolitis: fungal sepsis.

From 1979 to 1986, 82 infants underwent surgical treatment for necrotizing enterocolitis (NEC), with 36 deaths. The records of 30 of the 36 infants who died were available for review. Fungal colonization and sepsis, the sites of infection, and timing of diagnosis and therapy were determined. Sixteen of 30 (53%) neonates had no evidence of fungus. Six (20%) were colonized with Candida species. Eight (27%) had fungal sepsis, with two of these eight found only at necropsy. Positive fungal blood cultures were a late finding. In only four of the six patients with positive blood cultures were the results known in time to initiate treatment with amphotericin B. Two of these four babies received less than 2 days of amphotericin B treatment prior to death. Fungal sepsis is a significant lethal factor in the surgical mortality of NEC. Vigorous efforts at earlier diagnosis are mandatory.

Enterocolitis, Pseudomembranous↗
PubMed1990

Selective bowel decontamination results in gram-positive translocation.

UNLABELLED: Colonization by enteric gram-negative bacteria with subsequent translocation is believed to be a major mechanism for infection in the critically ill patient. Selective bowel decontamination (SBD) has been used to control gram-negative infections by eliminating these potentially pathogenic bacteria while preserving anaerobic and other less pathogenic organisms. Infection with gram-positive organisms and anaerobes in two multivisceral transplant patients during SBD led us to investigate the effect of SBD on gut colonization and translocation. METHODS: Twenty-four rats received enteral polymixin E, tobramycin, amphotericin B, and parenteral cefotaxime for 7 days (PTA + CEF); 23 received parenteral cefotaxime alone (CEF), 19 received the enteral antibiotics alone (PTA), 21 controls received no antibiotics. Cecal homogenates, mesenteric lymph node (MLN), liver, and spleen were cultured. RESULTS: Only 8% of the PTA + CEF group had gram-negative bacteria in cecal culture vs 52% CEF, 84% PTA, and 100% in controls. Log Enterococcal colony counts were higher in the PTA + CEF group (8.0 + 0.9) vs controls (5.4 + 0.4) P less than 0.01. Translocation of Enterococcus to the MLN was significantly increased in the PTA + CEF group (67%) vs controls (0%) P less than 0.01. SBD effectively eliminates gram-negative organisms from the gut in the rat model. Overgrowth and translocation of Enterococcus suggests that infection with gram-positive organisms may be a limitation of SBD.

Animals↗