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Biomedical subjects

D L Williams

Publications and source records attributed to D L Williams.

At least 307 records · Page 17Linked to original sources
PubMed1985

Left ventricular volume determination using single-photon emission computed tomography.

A new method for measuring left ventricular (LV) volume based on gated single-photon emission computed tomography (SPECT) is described. Preliminary phantom studies showed an excellent correlation between SPECT and observed volumes (r = 0.99, standard error of the estimate [SEE] = 4.9 ml). SPECT was performed 24 hours after biplane contrast LV angiography in 36 patients. Transaxial blood pool tomograms were reconstructed by filtered back projection and reoriented to views orthogonal to the cardiac axes. Volume was calculated from serial short-axis tomograms by determining the base, apex and lateral borders of the LV blood pool, ascertaining the number of pixels in this volume and multiplying by the known volume of a pixel. Gated SPECT volumes were compared with contrast angiographic volumes. At end-systole, r = 0.96 and SEE = 12 ml; at end-diastole, r = 0.81 and SEE = 27 ml. For ejection fraction, r = 0.85 and SEE = 0.06. To test interobserver variation in processing, count data from 5 patients were processed twice (r = 0.98, SEE = 8.3 ml). There is an excellent correlation between SPECT and contrast angiographic volumes at end-systole; at end-diastole the relation is good. SPECT requires no arbitrary background correction, allows systematic isolation of the left ventricle from other overlapping cardiac chambers and requires no geometric assumptions for volume determination. It has promise as a direct method for measuring LV volume in a minimally invasive manner.

Adult↗
PubMed1985

Quantitation of apolipoprotein E mRNA in the liver and peripheral tissues of nonhuman primates.

A sensitive DNA-excess solution hybridization assay was used to quantitate apo-E mRNA in the liver and peripheral tissues of two nonhuman primates, Macaca fascicularis and Cercopithecus aethiops. When expressed on the basis of total RNA, apo-E mRNA values for M. fascicularis adrenal, brain, testis, and spleen ranged from 17-52% of the liver value. Apo-E mRNA values for mesenteric lymph node, kidney, thymus, and skeletal muscle were 1-5% of the liver value. When expressed on a cellular basis, apo-E mRNA was most abundant in the liver at approximately 1200 molecules/cell. Peripheral tissues showed a continuous range of apo-E mRNA from 1.5 molecules/cell in the thymus up to 350 molecules/cell in the brain. Similar results were obtained with peripheral tissues from C. aethiops in which case apo-E mRNA also was found in skin, lung, skeletal muscle, small intestine, and vascular tissues such as heart, aorta, and brachial artery. Calculation of the total apo-E mRNA/organ showed that most of the apo-E mRNA was present in the liver. However, summation of apo-E mRNA in peripheral tissues indicated that 20-40% of total body apo-E mRNA was extrahepatic. This results indicates that apo-E made in peripheral tissues may play a quantitatively important role in cholesterol metabolism since peripheral tissues have the potential to contribute a significant fraction of plasma apo-E.

Adrenal Glands↗
PubMed1985

Apolipoprotein E synthesis in peripheral tissues of nonhuman primates.

The tissue distribution of apolipoprotein (apo) E synthesis in the cynomolgus monkey, Macaca fascicularis, was determined via short-term organ culture with radiolabeled amino acid. Tissue extracts were reacted with antiserum to apo-E, and immunoprecipitates were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Newly synthesized apo-E was detected in liver, adrenal, testis, lung, spleen, mesenteric lymph node, and kidney. Peripheral and hepatic apo-E showed the same electrophoretic mobility. High resolution two-dimensional gel analysis showed that newly synthesized apo-E exists in two major isoforms in each tissue examined. Comparison of isoform patterns and mixing experiments showed that newly synthesized apo-E isoforms have identical charge properties in each tissue examined. These data indicate that numerous peripheral tissues synthesize apo-E that is indistinguishable from liver apo-E by the criteria tested. Measurements of relative synthetic capacities illustrate that apo-E is a moderately abundant protein product of a variety of peripheral tissues although quantitative differences in apo-E synthesis occur. Apo-E mRNA from cynomolgus monkey liver and human Hep G2 cells co-migrated with an electrophoretic mobility corresponding to approximately 1200 nucleotides. Apo-E mRNA from liver, brain, thymus, kidney, testis, lymph node, and spleen was the same size. Primer extension analysis yielded a cDNA product representing complete copying of the 5' untranslated region of human Hep G2 apo-E mRNA. A cDNA of identical size was produced with cynomolgus monkey apo-E mRNA from liver, spleen, brain, lymph node, kidney, lung, and thymus. These data suggest that transcription of the apo-E gene is initiated at or near the same site in each tissue examined.

