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Biomedical subjects

C D Smith

Publications and source records attributed to C D Smith.

At least 181 records · Page 10Linked to original sources
PubMed1993

Gastric acid secretion and vitamin B12 absorption after vertical Roux-en-Y gastric bypass for morbid obesity.

OBJECTIVE: This study sought to determine the basal and peak-stimulated acid secretion from the proximal gastric pouch and its relationship to absorption of free and food-bound vitamin B12 after gastric bypass for morbid obesity. SUMMARY BACKGROUND DATA: Gastric bypass can be performed safely and provides acceptable weight loss, but concerns remain about possible long-term complications such as vitamin B12 malabsorption. The authors hypothesized that by constructing a small pouch of gastric cardia, acid secretion into the pouch would be low, leading to maldigestion of food-bound vitamin B12 with subsequent malabsorption. METHODS: Basal and pentagastrin-stimulated peak acid outputs from the proximal gastric pouch were measured in ten patients after vertical Roux-en-Y gastric bypass using a perfused orogastric tube technique. Absorption of free and food-bound 57Co-vitamin B12 was evaluated separately using 24-hour urinary excretion. RESULTS: Basal (mEq/hr, mean +/- standard error of the mean [SEM]) and peak-stimulated (mEq/30 min) acid secretions from the proximal gastric pouch were markedly decreased compared to those for age- and sex-matched hospital control subjects (0.01 +/- 0.01 vs. 4.97 +/- 0.66 and 0.08 +/- 0.04 vs. 12.11 +/- 1.34, respectively; p < 0.001 for each). While absorption of free vitamin B12 was not statistically different from that of control subjects (11 +/- 2 vs. 15 +/- 2%; p > 0.05), absorption of food-bound vitamin B12 was decreased (0.8 +/- 0.2 vs. 3.7 +/- 0.5%; p < 0.01). CONCLUSIONS: After vertical Roux-en-Y gastric bypass for morbid obesity, acid secretion is virtually absent and food-bound vitamin B12 is maldigested and subsequently malabsorbed. The results of this study suggest that postoperative vitamin B12 supplementation is important and can be achieved with either monthly parenteral vitamin B12 or daily oral crystalline preparations.

Adult↗
PubMed1993

Reoperative bariatric surgery. Lessons learned to improve patient selection and results.

OBJECTIVE: The purpose of this study was to determine the spectrum of presentation, safety, and efficacy of operative bariatric surgery. SUMMARY BACKGROUND DATA: The only lasting therapy for medically complicated clinically severe obesity is bariatric surgery. Several operative approaches have resulted in disappointing long-term weight loss or an unacceptable incidence of complications that require revisionary surgery. METHODS: Sixty-one consecutive patients who underwent reoperative bariatric surgery from 1985 to 1990 were observed prospectively. One, two, or three previous bariatric procedures had been performed in 77%, 18%, and 5% of patients, respectively. Reoperation was required for unsatisfactory weight loss after gastroplasty or gastric bypass (61%), metabolic complications of jejunoileal bypass (23%), or other complications (16%), including stomal obstruction, alkaline- or acid-reflux esophagitis, and anastomotic ulcer. Revisionary procedures included conversion to vertical banded gastroplasty (33% of operations) and vertical Roux-en-Y gastric bypass (52% of operations); partial pancreato-biliary bypass was used selectively in four patients with severe, medically complicated obesity. RESULTS: A single patient died postoperatively of a pulmonary embolus; serious morbidity occurred in 11%. Weight loss (mean +/- SEM) after reoperation for unsuccessful weight loss was greater with gastric bypass than with vertical banded gastroplasty (54 +/- 6% versus 24 +/- 6% of excess body weight). Metabolic complications of jejunoileal bypass were corrected, but 67% of the patients were dissatisfied with their postoperative lifestyle because of changes in eating habits or weight gain (64% of patients). Stomal complications and esophageal reflux symptoms were reversed in all patients. CONCLUSIONS: Reoperative bariatric surgery in selected patients is safe and effective for unsatisfactory weight loss or for complications of previous bariatric procedures. Conversion to gastric bypass provides more effective weight loss than vertical banded gastroplasty.

Adult↗
PubMed1993

Plasmodium coatneyi ring-infected erythrocyte surface antigens.

