Search PubMed⌕ Search

Biomedical subjects

S Grant

Publications and source records attributed to S Grant.

At least 235 records · Page 13Linked to original sources
PubMed1991

Effect of plasma triglyceride concentrations on the accuracy of immunoturbidimetric assays of apolipoprotein B.

We have studied the influence of triglyceride-rich particles on the analytical bias of apolipoprotein B measurements by various immunoturbidimetric methods. Three commercially available methods grossly overestimate apolipoprotein B in samples with even moderately above-normal triglyceride concentrations. This effect is due to the increased relative reactivity of very-low-density lipoproteins in these reagent systems, and can be eliminated by including Tween 20 (2 g/L) in the reagent buffer. We have developed, and describe, an automated immunoturbidimetric method that allows the accurate determination of apolipoprotein B in the plasma of patients with hypertriglyceridemia.

Apolipoproteins B↗
PubMed1991

Effect of the protein kinase C activating agent bryostatin 1 on the clonogenic response of leukemic blast progenitors to recombinant granulocyte-macrophage colony-stimulating factor.

Bryostatin 1 is a macrocyclic lactone activator of protein kinase C which has displayed promising antileukemic potential in pre-clinical studies. We have assessed the effect of bryostatin 1 on the in vitro clonogenic response of leukemic myeloblasts obtained from 12 patients with acute non-lymphocytic leukemia to recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF), and have compared these responses to those of normal human hematopoietic progenitors. Although leukemic blast progenitors responded in a heterogenous manner to bryostatin 1 as a single agent, co-administration of 12.5 or 100 nM bryostatin 1 in conjunction with 1.25 ng/ml rGM-CSF resulted in a significant reduction in colony formation (compared to rGM-CSF alone) in 8/12 specimens, and sub-additive stimulatory effects in all samples. In addition, the exposure of cells to 12.5 nM bryostatin 1, either alone or in conjunction with 1.25 ng/ml rGM-CSF, substantially reduced or eliminated leukemic cell self-renewal capacity in all samples assayed. In contrast to the effects observed in leukemic cells, exposure of adherent and T-cell depleted normal bone marrow mononuclear cells to equivalent concentrations of bryostatin 1 and rGM-CSF consistently produced supra-additive effects on the growth of normal committed myeloid progenitors (day 14 CFU-GM). When normal marrow cells were further enriched for progenitors (MY-10+), concentrations of bryostatin 1 that were unable to support growth when administered alone significantly potentiated the number of GM colonies formed in response to rGM-CSF. These studies suggest that bryostatin 1 may modulate the in vitro response of certain normal and leukemic progenitor cells to rGM-CSF, and that the nature of this response differs between the two cell types. They also indicate that bryostatin 1 may be particularly effective in limiting the self-renewal capacity of leukemic myeloblasts, an in vitro characteristic with potentially important in vivo significance.

Antigens↗
PubMed1990

Glutamate-like immunoreactivity in neurons of the laterodorsal tegmental and pedunculopontine nuclei in the rat.

Studies of the pedunculopontine (PPT) and laterodorsal tegmental (LDT) nuclei in the mesopontine tegmentum have emphasized the organization and projections of the cholinergic neurons. We report here that exhibiting glutamate immunoreactivity are present in both the LDT and PPT. These glutamatergic neurons are interspersed among the cholinergic neurons within both nuclei with no apparent segregation. These data raise the possibility that excitatory amino acids contribute to the functions of the LDT and PPT.

Animals↗
PubMed1990

Selective overexpression of the QUTE gene encoding catabolic 3-dehydroquinase in multicopy transformants of Aspergillus nidulans.

The three enzymes necessary to catabolize quinate to protocatechuate are inducible by quinic acid, and transcription of their corresponding genes is controlled by the action of a positively acting activator gene and a negatively acting repressor gene. Transformed strains of Aspergillus nidulans containing multiple copies of the activator gene (QUTA) but single copies of the other QUT genes retain normal regulation of the gene cluster and do not show any overexpression of the three quinic acid catabolic enzymes. Transformed strains containing equal multiple copies of the activator gene (QUTA) and QUTE (encoding catabolic 3-dehydroquinase), but single copies of the other QUT genes, retain normal regulation of the QUT gene cluster, but selectively overexpress the QUTE gene upon quinic acid induction. Data are presented that strongly suggested that the gene QUTG, which is physically located within the QUT gene cluster and for which no function has been identified, is not required for expression of the gene cluster and does not encode a chlorogenic acid esterase.

