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Biomedical subjects

D Chapman

Publications and source records attributed to D Chapman.

At least 145 records · Page 8Linked to original sources
PubMed1989

New haemocompatible polymers assessed by thrombelastography.

Mimicry of the nonthrombogenic surface of the erythrocyte has been advocated as the starting point for the development of nonthrombogenic biomaterials. Phosphorylcholine forms 88% of the outer surface of the erythrocyte, and so materials containing it should be nonthrombogenic. We have evaluated the thrombogenicity of such materials and compared them with Dacron and PTFE. Three materials containing phosphorylcholine were used: a naturally occurring phospholipid (dipalmitoylphosphatidylcholine, DPPC), a polymerized phospholipid (diacetylenic phosphatidylcholine, DAPC) and a polyester polyurethane (Polyester G). The thrombogenic potential of these materials was assessed by material thrombelastography (MTEG). This technique uses human whole blood at 37 degrees C, without an air interface, and records the elasticity of the blood clot produced. Since each material is evaluated with a control surface, extraneous differences due to factors other than the test material are eliminated. Analysis, and examples of the MTEG traces are shown and discussed. The phosphorylcholine containing materials were found to have a reduced amount of clotting factor activation, but only DPPC was better than Dacron and PTFE. MTEG demonstrated the known thrombogenicity of Dacron towards platelets. A striking reduction in platelet activation was shown for the three phosphorylcholine containing materials. These three materials show only 25% of the platelet activation of PTFE. These materials warrant further investigation as potentially very useful biomaterials.

Biocompatible Materials↗
PubMed1989

Biomembranes as models for polymer surfaces. V. Thrombelastographic studies of polymeric lipids and polyesters.

Our approach to the design of haemocompatible biomaterials is based upon the concept that coating a polymer or metal surface with phosphatidylcholine polar groups (corresponding to the major phospholipid of the human erythrocyte outer cell membrane) will improve their haemocompatibility. We have examined the effect on blood coagulation of a number of substrates: those normally used in prosthetic devices such as polyethylene terephthalate (Dacron), expanded polytetrafluoroethylene, silicone and new polymers which contain the phosphatidylcholine head group (phosphorylcholine). The effect on coagulation of blood exposed to these substrates was determined by the technique of material thrombelastography, a relatively new method for the in vitro screening of biomaterial thrombogenicity. The results obtained with Dacron, polytetrafluoroethylene and silicone are compared with those obtained with a phospholipid-dipalmitoyl-phosphatidylcholine, a polymerized phospholipid-diacetylenicphosphatidylcholine, and a range of recently synthesized polyesters, each of which contains the phosphorylcholine polar head group.

Biocompatible Materials↗
PubMed1989

Serum CA 125 levels and surgical findings in patients undergoing secondary operations for epithelial ovarian cancer.

Serum CA 125 levels and surgical findings were prospectively compared in 96 secondary laparotomies performed on patients with epithelial ovarian cancer. All patients had documentation of an elevated CA 125 level (greater than 35 U/ml) at a time when ovarian cancer was present, and thus the tumors were known to be "marker positive." Operation was performed in 45 patients who were clinically free of disease and in 51 patients in whom there was clinical evidence of disease. At the time of operation, 29 patients had normal CA 125 levels; persistent disease was documented in 18 (62%) of these. Of the patients with normal CA 125 levels at the time of operation, those with persistent disease had a significantly higher mean CA 125 level (16.9) than those with no disease detected (8.8, p = 0.001). At exploration, cancer was found in 84 patients. There was a correlation between the maximum diameter of the largest residual tumor mass and the accuracy of the CA 125 level as follows: microscopic to 1 cm disease, 55% accuracy; greater than 1 to 5 cm disease, 80% accuracy; greater than 5 cm disease, 92% accuracy (p = 0.013). There was no correlation of CA 125 accuracy with the patient's age, number of months from initial diagnosis, tumor stage, grade, or cell type, or the highest-ever level of CA 125. Of the 84 patients with tumor found at exploration, 66 had elevated CA 125 levels, yielding a sensitivity of 78.5%. There were 12 patients with no tumor found at exploration; 11 of these had normal CA 125 levels. The one patient who had an elevated CA 125 level subsequently had a recurrence; the corrected specificity is thus 100%. An elevated CA 125 level is an accurate predictor of persistent disease. Most of these patients will have gross tumor present. The accuracy of the CA 125 level in detecting disease is related to the amount of tumor present. In our population, the predictive value of an elevated CA 125 level was 100%; the predictive value of a normal CA 125 level was 38%.

Adult↗
PubMed1989

The bioavailability and pharmacokinetics of morphine after intravenous, oral and buccal administration in healthy volunteers.

1. The absolute bioavailability of morphine from oral aqueous solution, a controlled release oral tablet (MST-Continus) and a controlled release buccal tablet has been investigated in six healthy volunteers. 2. Analysis of plasma samples for morphine and its active metabolite morphine-6-glucuronide (M6G) was by means of a differential radioimmunoassay technique. Absolute bioavailability for morphine was estimated to be 23.9% after oral solution, 22.4% after MST-Continus and 18.7% after the buccal tablet. Maximum plasma morphine concentrations were seen at 45 min (oral solution), 2.5 h (MST) and 6 h (buccal). 3. There was no difference in the amount of M6G appearing in plasma after intravenous, oral or buccal administration but the mean ratio of AUCs for M6G: morphine in plasma after intravenous morphine was 2 : 1 compared with 11 : 1 after oral and buccal morphine.

