PubMed Health⌕ Search

Biomedical subjects

S D Smith

Publications and source records attributed to S D Smith.

At least 19 recordsLinked to original sources
PubMed1992

Electromagnetic gating in ion channels.

There have been many attempts to develop a theoretical explanation of the phenomena of electromagnetic field interactions with biological systems. None of the reported efforts have been entirely successful in accounting for the observed experimental results, in particular with respect to the reports of interactions between extremely low frequency (ELF) magnetic fields and biological systems at ion cyclotron resonance frequencies. The approach used in this paper starts with the Lorentz force equation, but use is made of cylindrical co-ordinates and cylindrical boundary conditions in an attempt to more closely model the walls of an ion channel. The equations of motion of an ion that result from this approach suggest that the inside shape of the channel plus the ELF magnetic fields at specific frequencies and amplitudes could act as a gate to control the movement of the ion across the cell membrane.

Animals↗
PubMed1992

Fusion of the leucine zipper gene HLF to the E2A gene in human acute B-lineage leukemia.

A t(17;19) chromosomal translocation in early B-lineage acute leukemia was shown to result in chimeric transcripts that contain sequences from the E2A basic helix-loop-helix transcription factor gene on chromosome 19, fused to sequences from a previously unidentified gene (HLF) on chromosome 17 that encodes a hepatic leukemia factor. The chimeric protein consisted of the amino-terminal transactivation domain of E2A linked to the carboxyl-terminal basic region-leucine zipper domain of HLF. HLF was normally expressed in liver and kidney, but not in lymphoid cells, and was found to be closely related to the leucine zipper-containing transcription factors DBP (albumin D-box binding protein) and TEF (thyrotroph embryonic factor), which regulate developmental stage-specific gene expression.

Adenovirus Early Proteins↗
PubMed1992

Analysis of the rat ribosomal DNA promoter: characterization of linker-scanning mutants and of the binding of UBF.

To investigate the mechanism of transcription of the rat ribosomal DNA (rDNA) promoter, a series of 23 linker-scanning mutants were constructed and assayed in transfected CHO cells and with cell-free extracts. With minor variation, the results of the in vitro and in vivo assays paralleled one another. For example, these assays demonstrated that the mutagenesis of bases from -133 to -124, and those from -106 to -101 of the rDNA promoter significantly inhibited transcription both in vivo and in vitro. Both of these sites lie within the upstream promoter element (UPE) of the rDNA promoter. Several constructs, in particular one that mutated the bases between -49 and -45, were better promoters in vivo than the wild-type promoter. DNAse footprinting experiments with purified UBF, an RNA polymerase I transcription factor, demonstrated the importance of the bases between -106 and -101 for the binding of that factor, providing a positive correlation between the transcription experiments and the binding of UBF to the rDNA promoter.

Animals↗
PubMed1992

Analysis of the phosphorylation, DNA-binding and dimerization properties of the RNA polymerase I transcription factors UBF1 and UBF2.

The phosphorylation, DNA-binding and dimerization properties of both forms of the RNA polymerase I transcription factor UBF were studied and compared. Tryptic peptide maps of in vivo 32P-labeled UBF contained four phospho-peptides. Two of these peptides are predicted to derive from the serine-rich, carboxyl-terminal of UBF. This region contains nine consensus phosphorylation sites for casein kinase II, and is one of the regions phosphorylated in vitro by casein kinase II. Analysis of the DNA-binding properties of recombinant forms of UBF1 and UBF2 by Southwestern blots revealed: (1) a role for the NH2-terminal 102 amino acid domain of UBF1/UBF2 in DNA-binding; (2) the importance of the bases from -106 to -101 of the rat ribosomal DNA promoter for the binding of UBF; and (3) functional differences between UBF1 and UBF2. Glutaraldehyde cross-linking and overlay assays using recombinant forms of UBF1 and UBF2 demonstrated that the molecules can form both homodimers and heterodimers. These assays also demonstrated that the NH2-terminal 102 amino acids of UBF plays a significant role in dimerization and that other domains contribute to dimerization. The dimerization properties of recombinant forms of UBF1 and UBF2 were different, suggesting that the HMG box 2 of UBF1, which is partially deleted in UBF2, also contributes to UBF dimerization.