Aspergillus nidulans↗
PubMed1990

Excision of the En/Spm transposable element of Zea mays requires two element-encoded proteins.

An excision assay system for En/Spm was developed in transgenic tobacco. The characteristics of excision and integration are similar to the natural system of Zea mays. In this transgenic model system two En/Spm encoded trans-acting functions, TNPA and TNPD, are required for excision. A biochemical model for transposition is proposed that might also be applicable to other transposable elements.

Cloning, Molecular↗
PubMed1990

Biochemical modulation of cytosine arabinoside.

1-beta-D arabinofuranosylcytosine (ara-C) is an analog of the naturally occurring nucleoside 2'-deoxycytidine which is a potent antileukemic agent in man. Because the metabolism (and, ultimately, the effectiveness) of this agent is regulated by multiple processes involved in pyrimidine biosynthesis, attempts to improve its efficacy through biochemical modulation have been the focus of intense interest. These approaches have included combination of ara-C with inhibitors of de novo pyrimidine biosynthesis, deaminase inhibitors, nucleoside transport blockers, nucleosides, and more recently, hematopoietic growth factors. Although potentiation of ara-C metabolism and cytotoxicity has been documented in multiple experimental in vitro and in vivo experimental systems, clinical studies in humans have thus far failed to document definitive improvements in ara-C selectivity and efficacy through biochemical modulation. It is likely that such improvements will require the identification of more optimal schedules, sequences and dose relationships, and possibly combined modality approaches.

Animals↗
PubMed1990

The effect in vitro of 2'-deoxycytidine on the metabolism and cytotoxicity of 2',3'-dideoxycytidine.

We examined in vitro the effect of high, but clinically achievable and non-toxic, concentrations of 2'-deoxycytidine (dCyd) (greater than or equal to 100 mumols/l on the metabolism and cytotoxicity of 2',3'-dideoxycytidine (DDC) in normal human bone marrow mononuclear cells (BMMCs) and a cultured T-lymphocyte (HUT-102) cell line. Colony formation in semi-solid medium by bone marrow progenitor cells (CFU-GM and CFU-GEMM) was significantly protected by dCyd against the cytotoxic effects of high doses of DDC. In contrast, in HIV-infected HUT-102 cells, anti-HIV effect of DDC (10 mumols/l) was preserved in the presence of 100 mumols/l dCyd but partially reversed by higher levels of dCyd. dCyd reduced the generation of DDC triphosphate (DDC-TP) relative to dCyd triphosphate (dCTP) pools to a significantly greater extent in BMMCs versus HUT-102 cells. This might explain dCyd-mediated abrogation of DDC cytotoxicity against marrow progenitor cells with relative preservation of its anti-HIV-1 activity in HUT-102 cells.

Cell Line↗
PubMed1990

Novel exercise protocol suitable for use on a treadmill or a bicycle ergometer.

Many exercise protocols are in use in clinical cardiology, but no single test is applicable to the wide range of patients' exercise capacity. A new protocol was devised that starts at a low workload and increases by 15% of the previous workload every minute. This is the first protocol to be based on exponential rather than linear increments in workload. The new protocol (standardised exponential exercise protocol, STEEP) is suitable for use on either a treadmill or a bicycle ergometer. This protocol was compared with standard protocols in 30 healthy male volunteers, each of whom performed four exercise tests: the STEEP treadmill and bicycle protocols, a modified Bruce treadmill protocol, and a 20 W/min bicycle protocol. During the two STEEP tests the subjects' oxygen consumption rose gradually and exponentially and there was close agreement between the bicycle and the treadmill protocols. A higher proportion of subjects completed the treadmill than the bicycle protocol. Submaximal heart rates were slightly higher during the bicycle test. The STEEP protocol took less time than the modified Bruce treadmill protocol, which tended to produce plateaux in oxygen consumption during the early stages. The 20 W/min bicycle protocol does not take account of subjects' body weight and consequently produced large intersubject variability in oxygen consumption. The STEEP protocol can be used on either a treadmill or a bicycle ergometer and it should be suitable for a wide range of patients.