Adrenal Cortex↗
PubMed1985

Experience-dependent recovery of cognitive functioning in young alcoholics.

Spontaneous recovery of some cognitive functioning in alcoholics after drinking has ceased has been convincingly demonstrated, but there have been no demonstrations of recovery that occurs primarily due to exposure of the alcoholic to specific environmental events. In the present study two groups of alcoholics began a 3-week series of tests sensitive to alcoholic cognitive dysfunction at different time lags after drinking ceased (1 week vs. at least 3 weeks). Each group received five administrations each of three tests. On two of the measures, comparisons between the initial testings administered at least three weeks apart revealed the expected pattern of improvement concommitant with the passage of time. On the Halstead-Reitan Trailmaking Test (Part B), initial test scores were equivalent, showing no time-dependent recovery. Instead, performance improved solely as a function of repeated task administration, thus demonstrating "experience-dependent" recovery. Initial levels of impairment and the extent of recovery were established using two non-alcoholic control groups. Since evidence has accrued that alcoholics' treatment outcome may relate to neuropsychological status, experience-dependent rehabilitation of cognitive functioning may improve success rates in alcoholism treatment.

Adult↗
PubMed1985

Changes in the H-1 histone complement during myogenesis. II. Regulation by differential coupling of H-1 variant mRNA accumulation to DNA replication.

We have shown that changes in proportions of the four chicken H-1's during in vitro myogenesis are primarily the result of differential coupling of their synthesis to DNA replication (see the previous paper). We show here that the four major chicken H-1's are encoded by distinct mRNAs which specify primary amino acid sequence variants. Accumulation of the H-1-variant mRNAs is coupled to DNA replication to different extents. The level of mRNA encoding H-1c (the H-1 variant that increases relative to the other H-1's in nondividing muscle cells) is completely uncoupled. In contrast, the level of mRNAs encoding H-1's a, b, and d (which have levels that decrease in nondividing muscle cells) are more tightly coupled. Polyadenylation is not involved in uncoupling H-1c mRNA accumulation from DNA replication.

Amino Acid Sequence↗
PubMed1985

Periodic acid-Schiff stain in childhood acute lymphoblastic leukemia: lack of independent prognostic value.

The authors reviewed 250 consecutive children with ALL to determine if the periodic acid-Schiff (PAS) score was a useful, independent predictor of time to failure. PAS stains were scored from 0 to 400 and divided into low- and high-score groups using a variance-ratio test (F test) to optimize any effect of PAS on prognosis. Although the effect of PAS score considered alone approached significance for time to failure, the PAS score lost all significance when the patients were divided into standard-risk and high-risk groups on the basis of peripheral white count, central nervous system involvement, mediastinal mass, or E-rosette positivity at diagnosis. A Cox regression analysis was performed on a subgroup of 198 patients for whom cytogenetic studies were also available. The PAS score again approached the level of significance when considered alone but was of no significance after the effects of peripheral white count, pseudodiploidy, mediastinal mass, and E-rosette positivity were removed. The authors conclude that the PAS stain has no independent prognostic significance in childhood ALL.

Adolescent↗
PubMed1985

Prognostic importance of blast cell DNA content in childhood acute lymphoblastic leukemia.