Animals↗
PubMed1992

Differential phosphorylation and localization of the transcription factor UBF in vivo in response to serum deprivation. In vitro dephosphorylation of UBF reduces its transactivation properties.

We have analyzed the expression, phosphorylation, and localization of the ribosomal DNA transcription factors UBF1 and UBF2 in Chinese hamster ovary cells in response to serum deprivation. In vivo labeling experiments demonstrate that UBF1 and UBF2 are phosphoproteins. Phosphoamino acid analysis of the in vivo labeled proteins demonstrate that UBF is phosphorylated on serine residues. Following serum deprivation there is no alteration in the cellular levels of UBF1 and UBF2 as determined by Western blotting, but there is an 80% reduction in the level of phosphorylation of UBF compared with logarithmically growing cells. Following serum deprivation there is a redistribution of UBF between the nucleolus, the nucleus, and the cytoplasm. Phosphatase-treated UBF demonstrated a reduced ability to rescue transcription by RNA polymerase I from the rDNA spacer promoter in vitro. These findings suggest that phosphorylation of UBF is a prerequisite for transactivation of RNA polymerase I.

Alkaline Phosphatase↗
PubMed1992

Catheter sepsis in short-bowel syndrome.

Catheter sepsis with catheter removal is an important problem in patients with short-bowel syndrome. We determined the incidence of catheter sepsis and the catheter salvage rate in 20 pediatric patients with short-bowel syndrome. To evaluate the intestine as a source and translocation as the pathophysiologic mechanism for catheter sepsis, we identified the sepsis organisms, compared them with the fecal flora, and used mesenteric lymph node cultures to document translocation. The incidence of catheter sepsis was significantly higher in patients with short-bowel syndrome than in patients without short-bowel syndrome (7.8 vs 1.3 per 1000 catheter days). Overall catheter salvage was 42% and was highest in gram-negative sepsis (71%). Enteric organisms were responsible for 62% of cases of catheter sepsis in patients with short-bowel syndrome vs 12% in patients without short-bowel syndrome. Anaerobes were strikingly absent in 25 of 28 stool cultures. The sepsis organism was identified in the fecal flora in 19 of 28 cases. The dominant fecal organism or yeast was the septic organism in 12 of these 19 cases and was isolated in three of four mesenteric lymph node cultures. Our findings support translocation as a mechanism in catheter sepsis in patients with short-bowel syndrome.

Anti-Bacterial Agents↗
PubMed1992

Impedance response characteristics of the primate Mucaca mulatta exposed to seated whole-body gz vibration.

A mathematical model was used to quantify and describe the variability in the mechanical impedance response of the Rhesus monkey subjected to vibrations in the range 3-20 Hz at 0.5 g peak acceleration. Due to the similarities in response, a two-mass, one-degree-of-freedom (DOF) model was selected and the associated mechanical parameters determined using a nonlinear least-squares optimization program. For the six tests conducted on each of the four subjects, appreciable parameter variations were observed within a subject; however, the majority of the mean parameter values among different subjects and among the repeated tests on the population were within +/- 1 S.D. of each other. Significant differences were observed in the stiffness coefficient and the total mass among different subjects, and in the mass ratio (between inert and sprung masses) among the repeated tests. Variations in the profile shapes following resonance were described and limited by changes in the mass ratio and the damping factor. Higher mass ratios (greater than 1.0) were associated with lower damping factors (less than 0.50). The impedance response beyond resonance approached the response described by the impedance of the inert mass and the damper elements of the model combined in parallel, and supported the assumption that the lower torso was rigidly attached to the seat. Physically, the reactive force produced by the upper torso increasingly diminished following resonance, due to the load transmission/attenuation characteristics of the spinal structures at 0.5 g peak acceleration. The impedance measured at the seat becomes dominated by the transmitted damping force associated with the spine and the force generated by the rigid lower-torso mass.

