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Biomedical subjects

C H Smith

Publications and source records attributed to C H Smith.

At least 19 recordsLinked to original sources
PubMed1992

Human placental syncytiotrophoblast expresses two pharmacologically distinguishable types of Na(+)-H+ exchangers, NHE-1 in the maternal-facing (brush border) membrane and NHE-2 in the fetal-facing (basal) membrane.

We investigated whether highly purified preparations of basal (fetal-facing) membrane isolated from normal term human placentas possess Na(+)-H+ exchanger activity. Uptake of Na+ into basal membrane vesicles was stimulated many-fold by an outwardly directed H+ gradient. This H(+)-gradient-dependent uptake was inhibitable by amiloride and its analogues. Na+ uptake in these vesicles did not occur via a Na+ channel, as it was not influenced by changes in membrane potential and, in addition, was inhibited by benzamil only at high micromolar concentrations. The results indicate that the human placental basal membrane possesses Na(+)-H+ exchanger activity. We then studied whether this exchanger is similar to or distinct from the Na(+)-H+ exchanger described in brush border (maternal-facing) membrane preparations. For this purpose, we compared the pharmacological characteristics of the basal membrane Na(+)-H+ exchanger with those of the brush border membrane Na(+)-H+ exchanger. The basal membrane exchanger was about 20-fold less sensitive to inhibition by amiloride and about 70-fold less sensitive to inhibition by dimethylamiloride than was the brush border membrane exchanger. The exchanger activity in both membrane preparations was inhibitable by clonidine and cimetidine, but the inhibition patterns with these compounds were markedly different between basal and brush border membrane preparations. These data demonstrate that the basal membrane Na(+)-H+ exchanger is distinct from the brush border membrane Na(+)-H+ exchanger. The pharmacological profiles of these exchangers indicate that the human placental brush border membrane possesses the housekeeping or non-epithelial type Na(+)-H+ exchanger (NHE-1), whereas the basal membrane possesses the epithelial or apical type Na(+)-H+ exchanger (NHE-2).

Basement Membrane↗
PubMed1992

Cutaneous responses to vasoactive intestinal polypeptide in chronic idiopathic urticaria.

Cutaneous wheal and flare responses to increasing concentrations of calcitonin gene-related peptide, substance P, neurokinin A, vasoactive intestinal polypeptide (VIP), compound 48/80, and phosphate-buffered saline were measured in 10 patients with chronic idiopathic urticaria and 10 healthy controls. A significant increase in VIP-induced wheal, but not flare or cutaneous blood flow, was seen in urticarial patients compared with controls (p less than 0.001). No significant differences in responses to other tested compounds were found between these groups. These data point to an increased sensitivity of microvasculature to VIP in patients with chronic idiopathic urticaria.

Adult↗
PubMed1992

Cutaneous histamine metabolism in chronic urticaria.

Impaired metabolism of histamine in the skin of patients with chronic idiopathic urticaria (CIU) might explain the observed enhanced and prolonged skin responses to intradermal histamine. Histamine metabolism was measured in homogenates from unaffected forearm skin in nine patients with CIU and in skin of age- and sex-matched control subjects with a radiochromatographic assay, and the results are expressed as nanograms of histamine metabolized per milligram of protein per hour. Endogenous histamine content was determined by RIA. There was a highly significant increase in endogenous histamine content in the skin of patients with urticaria (407.8 +/- 188.3 ng/mg of protein) compared with that in skin of control subjects (240.0 +/- 73.0 ng/mg of protein) (mean +/- 1 SD; p less than 0.02), which suggests either an increase in mast cell number or histamine concentration per cell. No significant difference was observed in the metabolism of histamine between patient and control group; therefore, an alternative mechanism may underlie differences in skin reactivity to histamine.

Chronic Disease↗
PubMed1992

Transport and binding in calcium uptake by microvillous membrane of human placenta.