Using flow cytometric techniques, we determined the pretreatment distribution of DNA content in propidium iodide-stained leukemic blasts from 205 children with "standard-risk" acute lymphoblastic leukemia (ALL). Risk assignment was based on an initial WBC count less than 100 X 10(9)/L, no thymic mass, no meningeal leukemia, and lymphoblasts lacking sheep erythrocyte receptors or surface immunoglobulin. A single aneuploid leukemic line was detected in 74 cases (36.1%): 70 hyperdiploid and four hypodiploid. For hyperdiploid cases, the DNA index (DI, or ratio of the DNA content of leukemic v normal G0/G1 cells) ranged from 1.06 to 2.0 (median, 1.20). A secondary leukemic line with hyperdiploid cellular DNA content was identified in 21 cases with diploid primary lines. Children whose primary leukemic line showed a DI greater than or equal to 1.16 (n = 57) had significantly better responses to treatment than did those with either a diploid DI (n = 130; P = .002) or values in the range of 1.01 to 1.15 (n = 14; P = .001). The relative risk of failure for hyperdiploid cases with DI greater than or equal to 1.16, corresponding to greater than or equal to 53 chromosomes, was one-third that of the other two groups. Treatment responses of patients with both diploid and hyperdiploid lines were identical to those associated with single diploid lines, but significantly worse than those associated with single hyperdiploid lines with DI greater than or equal to 1.16 (P = .016). The most favorable prognostic variables selected by a Cox proportional hazards model were: DI greater than or equal to 1.16 (P = .001), white race (P = .022), WBC less than or equal to 25 X 10(9)/L (P = .032), age between 2 and 9 years (P = .075), and hemoglobin less than 7.0 g/dL (P = .094). DNA index greater than or equal to 1.16 retained its significant prognostic impact even after adjustment for other variables (P = .001). With the combination of DI greater than or equal to 1.16 and WBC less than or equal to 25 X 10(9)/L, one can identify a group of children with ALL who have a low probability of relapse when treated with current therapy. If they remain disease-free after longer follow-up, it may be advisable to treat them with less intensive, hence less toxic, chemotherapy than patients with higher WBC counts or lower DI values.

Antigens, Neoplasm↗
PubMed1985

Serial cell culture and cytogenetic studies of marrow cells from a patient with monosomy 7 syndrome.

Serial bone marrow cell culture studies, with cytogenetic characterization, were performed in an 18-month-old boy with monosomy 7 syndrome--a condition that usually converts to nonlymphoblastic leukemia. Over a 12-month course, his marrow demonstrated: decreased colony formation and increased cluster formation in vitro with disease progression (consistent with preleukemia); persistence of only the monosomy 7 karyotype in direct marrow studies; and in contrast, proliferation of both 46,XY and monosomy 7 cells in in vitro marrow cultures. The findings indicate that certain dormant marrow cell populations may be expressed under in vitro culture conditions and suggest the need for determining factors which would allow their expression in vivo.

Bone Marrow↗
PubMed1984

Comparison of effects of smooth and skeletal muscle tropomyosins on interactions of actin and myosin subfragment 1.

The ATPase activity of acto-myosin subfragment 1 (S-1) was measured in the presence of smooth and skeletal muscle tropomyosins over a wide range of ionic strengths (20-120 mM). In contrast to the 60% inhibitory effect caused by skeletal muscle tropomyosin at all ionic strengths, the effect of smooth muscle tropomyosin was found to be dependent on ionic strength. At low ionic strength (20 mM), smooth muscle tropomyosin inhibits the ATPase activity by 60%, while at high ionic strength (120 mM), it potentiates the ATPase activity 3-fold. All of these ATPase activities were measured at very low ratios of S-1 to actin, under conditions at which a 4-fold increase in S-1 concentration did not change the specific activity of the tropomyosin-acto.S-1 ATPase. Therefore, the potentiation of the ATPase activity by smooth muscle tropomyosin at high ionic strength cannot be explained by bound S-1 heads cooperatively turning on the tropomyosin-actin complex. To determine whether the fully potentiated rates are different in the presence of smooth muscle and skeletal muscle tropomyosins, S-1 which was extensively modified by N-ethylmaleimide was added to the ATPase assay to attain high ratios of S-1 to actin. The results showed that, under all conditions, the fully potentiated rates are the same for both tropomyosins.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗
PubMed1984

Independent developmental programs for two estrogen-regulated genes.

