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Biomedical subjects

G N Smith

Publications and source records attributed to G N Smith.

At least 91 records · Page 5Linked to original sources
PubMed1991

Effects of alcohol (ethanol) on the fetus.

Alcohol (ethanol) use during pregnancy can produce a wide spectrum of effects in the developing embryo/fetus that are dependent on the maternal drinking pattern. The effects of chronic ethanol exposure on the developing conceptus are reviewed with primary focus on ethanol teratogenesis, manifesting in the human as the fetal alcohol syndrome or fetal alcohol effects. The effects of acute ethanol exposure on the near-term fetus are described, including suppressed fetal breathing movements, electrocorticographic (ECoG) activity and electrooculographic (EOG) activity. The ethanol-induced suppression of fetal breathing movements is a very sensitive index of acute exposure of the near-term fetus to ethanol, and appears to involve a direct mechanism of action rather than an indirect mechanism involving suppression of electrocortical activity. The disposition of ethanol and its pharmacologically active proximate metabolite, acetaldehyde, and the activity of alcohol dehydrogenase and aldehyde dehydrogenase in the near-term maternal-fetal unit are described, and a pharmacokinetic model is proposed. The effects of short-term ethanol exposure on the near-term fetus include the development of tolerance to the ethanol-induced suppression of fetal breathing movements, low-voltage ECoG activity and EOG activity. The development of tolerance occurs more rapidly to the latter two fetal biophysical activities. The mechanism of tolerance development appears to be pharmacodynamic (functional) in nature, as there is no increase in the rate of ethanol elimination from the maternal-fetal unit. The role of prostaglandins (PGs) in the mechanism of the ethanol-induced suppression of fetal breathing movements is described. In the near-term fetus, there is a direct relationship between fetal blood ethanol concentration and fetal plasma PGE2 concentration, and an inverse relationship between the incidence of fetal breathing movements and each of fetal plasma and fetal cerebrospinal fluid (CSF) PGE2 concentrations. Indomethacin, a PG synthetase inhibitor, selectively blocks and reverses the ethanol-induced suppression of fetal breathing movements. These data support the postulates that the ethanol-induced suppression of fetal breathing movements is mediated by increased PGE2 concentration in the near-term fetus and that the ability of indomethacin to antagonize the ethanol-induced suppression of fetal breathing movements is due to its biochemical action to decrease fetal PGE2 concentration.(ABSTRACT TRUNCATED AT 400 WORDS)

Alcohol Drinking↗
PubMed1991

Effect of ethanol on 15-hydroxyprostaglandin dehydrogenase activity in the brain stem of the near-term fetal sheep.

The effect of in vitro incubation with ethanol (10-80 mM) on 15-hydroxyprostaglandin dehydrogenase (15-OH-PGDH) activity was determined in the brain stem (pons and medulla) of the fetal sheep at a mean gestational age of 126 days (term: about 147 days). Enzyme activity was determined by measuring the rate of oxidation of PGE2 to 15-keto-PGE2 using a radiometric assay. There was no statistically significant ethanol-induced inhibition of 15-OH-PGDH activity. The data apparently do not support the hypothesis that acute in vitro exposure to ethanol directly inhibits 15-OH-PGDH activity in the near-term fetal brain stem.

Animals↗
PubMed1990

Type XI collagen-degrading activity in human osteoarthritic cartilage.

Homogenates of 6 samples of human osteoarthritic cartilage were shown to degrade exogenous type XI collagen. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the cleavage products generated by each homogenate were similar, and they were identical to those obtained by cleavage of the substrate with purified gelatinase. Enzyme activity, which was inhibited by EDTA, was greater in extracts of fibrillated osteoarthritic cartilage than in extracts of grossly normal cartilage from the same joint or in extracts of cartilage from joints with osteonecrosis. Activation with APMA enhanced digestion, but breakdown was apparent in extracts of fibrillated osteoarthritic cartilage even without APMA. Enzymatic degradation of type XI collagen could play a significant role in the turnover of articular cartilage in health and disease states.

Adolescent↗
PubMed1990

Indomethacin reversal of ethanol-induced suppression of ovine fetal breathing movements and relationship to prostaglandin E2.