Acceleration↗
PubMed1992

Unique characteristics of the neonatal intestinal mucosal barrier.

The purpose of this study was to compare the newborn and weanling intestinal mucosa to determine differences in: (1) the electrophysiologic characteristics of the mucosal barrier; (2) the effects of glutamine supplementation on these physiological characteristics; and (3) transmucosal bacterial passage. The Ussing chamber was used to study ileal mucosa from newborn (1 to 4 days old) and weanling (21 days old) piglets. After the seromuscularis was stripped off the bowel wall, the mucosa was mounted in the chamber and perfused with Hanks Balanced Salt Solution (HBSS) or HBSS + 20 mmol/L of glutamine. Following initial stabilization, potential difference (PD) and resistance (R) were measured at 30-minute intervals for 2 hours. Transmucosal bacterial passage was measured by quantitative cultures of the mucosal and serosal reservoirs obtained 2 hours after adding 10(8) E coli C-25 to the mucosal reservoir. Six groups of membranes were studied: (1) newborn and HBSS; (2) weanling and HBSS; (3) newborn and HBSS + glutamine; (4) weanling and HBSS + glutamine; (5) newborn - HBSS + glutamine + E coli; and (6) weanling - HBSS + glutamine + E coli. Newborn ileal mucosa had significantly lower PD and R compared with weanling at all time points. Glutamine led to a significant increase in PD in both newborn and weanling. Newborn mucosa had a significantly increased incidence of transmucosal bacterial passage (4/7) compared with weanling (0/10). These findings suggest that: (1) newborn mucosal barrier has uniquely different electrophysiologic characteristics; (2) glutamine improves the metabolic activity as measured by PD in both newborn and weanling; and (3) the newborn mucosal barrier allows increased transmucosal passage of bacteria.

Animals↗
PubMed1992

Mucosal glutamine utilization after small-bowel transplantation: an electrophysiologic study.

A short course of FK 506 after small bowel transplantation averts rejection in the rat and achieves indefinite survival of the recipient whose nutritional status is dependent on the function of the intestinal graft. Ex vivo electrophysiologic studies using the Ussing Cell were conducted to delineate functional competence of the graft by evaluating mucosal ion transport and glutamine utilization. Orthotopic small-bowel transplantation was performed in Lewis (LEW) rats as recipients of either Brown-Norway (BN) allografts or LEW syngeneic grafts. Allograft recipients received FK 506 either as a short course (2 mg/kg on Day 0-4 after transplantation) or continuously (2 mg/kg Day 0-4, then 0.5 mg/kg weekly). Ileal mucosa was harvested from small bowel grafts 9 and 60 days after transplantation and mounted in the Ussing Cell containing Hanks' balanced salt solution with/without L-glutamine (20 mM). Transmembrane potential difference (PD), which represents mucosal active ion transport, and mucosal resistance, an index of membrane integrity, were recorded. Nine days after transplantation, mucosal PD was the same in the ileum from syngeneic grafts, allografts treated with FK 506 and normal LEW and BN rats, and the addition of glutamine increased PD equally in all groups. In comparison, PD was markedly decreased in allografts undergoing rejection, and the glutamine response was blunted. Sixty days after transplantation, mucosal PD was reduced in allografts treated with a short course of FK 506, but normal in allografts receiving continuous immunosuppression with FK 506 and in syngeneic grafts. A decrease of mucosal resistance was not a feature of rejection nor a sequel of limited FK 506 therapy. Our data indicate that allograft rejection results in a significant decrease in mucosal PD and a poor response to glutamine. Control of rejection by FK 506 preserves normal electrophysiologic responses of the allograft mucosa.

Animals↗
PubMed1992

Reading disability, immune disorders and non-right-handedness: twin and family studies of their relations.