Calcium entry across the microvillous membrane of the human placental syncytiotrophoblast is the first step in the transfer of this important nutrient to the fetus. Calcium uptake by isolated microvillous membranes was time dependent. Equilibrium uptake was very much greater than could be explained by equilibration of the vesicle space with medium, indicating that calcium is bound to internal sites. Addition of the ionophore A23187 greatly increased the rates of influx and efflux, indicating that transport across the plasma membrane is rate limiting in entry. Concentration dependence data for calcium transport at 4 s fit well to a Michaelis-Menten equation having two saturable sites and diffusion. Calcium entry by both transporters was unaffected by calcium channel blockers but was strongly inhibited by the group II metals. The distinct inhibition constant values for strontium inhibition provided additional evidence for two transporters. Calcium binding fit well to a single-site model saturable in the micromolar range. In vivo, the saturable transport processes may mediate calcium entry into the syncytiotrophoblast and binding may regulate concentration within the placental microvilli.

Barium↗
PubMed1992

Macroamylases: differences in activity against various-size substrates.

Hyperamylasemia caused by macroamylases can lead to the overdiagnosis of acute pancreatitis. We examined whether interference from macroamylase is less in assays that use high-molecular-weight rather than oligosaccharide substrates. We hypothesized that high-molecular-weight substrates would be sterically excluded from macroamylasemic complexes and thus would be hydrolyzed less efficiently. Eighteen macroamylasemic samples were assayed by using red-dyed amylopectin or blue-dyed starch as polysaccharide substrates or by using maltoheptaose or maltotetraose as oligosaccharide substrates. The oligosaccharide substrates gave comparable results (y = 0.81x + 83); we observed consistently lower activities for amylopectin than for maltotetraose (y = 0.32x + 38). We observed no bias among methods when nonmacroamylasemic specimens were analyzed. The mechanism of this difference was examined by adding anti-human pancreatic amylase antibodies to hyperamylasemic serum samples from patients without macroamylasemia and purified human pancreatic or salivary isoamylases. In each case, polyclonal and monoclonal antibodies lowered amylase activity more in assays with complex polysaccharides than in those with oligosaccharides. The use of high-molecular-weight substrates diminishes interference, and detection of suspected macroamylasemia may be possible through comparison of activities determined from automated methods that use different substrates.

Amylases↗
PubMed1992

Macroamylases: differences in activity against various-sized substrates.

Hyperamylasemia caused by macroamylases can lead to the overdiagnosis of acute pancreatitis. We examined whether interference from macroamylase is less in assays that use high-molecular-mass (high-M(r)) substrates rather than oligosaccharide substrates. We hypothesized that high-M(r) substrates would be sterically excluded from macroamylasemic complexes and thus would be hydrolyzed less efficiently. Eighteen macroamylasemic samples were assayed by using red-dyed amylopectin or blue-dyed starch as polysaccharide substrates or by using maltoheptaose or maltotetraose as oligosaccharide substrates. The oligosaccharide substrates gave comparable results (y = 0.81x + 83), but we observed consistently lower activities for amylopectin than for maltotetraose (y = 0.32x + 38). We observed no bias among methods when nonmacroamylasemic specimens were analyzed. The mechanism of this difference was examined by adding antihuman pancreatic amylase antibodies to hyperamylasemic serum samples from patients without macroamylasemia and to purified human pancreatic or salivary isoamylases. In each case, polyclonal and monoclonal antibodies lowered amylase activity more in assays with complex polysaccharides than in those with oligosaccharides. The use of high-M(r) substrates diminishes interference, and detection of suspected macroamylasemia may be possible through comparing activities determined from automated methods that use different substrates.

Amylases↗
PubMed1992

Cell culture of macular epiretinal membranes.

To attempt to differentiate the cells of origin in epiretinal membranes, cells were cultured from an idiopathic epiretinal membrane and an epiretinal membrane that formed after successful repair of a retinal detachment. The cells exhibited a variety of forms. When the cells from the idiopathic epiretinal membrane were incubated with melanin from donor eyes a population of small cells accumulated the pigment, but the large, flat cells did not. The epiretinal membrane was not composed of a single cell type. Although a population of cells exists within epiretinal membranes, no one cell type could be identified as the cell type of origin.