Adult↗
PubMed1990

Differences between multisite postmortem ethanol concentrations as related to agonal events.

In a study of postmortem ethanol concentrations, blood was withdrawn from the right atrium, ascending aorta, and inferior vena cava. These samples, vitreous humor, and gastric fluid were analyzed in 307 autopsies, where a minimum blood ethanol concentration of 0.05% weight/volume (w/v) was present. Premortem, agonal, and postmortem events were reviewed in an attempt to account for differences in blood ethanol concentrations between sites. The agonal aspiration of vomitus having at least 0.80% w/v ethanol appears to be associated with an increase in aortic ethanol concentrations. We conclude that valid interpretation of postmortem ethanol concentrations must take into consideration the possible entry of ethanol into the pulmonary venous circulation via the respiratory system.

Adult↗
PubMed1990

The effect of a prolonged in vitro exposure to 1-beta-D arabinofuranosylcytosine and deoxycytidine on the survival of normal (CFU-GM) and leukemic (L-CFU) human myeloid progenitor cells in suspension culture.

We examined the effect of a 96-h exposure to 1-beta-D arabinofuranosylcytosine (Ara-C) and deoxycytidine (dCyd) in medium lacking an exogenous source of colony-stimulating activity (phytohemagglutinin-stimulated leukocyte-conditioned medium, PHA-LCM) on the survival of normal human committed myeloid progenitor cells (day-7 and day-14 granulocyte-macrophage colony-forming units [CFU-GM] as well as leukemic progenitors (leukemic colony-forming units, L-CFU) derived from myeloblasts obtained from 13 patients with acute nonlymphocytic leukemia (ANLL). Coadministration of Ara-C (20-50 microM) in conjunction with dCyd (50-100 microM) permitted the survival of an average of 9%-57% of day-7 CFU-GM and 32%-65% day-14 CFU-GM, depending upon the relative concentrations of dCyd and Ara-C. In contrast, exposure of leukemic myeloblasts to identical regimens resulted in considerably greater reductions in L-CFU survival, which in general exceeded 90% and in some cases was 100%. In addition, exposure of leukemic myeloblasts to Ara-C and dCyd for 96 h in culture medium lacking PHA-LCM eliminated the secondary plating efficiency (PE2) of leukemic colonies in 11 of 13 samples assayed and reduced values dramatically in the remaining 2. Substantial preservation of CFU-GM formation was also noted when normal bone marrow samples depleted of T cells and marrows obtained from two patients with ANLL in remission were assayed. These studies suggest that in contrast to certain normal committed myeloid progenitor cells, leukemic progenitors, particularly those with self-renewal capacity, are highly vulnerable to a prolonged exposure to Ara-C and dCyd in the absence of an exogenous source of colony-stimulating activity. They also raise the possibility that a combined regimen utilizing chemotherapeutic agents in conjunction with modifications of long-term culture techniques may represent a novel approach to the ex vivo purging of leukemic cells from bone marrow in conjunction with autologous bone marrow transplantation.

Cell Survival↗
PubMed1990

Various levels of maternal caffeine ingestion during gestation affects biochemical parameters of fetal rat brain differently.

Pregnant dams were divided into four groups on day 10 of gestation. Dams of group 1 were fed an 20% protein diet as controls. Dams of groups 2, 3 and 4 were fed a 20% protein diet supplemented with 0.5 mg, 1 mg and 2 mg caffeine/100 g body weight of dams, respectively. Pups were delivered surgically on day 22, and their brains were rapidly removed and analyzed for DNA, protein, cholesterol, zinc and alkaline phosphatase activity. The dams' brains were analyzed for the same parameters as those of the pups. Plasma and brain caffeine levels were also determined in caffeine-supplemented groups. The pups' brains in group 2 were heavier than those in group 4. The DNA concentration of group 2 was higher than that of the other groups. The protein concentration of group 4 was higher than that of the other groups. The cholesterol concentration of group 3 and 4 was less than that of the controls. The zinc concentration of group 4 was less than that of group 2. Alkaline phosphatase activity was decreased in groups 3 and 4 compared with either controls or group 2. Dams showed no significant difference among the groups in the same biochemical parameters except for cholesterol concentration that was higher in groups 2, 3 and 4 than in the controls. Plasma and brain caffeine levels of the fetuses and plasma caffeine of the dams in group 4 were higher than those of either group 2 or 3. It is concluded that various amounts of maternal caffeine intake exert different effects on fetal brain growth. In contrast, the effect of caffeine on the dams' brain is relatively minor.