The effects of indomethacin on the ethanol-induced suppression of fetal breathing movements and fetal arterial plasma and cerebrospinal fluid (CSF) PGE2 concentrations and maternal arterial plasma PGE2 concentration were determined in the near-term fetal lamb. Eight conscious instrumented pregnant ewes (between 130 and 133 days of gestation; term, 147 days) received 1-h maternal intravenous infusion of 1 g ethanol/kg total body weight, and the fetus received 6-h intravenous infusion of indomethacin (1 mg/h per kg fetal body weight) commencing 30 min later. Serial fetal and maternal arterial blood samples (n = 8) and fetal CSF samples (n = 5) were collected at selected times throughout the 12-h study for the determination of PGE2 concentration. Fetal breathing movements were monitored continuously throughout the experimental period. Maternal ethanol infusion resulted in initial suppression (P less than 0.05) of fetal breathing movements for 2 h below pretreatment value, followed by a rapid increase in the incidence of fetal breathing movements after the onset of fetal indomethacin treatment. Fetal and maternal plasma PGE2 concentrations and fetal CSF PGE2 concentration were increased (P less than 0.05) above the pre-infusion value during the administration of ethanol and 1 h thereafter. Fetal indomethacin treatment suppressed (P less than 0.05) to undetectable levels fetal plasma and CSF PGE2 concentrations, which then became similar (P greater than 0.05) to pretreatment by 12 h. There was a positive correlation between fetal plasma and CSF PGE2 concentrations. There was an inverse correlation between the incidence of fetal breathing movements and fetal CSF PGE2 concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Effect of ethanol on ovine fetal and maternal plasma prostaglandin E2 concentrations and fetal breathing movements.

The effect of maternal administration of ethanol on fetal and maternal plasma prostaglandin E2 (PGE2) concentrations and fetal breathing movement was determined in the near-term pregnant ewe. Six conscious instrumented pregnant ewes (between 129 and 134 days of gestation; term, 147 days) were studied on two successive days (day 1 and day 2). On each of the two days of the experiment, there was a 1-h period of maternal infusion of ethanol (1 g ethanol/kg total body weight) or an equivalent volume of normal saline. Animals were assigned to two groups with one group (n = 3) receiving ethanol on day 1 and saline on day 2, and the other group (n = 3) receiving saline on day 1 and ethanol on day 2. Fetal and maternal blood samples were collected at selected times for blood ethanol determination (n = 2), and plasma was obtained for the determination of PGE2 concentration (n = 6). Fetal breathing movements were monitored continuously during the experimental periods. Maternal saline infusion had no effect (P greater than 0.05) on fetal breathing movement and fetal and maternal plasma PGE2 concentrations (187 +/- 25 (SEM) pg/ml and 196 +/- 32 pg/ml, respectively). Maternal ethanol infusion suppressed (P less than 0.05) fetal breathing movement below preinfusion levels for 8 h and increased (P less than 0.05) both fetal and maternal plasma PGE2 concentrations to 314 +/- 55 pg/ml and 306 +/- 25 pg/ml, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium↗
PubMed1989

Type XI collagen is associated with the chondrocyte surface in suspension culture.

Chondrocytes from bovine articular cartilage were stripped of matrix, then allowed to reconstitute their pericellular matrix in suspension culture. After incubation, the cells were centrifuged through a Percoll (TM) cushion and separated into a cell fraction, a medium fraction, and an interface fraction. The collagen in each fraction was analyzed by SDS-polyacrylamide gel electrophoresis and immunolocation with antisera against type XI and type II. Under these conditions, type XI collagen was recovered in the cell fraction, but was not detectable by immunolocation in the medium fraction or the interface fraction. In contrast, type II collagen was found in all three of these fractions. Insoluble type XI fibers subjected to the same fractionation scheme in the absence of cells were recovered in the medium and interface fractions, but not in the cell fraction. Incubation of intact cells with collagenase digested the cell-associated collagen, indicating that it was outside of the cells. The type XI collagen was removed from the cells by extraction with 4 M guanidinium chloride. These results indicate that type XI collagen is preferentially retained at the chondrocyte surface, and are consistent with our proposal that it is involved in organization of the pericellular matrix.

Animals↗
PubMed1989

Effect of acute, multiple-dose ethanol on maternal and fetal blood gases and acid-base balance in the near-term pregnant ewe.