Aged↗
PubMed1991

Asymptomatic orbital cavernous hemangiomas.

Computed tomographic (CT) scanning and magnetic resonance imaging (MRI) are commonly performed to evaluate neurologic symptoms. Rarely are asymptomatic orbital tumors discovered, creating uncertainty about their management. Eleven patients are presented who were referred for asymptomatic orbital tumors discovered on either CT scanning or MRI performed for unrelated symptoms of headache, vertigo, peripheral numbness, seizures, stroke, or hallucinations. The asymptomatic orbital tumors were diagnosed clinically and radiologically as cavernous hemangiomas. All the patients were followed clinically and neuroradiologically for an average of 37 months (range, 8 to 120 months). None of the tumors enlarged during this time. The authors conclude that patients who have asymptomatic cavernous hemangiomas, discovered by coincidence during neuroimaging, that bear no relation to the indication for obtaining the CT scan or MRI, can be safely followed by observation as an alternative to surgical excision.

Adult↗
PubMed1991

Two cationic amino acid transport systems in human placental basal plasma membranes.

Transport of cationic amino acids in basal (fetal facing) plasma membranes was investigated by characterization of L-[3H]lysine and L-[3H]arginine uptake in membrane vesicles isolated from term human placentas. At least two Na(+)-independent systems were present. Lysine concentration dependence data were fit by a two-system model with Km values of 1.0 +/- 0.8 and 223 +/- 57 microM and Vmax values of 0.06 +/- 0.03 and 24.0 +/- 5.8 pmol.mg protein-1.min-1. In the presence of either 10 mM L-leucine or Na+ plus 10 mM L-homoserine, the data were fit by single system models with kinetic parameters similar to the higher and lower Km systems seen in the absence of inhibitors. Uptake of 10 or 20 microM L-lysine in the absence of Na+ showed the higher Km system was inhibited completely by L-arginine, L-homoarginine, and L-histidine. In the presence of Na+, the higher Km system was inhibited completely by L-alanine, L-homoserine, L-leucine, L-phenylalanine, and L-norleucine. The lower Km system was inhibited completely by L-arginine, L-homoarginine, L-histidine, L-leucine, and L-methionine. Time course studies of uptake demonstrated that uptake by either system alone filled the total vesicular space. The basal membrane of human placental syncytiotrophoblast possesses two transport systems for lysine and arginine, resembling the ubiquitous y+ system and the bo,+ system previously described in mouse blastocysts. The higher Vmax of the y+ system suggests that in utero it may mediate transfer of cationic amino acids from the syncytiotrophoblast to the fetus. The role of the high-affinity low-capacity bo,+ system remains to be determined.

Amino Acids↗
PubMed1991

Pentose phosphate pathway in cellular trophoblasts from full-term human placentas.

Glucose metabolism was investigated in cellular trophoblasts isolated from full-term human placentas. The specific yields of 14CO2 from D-[1-14C]glucose and D-[6-14C]glucose were used to determine glucose metabolism via the pentose cycle for cells freshly isolated or cells grown in culture for 1 and 3 days. Cells were mononucleated on day 1 but fused to form multinucleated syncytiotrophoblasts by day 3. The principal product of glucose metabolism under all conditions was lactate, accounting for approximately three-fourths of recovered 14C in products. Pentose cycle activity contributed 0.57 +/- 0.01, 0.39 +/- 0.06, and 0.21 +/- 0.05% of the glucose metabolized by cells freshly isolated, cultured for 1 day, and cultured for 3 days, respectively. In the presence of the electron acceptor methylene blue, pentose cycle activity increased to 16.5 +/- 2.1, 13.8 +/- 1.5, and 18.2 +/- 1.7% for cells freshly isolated, cultured for 1 day, and cultured for 3 days, respectively. Trace amounts of 14C were recovered in other products including amino acids and glycogen. These data suggest that pentose cycle activity in cellular trophoblasts from full-term placenta, like those in full-term villous tissue, is a minor component of glucose metabolism. However, these cultured cells maintain a capacity to oxidize glucose via the pentose cycle at relatively high rates.