Geschwind and colleagues discussed associations among learning disorders, immune disorders and non-right-handedness. In this study, we examined the associations between reading disability (RD) and both immune disorders (ID) and non-right-handedness (NRH) in family and twin samples (total N = 1731 cases) identified through an RD proband. We also conducted co-segregation analyses to ascertain the degree to which NRH, ID and RD were biologically related. There was little evidence for an overall association between RD and NRH. There was not convergent evidence across all four samples for an association between RD and ID, although we did find an association between RD and ID in two of four samples. Nor was there strong support for a subtype where RD and NRH, or RD and ID, co-segregate in families. These data suggest that the associations postulated by Geschwind and colleagues are not robust in RD samples, although we cannot completely rule out the possibility of an RD plus ID subtype.

Abortion, Spontaneous↗
PubMed1992

Treatment of occult or late overt testicular relapse in children with acute lymphoblastic leukemia: a Pediatric Oncology Group study.

PURPOSE: The Pediatric Oncology Group (POG) designed a randomized two-arm protocol (8304) to improve the survival of children with acute lymphoblastic leukemia (ALL) who experience an isolated testicular relapse and to evaluate the efficacy of teniposide (VM-26) and doxorubicin as intensification agents during second remission. The outcome and toxicity observed in 80 patients with isolated testicular leukemia treated on POG 8304 are presented. PATIENTS AND METHODS: The following are common features of POG 8304: (1) remission reinduction therapy with vincristine, prednisone, and doxorubicin; (2) bilateral testicular irradiation (2,600 cGy) during reinduction therapy; (3) CNS prophylaxis with intrathecal hydrocortisone, methotrexate (MTX), and cytarabine (Ara-C); and (4) continuation therapy (for 80 weeks) with alternating 6-week cycles of oral mercaptopurine (6-MP)/MTX and intravenous vincristine and cyclophosphamide. Treatment differences consisted of pulses (administered every 7 weeks) of either prednisone and doxorubicin (arm 1) or VM-26 and Ara-C (arm 2) during continuation therapy and a 4-week late intensification phase with either vincristine, prednisone, and doxorubicin (arm 1) or VM-26 and Ara-C (arm 2). RESULTS: Fifty-five boys with ALL had isolated microscopic testicular leukemia detected by an elective biopsy at completion of initial treatment, and 25 had a late (greater than or equal to 6 months off-therapy) isolated overt testicular relapse. All patients with overt testicular leukemia attained a second clinical remission, and no patient with microscopic testicular leukemia progressed during reinduction. Of 42 patients on arm 1, 11 have relapsed compared with 18 of 38 patients on arm 2 (log-rank analysis, P = .22), indicating no significant difference between an anthracycline and an epipodophyllotoxin-Ara-C combination in the treatment of testicular leukemia. The overall 4-year event-free survival (EFS) among boys with occult testicular relapse was 53% +/- 8%. Age greater than 10 years at initial diagnosis, a WBC count greater than 50,000/microL at diagnosis, and black race were associated with a worse outcome. The 4-year EFS for boys with a late overt testicular relapse was 84% +/- 10%, and these patients fared significantly better than patients with occult disease (P = .007). CONCLUSION: The treatment approach reported here can secure a prolonged second remission in many patients with occult or late overt testicular leukemia.

Adolescent↗
PubMed1992

Hallux abductus interphalangeus. Etiology, x-ray evaluation and treatment. 1975.

This paper discusses the normal adult values of the fibular deviation of the distal phalanx of the great toe. Occurrence of this deviation at birth is a normal finding and an increase can be expected during periods of active growth within the foot. This developmental increase is dependent upon transverse plane stability at the metatarsophalangeal joint. Preoperative procedures and postoperative reviews are discussed.

Female↗
PubMed1992

Mitogenic effects of human recombinant insulin on B-cell precursor acute lymphoblastic leukemia cells.