Plasmodium coatneyi produced ring-infected erythrocyte surface antigen (RESA) during infection of the rhesus monkey. This antigen was immunogenic and elicited an antibody response that was not persistent but was boosted by repeated infections in a manner similar to that seen in P. falciparum infections in humans. Preliminary data showed that the appearance and increasing titer of antibodies to P. coatneyi RESA-like antigen were associated with prolongation of intervals from inoculation to patency and with control of parasitemia. Studies using both immunofluorescence assay and Western blot analysis showed that P. coatneyi-immune rhesus serum cross-reacted with P. falciparum antigens, but P. falciparum immune human serum did not recognize P. coatneyi antigens in either assay. These results show that P. coatneyi expresses RESA-like antigen that elicits an antibody response similar to that observed for human antibody to P. falciparum RESA. However, antibodies to P. coatneyi did not cross-react with P. falciparum RESA in erythrocyte membrane immunofluorescence assay and dot immunoblot analysis, suggesting that different immunogenic epitopes are present on the two molecules. Our observations support the use of this primate model in RESA-based vaccine development.

Animals↗
PubMed1993

Causal prophylactic and radical curative activity of WR182393 (a guanylhydrazone) against Plasmodium cynomolgi in Macaca mulatta.

Primaquine is the only currently available drug effective against persistent tissue stages of relapsing malaria in humans. Causal prophylactic and radical curative properties of WR182393 (a guanylhydrazone) were investigated as part of an effort to evaluate alternatives to primaquine in the rhesus monkey (Macaca mulatta)/Plasmodium cynomolgi test model. The drug was suspended in dimethylsulfoxide for intramuscular (im) injection. A pilot study indicated causal prophylactic activity in a regimen of 40 mg base/kg/day im for three days beginning the day before intravenous challenge with 1 x 10(6) P. cynomolgi sporozoites. Regimens of 31, 10, 3.1, and 0 mg base/kg/day im for three days were then tested in groups of two monkeys given a similar challenge. The two animals given 31 mg base/kg/day remained parasite-free. Average time to parasitemia for the lower dosage groups was 38, 18, and 8 days respectively. Groups of two monkeys with sporozoite-induced P. cynomolgi infections were also treated for seven days with 31, 10, 3.1, and 0 mg base/kg/day im in combination with 10 mg base/kg/day of chloroquine orally. Both monkeys given 31 mg base/kg/day did not relapse. The average time to relapse following treatment was 48, 29, and 8 days, respectively, for the lower dosage groups. Compound WR182393 is the first non-8-aminoquinoline class of drug to exhibit both causal prophylactic and radical curative properties against a relapsing primate, vivax-like malaria.

Animals↗
PubMed1993

Sequestration pattern of parasitized erythrocytes in cerebrum, mid-brain, and cerebellum of Plasmodium coatneyi-infected rhesus monkeys (Macaca mulatta).

Six rhesus monkeys (Macaca mulatta) infected with Plasmodium coatneyi were studied for parasitized red blood cell (PRBC) sequestration in microvessels of the brain. The degree of PRBC sequestration is different in the cerebral, mid-brain, and cerebellar microvessels, with sequestration occurring preferentially in the cerebellum. This pattern resembles that of PRBC sequestration in cerebral and cerebellar microvessels in human falciparum malaria. The morphologic appearance of sequestered cells under light and electron microscopy as well as the PRBC sequestration pattern bolsters the contention that the rhesus monkey infected with P. coatneyi is an appropriate primate model for the experimental study of human cerebral malaria.

Animals↗
PubMed1993

A nonhuman primate model for human cerebral malaria: effects of artesunate (qinghaosu derivative) on rhesus monkeys experimentally infected with Plasmodium coatneyi.

We studied the effects of artesunate on rhesus monkeys infected with Plasmodium coatneyi. Sixteen rhesus monkeys were divided in four groups. Group I consisted of three monkeys that were splenectomized and were treated with three doses (loading dose: 3.3 mg/kg, maintenance doses: 1.7 mg/kg) of artesunate, group II consisted of three monkeys that were treated with three doses of artesunate (same as group I), group III consisted of two monkeys that were treated with one dose (3.3 mg/kg) of artesunate, and group IV consisted of five untreated monkeys. Parasitemias of these groups ranged from 13.3% to 19.5% before treatment. Twenty-four hours after administration, the parasitemia was reduced to 2.2% in group I and to < 0.1% in group II; parasitemia was lowered to 10.6% in group III only 3 hr after drug administration. The rate of sequestration in the cerebral microvessels, which was 29.4% in untreated animals, was < 0.1% in groups I and II (24 hr after treatment), and 2.0% in group III (3 hr after treatment). These data clearly indicate that artesunate not only reduced parasitemia, but also reduced the rate of parasitized red blood cell (PRBC) sequestration in cerebral microvessels. In an immunohistologic study, endothelial-leukocyte adhesion molecule-1 (ELAM-1) was not detected in group I after treatment with artesunate, although the presence of CD36, thrombospondin, intercellular adhesion molecule-1, IgG, and C3 in the cerebral microvessels was not altered. This is the first in vivo study to show that artesunate interferes with continued PRBC sequestration in the cerebral microvessels in cerebral malaria.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Fibrolase. A fibrinolytic protein from snake venom.