Animals↗
PubMed1989

2'-Deoxycytidine protects normal human bone marrow progenitor cells in vitro against the cytotoxicity of 3'-azido-3'-deoxythymidine with preservation of antiretroviral activity.

Bone marrow cytotoxicity of 3'-azido-3'-deoxythymidine (AZT), an anti-human immunodeficiency virus (anti-HIV) drug, has been attributed to deoxyribonucleotide pool perturbations that might result in impaired DNA synthesis in normal bone marrow elements. We examined, in vitro, the effect of high, but clinically achievable and nontoxic, concentrations of 2'-deoxycytidine (dCyd) (greater than or equal to 100 mumol/L) on high-dose AZT mediated growth inhibition and intracellular biochemical perturbations in normal bone marrow progenitor cells. Colony formation by bone marrow progenitor cells in semisolid medium was significantly protected by dCyd against the inhibitory effects of co-administered, high concentrations of AZT (10 mumol/L). Also, dCyd significantly corrected AZT mediated depletion of intracellular thymidine triphosphate (dTTP) and dCyd triphosphate (dCTP) levels in normal bone marrow mononuclear cells (BMMC). Moreover, dCyd reduced the intracellular accumulation of AZT triphosphate (AZT-TP) and its DNA incorporation in BMMC. In contrast, co-administration of dCyd (100 mumol/L to 1 mmol/L) did not reverse AZT (10 mumol/L) mediated suppression of HIV infectivity in HUT-102 cells in culture, although a partial reduction in intracellular AZT-TP pools and its DNA incorporation as well as a correction of AZT mediated depletion of dTTP and dCTP pools was observed in these cells. These studies suggest that dCyd at high concentrations might ameliorate the bone marrow cytotoxicity of high-dose AZT without impairing its anti-HIV effect.

Bone Marrow↗
PubMed1989

Changing patterns of binocular visual connections in the intertectal system during development of the frog, Xenopus laevis. I. Normal maturational changes in response to changing binocular geometry.

During metamorphic and post-metamorphic life in the frog. Xenopus laevis, growth-related changes in skull shape produce radical alterations in the spatial relationship between the two eyes. These changes in binocular visual geometry were measured using optical techniques. Between the onset of metamorphic climax at stage 60 and adulthood (2 or more years post-metamorphosis) each eye migrates nasally by 55 degrees and dorsally by 50 degrees with respect to the major body axes of the animal. As a result the nasotemporal extent of the binocular visual field increases from 30 degrees to 162 degrees between these ages. Electrophysiological methods were used to determine changes in the neural representation of the binocular visual field at the paired midbrain optic tecta and in the tectal projection of pairs of corresponding retinal loci at various developmental points between these ages. The proportion of each tectal surface devoted to the representation of the binocular visual field increases from 11% at stage 60 to 77% at adulthood. Retinal correspondence, and hence the tectal projection of corresponding retinal loci, undergoes radical alteration during this period. In normal adults an intertectal system of connections selectively links the tectal projection of corresponding retinal loci and thus provides a neuronal mechanism for integrating binocular visual information in the optic tecta. Electrophysiological methods were used to determine how the intertectal system accommodates the developmental challenge posed by the enlarging binocular visual field and changing retinal correspondence. Between stage 60 and adulthood the ipsilateral visuotectal projection which is the product of the intertectal system, increases in size as the binocular visual field and its tectal representation enlarges. Moreover, throughout this period, it provides a mechanism for integrating binocular visual information in the optic tecta by maintaining its spatial registration with the contralateral visuotectal projection from the other eye. Analysis of the pattern of functional intertectal connections reveals that during the course of normal maturation this system undergoes continuous processes of expansion and of orderly and major remodelling.