Insulin and the insulin-like growth factors (IGF-I, IGF-II) constitute a family of peptides capable of stimulating diverse cellular responses, including cell proliferation. In order to determine the effects of these peptides on malignant cells, we analyzed the expression and function of insulin, IGF-I, and IGF-II receptors on B-cell precursor acute lymphoblastic leukemia (BCP ALL) cell lines, utilizing competitive binding, affinity crosslinking, and cell proliferation assays. The BCP ALL cells bound to each peptide with mean specific binding for 125I-insulin, 125I-IGF-I, and 125I-IGF-II of 19.6%, 7.1%, and 4.3% of radioligand added, respectively. Competitive binding to intact cells demonstrated that 125I-IGF-I was displaced by IGF-I = IGF-II >> insulin, 125I-IGF-II was displaced by IGF-II > insulin = IGF-I, and 125I-insulin was displaced by insulin >> IGF-II > IGF-I. These data were remarkable for the potency of IGF-II displacement of 125I-IGF-I and 125I-insulin. Affinity crosslinking of radioligands to SUP-B2 cell membranes demonstrated the high affinity insulin and IGF-I (type 1 IGF) receptors. IGF binding proteins were also present in BCP ALL cell membrane preparations. In the cell proliferation studies, insulin stimulated a 50-130% increase in leukemic cell growth with a half-maximal concentration of 0.1-3.0 ng/ml in three BCP ALL cell lines. The proliferative response to insulin was blocked by the addition of an insulin receptor antibody. However, no response was observed with IGF-I, and IGF-II was only weakly mitogenic with a proliferative response noted at 100 ng/ml. Thus, while BCP ALL cells possess receptors for insulin and IGF-I, only the insulin receptor mediated a proliferative response.

Burkitt Lymphoma↗
PubMed1992

Coculture of bovine demiembryos prior to freezing.

Pregnancy rates after transfer of frozen/thawed bisected embryos, demiembryos, have until now been very low. In the present study it was attempted to improve the freezability rate of demiembryos by culturing them on a monolayer of bovine oviduct epithelial cells (BOEC) prior to freezing. The cultured frozen/thawed demiembryos showed a lower developmental rate than intact embryos. The pregnancy rate (23%) following transfer was not different from the pregnancy rate after transfer of unfrozen demiembryos (26%). The calving rate (4%), however, was significantly lower than the calving rate after transfer of fresh demiembryos (23%). Although the overall pregnancy rate achieved in this study was low, it can be concluded that a co-culture period upon BOEC prior to freezing does not improve the viability of frozen demiembryos.

Animals↗
PubMed1992

Blastomere content of cultured/frozen bovine demiembryos.

The purpose of the study was to evaluate whether a period of co-culture with bovine oviduct epithelial cells (BOEC) could improve the tolerance of bisected bovine embryos to freezing and thawing. Day 6 embryos were bisected and the resulting demiembryos were stained with Hoechst 33342 and cell counts were made by counting intact blastomere nuclei. Of these, 11 were stained as freshly manufactured demiembryos, 25 after co-culture for 24 h with BOEC and 37 stained after 24 h co-culture and freezing and thawing. The staining revealed, that there was no significant difference in cell count of demiembryos that were stained immediately after bisection, compared to those, that were co-cultured for a 24 h period. Also, the co-cultured/frozen/thawed demiembryos had a significant decrease in cell numbers compared to the non-frozen demiembryos. We conclude, that a 24 h period of co-culture with BOEC does not result in appreciable cellular proliferation in demiembryos and therefore instead of improving the survival of frozen/thawed demiembryos by giving them opportunity to multiply their cell number and thus make them more resistant to cell damage, rather compromised the viability of cryopreserved demiembryos.

Animals↗
PubMed1991

Identification of a gene, MLL, that spans the breakpoint in 11q23 translocations associated with human leukemias.

Recurring chromosomal translocations involving chromosome 11, band q23, have been observed in acute lymphoid leukemias and especially in acute myeloid leukemias. We recently showed that breakpoints in four 11q23 translocations, t(4;11)(q21;q23), t(6;11)(q27;q23), t(9;11)(p22;q23), and t(11;19)(q23;p13.3), were contained within a yeast artificial chromosome clone bearing the CD3D and CD3G gene loci. We have identified within the CD3 yeast artificial chromosome a transcription unit that spans the breakpoint junctions of the 4;11, 9;11, and 11;19 translocations, and we describe two other, related transcripts that are upregulated in the RS4;11 cell line. We have named this gene MLL (myeloid/lymphoid, or mixed-lineage, leukemia.

Adult↗