Fibrolase is an active fibrinolytic agent and possesses potential for use in thrombolytic therapy. Its mode of action had been characterized, both in vitro and in vivo. Possessing three disulfide bonds, native fibrolase is nonglycosylated and binds an intrinsic zinc atom. The zinc is essential for retention of activity and structural integrity. In solution, fibrolase is sensitive to changes in pH and temperature (Pretzer et al., 1991). At neutral to basic pH (pH 5-9), the solubility and stability of fibrolase is nearly constant. Little structural variation can be detected by CD spectroscopy. However, decrease in pH below 5 leads to a pronounced reduction in both the solubility and activity of fibrolase. At pH 3 and below, the solubility of fibrolase returns but the activity does not. This solubility profile is unusual in that the minimal solubility is well removed from the pI (which is 6.7). It is proposed that the behavior of fibrolase with variation in pH can be understood in terms of capacity to bind zinc. At pH 5 to 9, the protein binds zinc and the structure and activity are preserved. Near pH 5, the histidine residues which serve as ligands for the zinc become protonated and zinc binding is lost. Loss of zinc leads to local unfolding of a helical segment of fibrolase, exposing hydrophobic groups which allow the protein to rapidly aggregate. At lower pH values (1-3), the protein again adopts a more globular structure, similar to molten globule states, and the solubility increases. However, without the zinc, fibrolase remains inactive. Changes in pH also affect thermal stability. The Tm for fibrolase moves from 50 degrees C at pH 8 to 43 degrees C at pH 5. Increases in temperature also lead to removal of the zinc ion, again producing a partially denatured protein with a marked tendency to aggregate. In both cases (decrease in pH and increase in temperature), analysis of the CD spectra indicates that the protein has primarily lost alpha-helical secondary structure. A major change in structure can also be observed using NMR spectroscopy. At temperatures below 35 degrees C, the globular structure of fibrolase remains intact, although some increase in chain mobility can be noted with increased temperature. Upon melting, numerous signals collapse as the protein unfolds. Transition temperatures (Tm) as measured by CD and NMR are in good agreement. Similar structural changes can be induced by adding zinc chelators such as EDTA and DTT. This leads to complete loss of activity at EDTA concentrations above 1.0 mM.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1992

Peroxynitrite-mediated tyrosine nitration catalyzed by superoxide dismutase.

Peroxynitrite (ONOO-), the reaction product of superoxide (O2-) and nitric oxide (NO), may be a major cytotoxic agent produced during inflammation, sepsis, and ischemia/reperfusion. Bovine Cu,Zn superoxide dismutase reacted with peroxynitrite to form a stable yellow protein-bound adduct identified as nitrotyrosine. The uv-visible spectrum of the peroxynitrite-modified superoxide dismutase was highly pH dependent, exhibiting a peak at 438 nm at alkaline pH that shifts to 356 nm at acidic pH. An equivalent uv-visible spectrum was obtained by Cu,Zn superoxide dismutase treated with tetranitromethane. The Raman spectrum of authentic nitrotyrosine was contained in the spectrum of peroxynitrite-modified Cu,Zn superoxide dismutase. The reaction was specific for peroxynitrite because no significant amounts of nitrotyrosine were formed with nitric oxide (NO), nitrogen dioxide (NO2), nitrite (NO2-), or nitrate (NO3-). Removal of the copper from the Cu,Zn superoxide dismutase prevented formation of nitrotyrosine by peroxynitrite. The mechanism appears to involve peroxynitrite initially reacting with the active site copper to form an intermediate with the reactivity of nitronium ion (NO2+), which then nitrates tyrosine on a second molecule of superoxide dismutase. In the absence of exogenous phenolics, the rate of nitration of tyrosine followed second-order kinetics with respect to Cu,Zn superoxide dismutase concentration, proceeding at a rate of 1.0 +/- 0.1 M-1.s-1. Peroxynitrite-mediated nitration of tyrosine was also observed with the Mn and Fe superoxide dismutases as well as other copper-containing proteins.

Animals↗
PubMed1992

Expression of the cardiac Na(+)-Ca2+ exchanger in insect cells using a baculovirus vector.