The effect of ethanol on maternal and fetal blood gases and acid-base balance was determined in six conscious instrumented near-term pregnant ewes for maternal intravenous infusion of 3 g ethanol/kg total body weight administered as six doses of 0.5 g ethanol/kg total body weight over 8 h. Maternal and fetal blood ethanol concentrations, determined in two animals, were maximal at 8 h (3.74 and 3.82 mg/mL, respectively) and were virtually identical during the 24-h study. Maternal and fetal blood gases and acid-base balance were not significantly altered during and after ethanol administration compared with preinfusion values. The data demonstrate that, during near-term ovine pregnancy, the equivalent of a binge-type drinking episode does not produce fetal hypoxia or acidosis. Furthermore, these data do not support the postulated involvement of ethanol-induced fetal hypoxia in the mechanism of ethanol teratogenesis.

Acid-Base Equilibrium↗
PubMed1989

Stimulation of glycosaminoglycan synthesis in cultured human dermal fibroblasts by interleukin 1. Induction of hyaluronic acid synthesis by natural and recombinant interleukin 1s and synthetic interleukin 1 beta peptide 163-171.

Hyaluronic acid (HA) is believed to play a critical role in wound healing and in morphogenesis. Factors controlling the production of HA by fibroblasts in normal and pathological states are not completely understood. In this report we have observed that natural human interleukin (IL-1)1 beta and human recombinant (hrIL)-1 alpha and beta are potent stimulators of HA production by fibroblasts in vitro. Hyaluronic acid is the major species of glycosaminoglycan (GAG) stimulated by IL-1 in fibroblasts. PGE2 does not appear to be involved directly in this IL-1 effect on fibroblasts, but stimulation of HA production by IL-1 is dependent on protein synthesis. The synthetic human IL-1 beta peptide 163-171 (Val-Gln-Gly-Glu-Glu-Ser-Asn-Asp-Lys), which has been previously shown to stimulate thymocyte proliferation but not fibroblast PGE2 production, is also able to stimulate fibroblast HA production. The synthesis and secretion of IL-1 by mononuclear phagocytes at sites of inflammation and immune reactions in vivo could potentially serve as a signal for fibroblasts to synthesize HA, which in turn could serve to facilitate and modulate reparative and immune processes by virtue of its ability to alter cell-cell, cell matrix, and cell-membrane receptor interactions.

Cells, Cultured↗
PubMed1989

Development of tolerance to ethanol-induced suppression of breathing movements and brain activity in the near-term fetal sheep during short-term maternal administration of ethanol.

The effect of short-term maternal ethanol administration on the ethanol-induced suppression of fetal breathing movements, electrocortical (ECoG) activity, and electroocular (EOG) activity was determined in the near-term fetal sheep. Twelve conscious instrumented pregnant ewes (between 125 and 139 days of gestation; term, 147 days) received 1-h intravenous infusion of 1 g ethanol/kg total body weight daily for six days (n = 6) or an equivalent volume of normal saline daily for six days (n = 6). On the seventh day, the ethanol- and saline-pretreated animals were administered 1 g ethanol/kg total body weight. A further six ewes received 1-h intravenous infusion of 1 g ethanol/kg total body weight (n = 3) or an equivalent volume of normal saline (n = 3) daily for thirteen days with both groups receiving 1 g ethanol/kg total body weight on day fourteen. Fetal ECoG and EOG activities, and fetal breathing movements were monitored continuously over the post- operative and experimental periods. Saline infusion had no significant effect on the parameters studied. Fetal breathing movements were suppressed for 8 h after the first ethanol dose, and were not significantly suppressed after fourteen days of once-daily, maternal ethanol administration. Low-voltage ECoG and EOG activities were suppressed for 3 h after the first ethanol dose, and were not significantly suppressed after seven days of repeated ethanol administration. Maternal and fetal blood gases and acid-base balance were not significantly affected by maternal ethanol administration. These data demonstrate that short-term maternal administration of ethanol results in the development of tolerance to ethanol in the mature fetus.

Animals↗
PubMed1989

Indomethacin antagonizes the ethanol-induced suppression of breathing activity but not the suppression of brain activity in the near-term fetal sheep.

The effect of indomethacin on the ethanol-induced suppression of fetal breathing movements, low-voltage electrocortical (ECoG) activity, and electro-ocular (EOG) activity was studied in the near-term fetal sheep. Ten conscious instrumented pregnant ewes (between 129 and 131 days of gestation; term, 147 days) received 1-h maternal intravenous infusion of 1 g ethanol/kg total body weight and simultaneous fetal treatment with either indomethacin (2 mg/kg fetal body weight/h) (n = 5) or an equivalent volume of phosphate buffer (n = 5) intravenously for 9 h. Fetal ECoG activity, EOG activity, and fetal breathing movements were monitored continuously over the experimental periods. In animals treated with ethanol and buffer (n = 5), fetal breathing movements were suppressed for 8 h and low-voltage ECoG and EOG activity was suppressed for 2 h below preinfusion levels. In animals treated with ethanol and indomethacin (n = 5), fetal breathing movements were elevated for 13 h but low-voltage ECoG and EOG activity remained suppressed for 3 h below preinfusion levels. The data suggests that indomethacin can antagonize the ethanol-induced suppression of fetal breathing movements, but does not alter the ethanol-induced suppression of ECoG or EOG activity.