Carbon Radioisotopes↗
PubMed1991

Adrienne Rich, Ruth Whitman, and their Jewish elders.

Adrienne Rich's portraits of her paternal, Jewish elders confirm the view that elders who suppress their ties to Judaism suffer psychologically as they age; however, Rich's depiction of her Jewish mother-in-law shows that elders who maintain their ties can also suffer depression in later stages. In contrast, Ruth Whitman shows that her Jewish grandmothers maintained ties and were content in old age; at the same time, her paternal Jewish grandfather aged peacefully even though he rebelled against Judaism. The portraits drawn by these poets come from a breadth of thinking that tolerates ambiguities, goes beyond generalities to individual differences, and permits sympathy in the midst of criticism.

Adaptation, Psychological↗
PubMed1990

The calcium-transporting ATPase and the calcium- or magnesium-dependent nucleotide phosphatase activities of human placental trophoblast basal plasma membrane are separate enzyme activities.

The properties of calcium-stimulated ATP hydrolysis often differ from those of ATP-dependent calcium transport. We have characterized two components of calcium-stimulated ATP hydrolysis in human placental basal plasma membrane. In the absence of magnesium, component 1 apparently has saturable sites for free calcium in both the nanomolar and low micromolar range. It was stimulated by either calcium or magnesium, was unselective for nucleotide substrate, and its activity was very much greater than that of ATP-dependent calcium transport. Component 1 was inhibited by GTP, permitting measurement of component 2 with activity and magnesium stimulation comparable to ATP-dependent calcium transport. Component 2 was inhibited partially by an antibody against purified erythrocyte calcium transporter and completely by sulfhydryl reagents, whereas component 1 was unaffected. A phosphorylated intermediate of the calcium transporter co-migrated with the erythrocyte transporter on acidic sodium dodecyl sulfate-polyacrylamide electrophoresis gels. Immunostaining after transfer to nitrocellulose revealed a doublet. The band of lower molecular weight co-migrated with that of the human erythrocyte membrane transporter. The addition of GTP permits separate measurement of ATP hydrolysis by the calcium transporter of the placental basal plasma membrane and may be useful in defining its properties in other cell membranes under a variety of conditions.

Adenosine Triphosphatases↗
PubMed1990

Anionic amino acid transport systems in isolated basal plasma membrane of human placenta.

The placenta absorbs anionic amino acids from the maternal and fetal circulations but does not significantly transfer these amino acids from mother to fetus. Uptake of L-aspartate and L-glutamate by basal (fetal-facing) plasma membrane vesicles from placental syncytiotrophoblast was stimulated by an inward sodium and an outward potassium gradient. Measurable saturable uptake was entirely sodium dependent and electrogenic. Studies of concentration dependence resolved a high-affinity (microM) system that has characteristics of the X-AG system found in other tissues including the placental microvillous plasma membrane. Uptake of 0.2 microM L-glutamate was inhibited by 2 mM L-glutamate, L-aspartate, D-aspartate, L-cysteate, and L-cysteinesulfinic acid and was uninhibited by 2 mM D-glutamate, L-glutamine, L-alanine, L-serine, L-asparagine, and taurine or by 1 mM methylaminoisobutyric acid. The X-AG system in the two membranes of the placental syncytiotrophoblast may mediate the concentrative uptake of anionic amino acids from the maternal and fetal circulations into the placenta.

Amino Acids↗
PubMed1990

In pursuit of the moment.

When one paper is a sequel to a previous one, it is altogether too simple to bore the reader with redundancies. It is also quite too easy to lose track of time and jump from one paper to the next and this almost certainly will happen in the present one. Portions of the earlier writing are initially presented and one would hope that these present a valid reason to continue pursuit of "The Moment." After some discussion, it is felt that various previously unmentioned facets of "The Moment" are discussed and perhaps clarified. But it is not defined. It may defy definition and we could hope that this might intensify our pursuit, since physicians are a stubborn group.

Physician-Patient Relations↗