We constructed a recombinant baculovirus containing cardiac Na(+)-Ca2+ exchanger cDNA under control of the polyhedrin promoter. When either Sf9 or Sf21 insect cells are infected with the recombinant baculovirus, both Na(+)-Ca2+ exchanger protein and Na(+)-Ca2+ exchange activity are expressed at high level. The exchanger protein can be detected either by immunoblot or by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of whole cell lysate. At maximal expression, the exchanger protein comprises about 3-5% of total cell protein. The Na(+)-Ca2+ exchanger can be purified by alkaline extraction of infected cells followed by elution from a Bio-Rad Prep Cell. The expressed exchanger, in contrast to the native sarcolemmal exchanger, is not glycosylated. Sf9 cells expressing the exchanger are intensely stained by anti-exchanger antibodies as observed by immunofluorescence. The expressed exchanger is predominantly in the cell plasma membrane since it is susceptible to extracellular trypsin. In 45Ca2+ flux experiments, the expressed Na(+)-Ca2+ exchange activity is about 4-fold higher than that in cultured neonatal rat heart cells. The expressed exchanger was also analyzed electrophysiologically using whole cell patch clamp techniques. The characteristics of inward exchange currents in infected Sf21 cells are very similar to those of ventricular myocytes, although of a larger magnitude.

Animals↗
PubMed1992

Baculovirus-mediated expression of the Na+/glucose cotransporter in Sf9 cells.

We have used baculovirus (AcNPV) to express the Na+/glucose cotransporter protein in cultured Sf9 cells. We constructed a baculovirus transfer vector containing the cDNA for the rabbit intestinal Na+/glucose cotransporter (SGLT1) under the control of the polyhedrin gene promoter. Recombinant baculovirus was obtained by cotransfection of SF9 cells with wild-type AcNPV DNA and the transfer vector. Recombinant virus was identified by Southern blotting and then purified. Recombinant infected Sf9 cells expressed a protein which was recognized by anti-peptide antibodies raised to sequences of the cloned Na+/glucose cotransporter. This protein migrated with a molecular mass of 55 kD by SDS-PAGE, similar to the in vitro translation product of SGLT1. An identical protein was metabolically labeled with [35S]methionine. Cells which synthesized the transport protein showed Na(+)-dependent alpha MeGlc transport. Micromolar phlorizin inhibited transport. Uninfected and wild-type virus infected Sf9 cells did not have Na(+)-dependent glucose transport. All transport protein migrated at 45% sucrose (w/w) by density gradient sedimentation, suggesting that the expressed transporter is membrane associated. We conclude that we have functionally expressed the rabbit intestinal Na+/glucose cotransporter in Sf9 cells. The transporter is not heavily glycosylated, and this is consistent with previous work showing that glycosylation is not necessary for function. We are poised to purify and characterize this protein from a structure-function perspective.

Amino Acid Sequence↗
PubMed1992

Inhibition of phosphatidylinositol 4-phosphate kinase by heparin. A possible mechanism for the antiproliferative effects of heparin.

Heparin and related glycosaminoglycans are important modulators of vascular smooth muscle cell growth, and may be involved in pathological processes such as atherosclerosis. Since polyphosphoinositide metabolism is a major mechanism for regulating cellular activities, including proliferation, the effects of glycosaminoglycans and polyanionic compounds on the activities of phosphoinositide kinases were characterized. Heparin and heparan sulphate caused dose-dependent inhibitions of rat brain cytosolic phosphatidylinositol 4-phosphate (PIP) kinase activity, with half-maximal inhibitory concentrations of approx. 0.5 and 5 microM respectively. PIP kinase was also inhibited by several dextran sulphates, but was not sensitive to inhibition by keratin sulphate, chondroitin sulphate or hyaluronic acid. Polynucleotides and acidic polypeptides were only weakly inhibitory. Heparin did not alter either the PIP- or the Mg(2+)-dependence of PIP kinase. Addition of heparin to brain membranes suppressed PIP kinase activity without affecting phosphatidylinositol (PI) kinase activity. Heparin interfered with the ability of a GTP analogue to stimulate PIP kinase activity in these membranes, suggesting that it uncouples the kinase from an activating guanine-nucleotide-binding protein. In cultured A-10 vascular smooth muscle cells, heparin caused dose- and time-dependent inhibition of [3H]thymidine incorporation into DNA. Similar treatments with heparin decreased cellular levels of phosphatidylinositol 4,5-bisphosphate (PIP2) without changing PI and PIP levels. Therefore heparin-mediated inhibition of PIP kinase appears to lead to decreases in PIP2 levels which may attenuate cellular proliferation.