Animals↗
PubMed1989

Activity of alcohol dehydrogenase and aldehyde dehydrogenase in maternal liver, fetal liver and placenta of the near-term pregnant ewe.

The activity of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) was determined in the near-term pregnant ewe. There was little ADH activity in fetal liver (4.4%) and placenta (0.2%) compared with maternal liver. Low KM (microM acetaldehyde) ALDH activity was similar in the three tissues. High KM (mM acetaldehyde) ALDH activity was less in fetal liver (57%) and placenta (16%) compared with maternal liver. These data and the pharmacokinetics of ethanol and its proximate metabolite, acetaldehyde, in the near-term pregnant ewe indicate that ethanol elimination from the maternal-fetal unit is regulated primarily by maternal hepatic ADH-catalyzed biotransformation of ethanol, and low KM ALDH activity in the fetal liver and placenta protects the fetus from exposure to ethanol-derived acetaldehyde, which is produced primarily in the maternal compartment.

Acetaldehyde↗
PubMed1988

Ventricular and sulcal size at the onset of psychosis.

To determine whether abnormalities in brain morphology are present at the onset of illness, patients with schizophrenia, schizophreniform and bipolar disorders, and major depression who were experiencing their first episodes of psychosis were compared with normal and medical control subjects. The schizophrenic patients had larger third ventricles but not larger lateral ventricles or cortical sulci than the normal subjects. The other psychotic patients did not differ from the normal group on these measures. A different pattern of results emerged when the medical patients were used for comparison, indicating that the choice of control group can influence the findings of computerized tomography studies.

Adolescent↗
PubMed1988

Choice of comparison group and findings of computerised tomography in schizophrenia.

The literature indicates that whether or not schizophrenic patients are reported to have significant lateral ventricular enlargement depends on control, and not schizophrenic-group values. This discrepancy does not result from differences in age, the ratio of males to females, the number of control subjects used in each study, or whether control groups are comprised of normal subjects or medical patients. However, medical-patient controls tend to have smaller ventricles than do normal individuals. Thus, we assessed lateral- and third-ventricle size and the degree of cortical atrophy in 30 normal volunteers, 30 medical patients, and 30 chronic schizophrenic patients. The use of a medical control group seemed to result in underestimates of ventricle and sulcal size in the normal population and, therefore, overestimates of these values in schizophrenic groups.

Adolescent↗
PubMed1988

Newt epidermal cell migration over collagen and fibronectin involves different mechanisms.

Effects of the synthetic peptides, Arg-Gly-Asp-Ser (RGDS), the amino acid sequence representing the fibroblast attachment site in fibronectin, and Arg-Gly-Glu-Ser (RGES), on collagen- and fibronectin-mediated migration in newt epidermal cells were compared. When RGDS at 50 micrograms ml-1 was included in the incubation medium of skin explants, migration in fibronectin-coated dishes was almost totally blocked. In type I collagen-coated dishes, this concentration of RGDS also inhibited migration, but to a lesser degree than on fibronectin. With 250 micrograms ml-1 of RGES in the medium, the reverse was true. Here, migration on collagen was practically non-existent, while migration on fibronectin was affected only moderately. Collagen-mediated migration was sensitive to RGDS even when the peptide was added after migration on the coated substratum was well underway. At a coating concentration of 10 micrograms ml-1 CB3, a cyanogen bromide fragment of the collagen alpha 1(I) chain, which contains no RGD sequences, was as good a migration substratum as intact collagen applied at the same coating concentration. At lower concentrations intact collagen was somewhat better than equivalent concentrations of CB3. The presence of RGDS in the medium throughout an experiment inhibited migration in CB3-coated dishes in a manner similar to its effect in dishes coated with collagen. On both substrata there appeared to be a peptide-sensitive and a peptide-insensitive component to migration. The inhibitory effect of RGES on CB3-mediated migration was also similar to its effect in collagen-coated dishes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