Action Potentials↗
PubMed1989

Changing patterns of binocular visual connections in the intertectal system during development of the frog, Xenopus laevis. II. Abnormalities following early visual deprivation.

During normal metamorphic and post-metamorphic growth of the frog, Xenopus laevis, there is a major and orderly remodelling of the pattern of neuronal connections in the intertectal system. These changes preserve the spatial registration of binocular visual inputs to each optic tectum in the face of continuous changes in relative eye alignment (Grant and Keating 1989). We suggested that visual experience might be utilised by the intertectal system to effect the maturational remodelling of its connections, with particular involvement in maintaining binocular visual registration. To investigate this suggestion we studied the development of the intertectal system in animals that had been reared in total darkness from before the onset of function in the system. Visual deprivation did not affect the developmental ocular migration that normally occurs in Xenopus, nor did it affect the maturation of the contralateral visuotectal projection. Abnormalities were, however, observed in the ipsilateral visuotectal projection of all dark-reared animals studied, reflecting perturbation of the underlying intertectal system. The abnormalities included disorder and deficits in the projection, which became more marked with age. Quantitative analyses of the spatial registration of binocular visual inputs to the optic tectum revealed that, in all dark-reared animals studied, registration was both significantly poorer and systematically shifted compared to normal controls. Analysis of maturational changes in the pattern of intertectal connections in visually-deprived animals led to the conclusion that intrinsic developmental processes generate an initially well-organised intertectal system and programme much of its continuous expansion with age. Visual experience, however, is necessary for the large scale and orderly remodelling of the system which, during normal maturation, preserves binocular visual registration despite changes in interocular alignment.

Action Potentials↗
PubMed1989

The effects of maternal caffeine intake during pregnancy on mineral contents of fetal rat bone.

Various levels of maternal caffeine ingestion during pregnancy were investigated to determine whether caffeine will affect the mineral contents of the growing bones of fetal rats. On day 8 of gestation, rat dams were fed with a 20% protein diet supplemented with 0.5 mg, 1 mg, or 2 mg caffeine/100 g of dams body weight as an experimental group and the same without caffeine as a control until day 22 of gestation. Fetuses were removed by cesarean section on day 22 and mandibular bones were removed to study the mineral contents of calcium, phosphorus, magnesium, and zinc. Although the mandible weighed more in the 0.5-mg caffeine group as compared to the controls, an additional increase of caffeine resulted in a decrease in weight. All calcium, magnesium, and zinc contents per bone decreased in the 1- and 2-mg caffeine groups as compared to either controls or 0.5-mg caffeine group, whereas phosphorus stayed relatively constant regardless of the different levels of caffeine intake. When data are expressed as per gram of bone tissue, most of the mineral contents among the groups disappeared suggesting that normal growth and development of the fetal bone are impaired as a results of maternal caffeine intake. Caffeine intake during gestation in the present study indicates that different levels of caffeine intake may exert not only different effects on mineral contents in bone development, but also affect the growth of the fetal bone.

Animals↗
PubMed1989

Effect of diagnostic and therapeutic cordocentesis on maternal serum alpha-fetoprotein concentration.

We investigated the affect of cordocentesis (n = 36) and intravascular transfusion (n = 14) performed with a fixed needle guide on maternal serum alpha-fetoprotein levels. In 50% of the procedures, the placenta was anterior and punctured. For all patients, maternal serum alpha-fetoprotein levels rose 70.8% +/- 28%. The magnitude of the rise was unrelated to the number of attempts necessary, gestational age, or the initial maternal serum alpha-fetoprotein levels concentration. The location of the placenta was the sole identified variable related to the rise. A total of 44% of the patients had a significant increase in maternal serum alpha-fetoprotein level when the placenta was anterior. In contrast, only 4% of the patients had a significant rise in maternal serum alpha-fetoprotein level when the placenta was other than anterior. There was no difference in the frequency of a significant rise in maternal serum alpha-fetoprotein level concentration between the patients who underwent cordocentesis and those who underwent intravascular transfusion. On the basis of these findings, we recommend that when maternal isoimmunization is a potential concern and the placenta is anterior, the umbilical cord should be approached either through a window or laterally from the placenta.

Amniocentesis↗