Measurement of hepatic apolipoprotein II and vitellogenin II messenger RNA during chicken embryogenesis showed that these genes acquire estrogen responsiveness at different stages of development. Sensitive solution hybridization assays with excess complementary DNA showed that apolipoprotein II transcripts were induced to 500 molecules per cell at day 9, whereas induction of vitellogenin II messenger RNA was not found until day 11. Thus, two estrogen regulated genes of common function and coordinately regulated in the adult may be on independent developmental programs.

Animals↗
PubMed1984

Apolipoprotein II messenger RNA. Transcriptional and splicing heterogeneity yields six 5'-untranslated leader sequences.

The structure of the mRNA for apolipoprotein II (apo-II), a major avian estrogen-responsive yolk protein, has been investigated. Primer extension using a cDNA probe-primer revealed six forms of mature apo-II mRNA. S1 and primer extension analysis with intron probes showed that only three of these forms arise due to multiple sites of transcription initiation on the apo-II gene. To investigate the basis for the additional forms of apo-II mRNA, we examined their nucleotide sequence. The sequence obtained between -10 and -42, relative to translation initiation, is identical to that reported by Wieringa et al. (Wieringa, B., AB, G., and Gruber, M. (1981) Nucleic Acids Res. 9, 469-499). At position -43, however, sequence heterogeneity appears. The minor form of the sequence starting at -43 and extending in a 5' direction corresponds exactly to the published mRNA sequence. The major form of the sequence has the insertion, 5'-CAG-3', at this position. The apparent basis for this heterogeneity is an unusual intron-exon border which violates the consensus sequence found in comparable positions in most eukaryotic genes by the existence of two adjacent 5'-CAG-3' triplets after the pyrimidine (Y)-rich track. The processing ratio between intron removal at the upstream and downstream AG dinucleotide is approximately 2.5:1. This result demonstrates that the splicing mechanism allows spatial flexibility in the positioning of the highly conserved YAG triplet within the consensus sequence at the 3' splice site.

Animals↗
PubMed1984

Dihydrolipoamide dehydrogenase from halophilic archaebacteria.

Dihydrolipoamide dehydrogenase has been discovered in the halophilic archaebacteria for the first time. The enzyme from both classical and alkaliphilic halobacteria has been investigated. (1) The enzyme specifically catalysed the stoichiometric oxidation of dihydrolipoamide by NAD+. Enzymic activity was optimal at 2 M-NaCl and was remarkably resistant to thermal denaturation. (2) The relative molecular masses (Mr) of the native enzyme from the various species of halobacteria were determined to be within the range 112000-120000. (3) The enzyme exhibited a hyperbolic dependence of catalytic activity on both dihydrolipoamide and NAD+ concentrations. From these steady-state kinetic measurements the dissociation constant (Ks) of dihydrolipoamide was determined to be 57 (+/- 5) microM. (4) The enzyme was only susceptible to inactivation by iodoacetic acid in the presence of its reducing ligands, dihydrolipoamide or NADH. The rate of inactivation followed a hyperbolic dependence on the concentration of dihydrolipoamide, from which the Ks of this substrate was calculated to be 55 (+/- 7) microM. Together with the steady-state kinetic data, the pattern of inactivations is consistent with the involvement in catalysis of a reversibly reducible disulphide bond, as has been found in dihydrolipoamide dehydrogenase from non-archaebacterial species. In eubacterial and eukaryotic organisms, dihydrolipoamide dehydrogenase functions in the 2-oxo acid dehydrogenase complexes. These multienzyme systems have not been detected in the archaebacteria, and, in the context of this apparent absence, the possible function and evolutionary significance of archaebacterial dihydrolipoamide dehydrogenase are discussed.

Archaea↗