Animals↗
PubMed1992

Crystal structure of peroxynitrite-modified bovine Cu,Zn superoxide dismutase.

The crystal structure of bovine Cu,Zn superoxide dismutase modified with peroxynitrite (ONOO-) was determined by X-ray diffraction, utilizing the existing three-dimensional model of the native structure deposited in the Brookhaven Protein Data Bank (J. A. Tainer et al., J. Mol. Biol. 160, 181-217, 1982). The native structure and the modified derivative were refined to R factors of 19.0 and 18.7% respectively using diffraction data from 6.0 to 2.5 A. The major result after reaction with peroxynitrite was the appearance of electron density 1.45 A from a single epsilon carbon of Tyr-108, the only tyrosine residue in the sequence. Tyr-108 is a solvent-exposed residue 18 A from the copper atom in the active site. The electron density was consistent with nitration of Tyr-108 at one of the epsilon carbons to form 3-nitrotyrosine. We propose that the nitration occurs in solution by transfer of a nitronium-like species from the active site on one superoxide dismutase dimer to the Tyr-108 of a second dimer.

Animals↗
PubMed1992

Perinatal ovarian cyst: a nonsurgical approach.

A case of an ovarian cyst diagnosed antenatally by ultrasound and showing spontaneous resolution within 5 months after birth is presented. On the basis of this case and others reported in the literature, we recommend expectant follow-up of such lesions with operation recommended only for cysts with solid or complex components or cysts causing symptoms from large size or torsion.

Female↗
PubMed1992

The role of myoneural and luminal continuity in the coordination of canine gastroduodenal patterns of motility.

Our aim was to determine the role of intrinsic myoneural and enteric luminal continuity in the coordination of gastric and duodenal motility patterns. Three groups of dogs were prepared: five dogs with an intact gastrointestinal tract served as a Control group; four dogs had transection and reanastomosis of the duodenum 0.5 cm distal to the pylorus (Pyloric Transection group); and seven dogs had identical proximal duodenal transection, but with oversewing of duodenum and pylorojejunostomy to a Roux-en-Y limb (Roux-en-Y group). In the Control and Pyloric Transection groups, the gastric and intestinal MMCs were similar in appearance, the cycle durations (x +/- SEM) were not different (134 +/- 19 vs 111 +/- 26 min, respectively; P > 0.05), and the times between the start of gastric and duodenal Phase III (gastroduodenal latency) were similar (6 +/- 1 vs 10 +/- 3 min; P > 0.05). In the Roux-en-Y group, MMCs also occurred in six of seven dogs but tended to have a longer cycle duration (176 +/- 19 min) and a more variable gastroduodenal latency (23 +/- 15 min). Plasma motilin concentration, measured only in the Roux-en-Y group, was greater during Phase III in the stomach and duodenum than during Phases I or II (P < 0.05). Feeding inhibited the gastric and duodenal MMCs in all groups, but the duodenal MMC returned earlier in the Roux-en-Y group. The Roux-en-Y jejunal limb exhibited a postprandial pattern in only seven of 14 studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Impact of spinal cord repair kinetics on the practice of altered fractionation schedules.

The kinetics of repair of sublethal lesions in the spinal cord was assessed in detail using a rodent model. Experiments were designed to obtain the fractionation sensitivity, alpha/beta, and to quantify the kinetics of repair after a clinically relevant fraction size. Pairs of 2-Gy fractions at intervals ranging from 0 to 24 h were given from Monday through Friday, to cumulative doses of 40-84 Gy. In addition, two groups of animals received 1.5 or 1.2 Gy twice a day at 8-h intervals, 5 days a week, to total doses of 66-90 Gy and 67.2-98.4 Gy, respectively. All irradiations were followed by a top-up dose of 16 Gy. Analysis of the experimental data revealed that a bi-exponential repair model fit the experimental data significantly better than did the mono-exponential model (p = 0.002). The repair half times obtained were 0.7 (0.2-1.3) h and 3.8 (2.6-4.9) h, respectively. The proportion of injury repaired by the longer half time was estimated to be 0.62 (0.37-0.86). The data showed that delivering 2 fractions per day at 6- or 8-h intervals instead of one per day led to a 16.5% (11.8-21.1%) and 13.5% (9.1-17.8%) reduction in the tolerance, respectively. Finally, the results indicated that when incomplete repair between fractions was accounted for, the linear-quadratic (LQ) model was valid in describing fractionation response down to 1.2 Gy per fraction.

Animals↗