Administration, Buccal↗
PubMed1989

Flow cytometry as a predictive indicator in patients with operable gastric cancer.

Adenocarcinoma of the proximal portion of the stomach (gastroesophageal [GE] junction and cardia) is increasing in incidence. The inferior survival of patients with GE-cardia lesions as compared with patients with tumors located in the body and antrum has been attributed to anatomic features. To determine if a biological difference could explain the varying prognosis, flow cytometric studies were performed prospectively in 50 patients with operable gastric cancer and analyzed for association with site, histology, gender, age, stage, and disease-free survival. DNA aneuploidy significantly correlated with tumor location: 96% of GE-cardia carcinomas were aneuploid as compared with 48% of body-antrum tumors (P = .0008). Nodal involvement was more common in aneuploid tumors (P = .0548), and women were more likely to have diploid tumors than were men (P = .0233). The median disease-free survival for patients with diploid tumors was 18.5 months as compared with 5.4 months for patients with aneuploid carcinomas (P = .076). Furthermore, within the body-antrum of the stomach, patients with diploid tumors had a significantly better disease-free survival than did those with aneuploid tumors from the same site (18.4 v 4.7 months, P = .0185). These results indicate there is a difference in the DNA content of gastric tumors located in different sites within the stomach and that DNA content correlates with prognosis.

Adenocarcinoma↗
PubMed1989

Intraperitoneal cisplatin and etoposide in the treatment of refractory/recurrent ovarian carcinoma.

To determine the efficacy of a 6-month course of combination intraperitoneal (IP) chemotherapy with cisplatin and etoposide in patients with refractory or recurrent advanced ovarian carcinoma, 67 patients were entered into this prospective, nonrandomized, single-institution trial. Cisplatin at 100 mg/m2 and etoposide at 200 mg/m2 were administered IP on day 1 every month for 6 months. Exploratory laparotomy was performed before protocol entry and was planned after the completion of 6 months of IP therapy to surgically document response. All patients had received prior intravenous (IV) chemotherapy with a cisplatin-based regimen. At protocol entry, 18 (27%) patients had surgically defined residual tumor (maximal tumor diameter) greater than 2.0 cm, 17 (25%) patients greater than 0.5 cm - less than or equal to 2.0 cm, and 32 (48%) patients less than or equal to 0.5 cm. Sixteen patients (24%) who had experienced a treatment-free interval of more than 1 year prior to study entry were considered as having recurrent disease and the remaining 51 (76%) patients were considered as having refractory disease. Toxicity was tolerable: four patients (6%) had nadir fever, three (4%) had culture-documented bacterial peritonitis, five (7%) had IP catheter-related complications, and 27 (40%) had an increase in serum creatinine greater than 1.5 mg/dL. Among the 57 patients who are fully evaluable for response, the overall surgically defined response rate, complete (CR), and partial response (PR), was 40% (23/57), and the CR rate was 21% (12/57). Among the patients with recurrent disease, eight of 13 (62%) responded, with responses seen among all categories of residual disease. Among the patients with refractory disease, 15 of 44 (34%) had surgically documented responses. However, responses were more frequent in patients with residual disease less than 0.5 cm; 11 of 20 (55%) versus four of 24 (17%) with residual greater than 0.5 cm, P = .019 (chi 2, one degree of freedom, Yates correction). The duration of the CRs ranges from 4 to 18+ months. Longer follow-up is needed to determine if there is any impact on survival.

Adult↗
PubMed1988

Proteolytic dissection as a probe of conformational changes in the human erythrocyte glucose transport protein.

Tryptic digestion has been used to investigate the conformational changes associated with substrate translocation by the human erythrocyte glucose transporter. The effects of substrates and inhibitors of transport on the rates of tryptic cleavage at the cytoplasmic surface of the membrane have confirmed previous observations that this protein can adopt at least two conformations. In the presence of phloretin or 4,6-O-ethylidene-D-glucose, the rate of cleavage is slowed. Because these inhibitors bind preferentially at the extracellular surface of the transporter, their effects must result from a conformational change rather than from steric hindrance. A conformational change must also be responsible for the effect of the physiological substrate D-glucose, which is to increase the rate of cleavage. The regions of the protein involved in the conformational changes include both of the large cytoplasmic regions that are cleaved by trypsin: these are the central hydrophilic region of the sequence (residues 213-269) and the hydrophilic C-terminal region (residues 457-492).

Erythrocytes↗
PubMed1988

Differential scanning calorimetric and Fourier transform infrared spectroscopic investigations of cerebroside polymorphism.

Calorimetric and Fourier transform infrared (FTIR) spectroscopic studies have been made of the polymorphism exhibited by bovine brain cerebroside-water systems, and the effect of cholesterol and dipalmitoylphosphatidylcholine (DPPC) upon this polymorphism was investigated. The conversion of the cerebroside from the thermodynamically stable to the metastable form is found to be accompanied by spectral changes, indicating a decrease in cerebroside headgroup hydration and a rearrangement of the hydrogen-bond network. The incorporation of low concentrations of cholesterol and DPPC into cerebroside bilayers broadens the thermal transitions associated with the cerebroside as a result of the disruption of cerebroside-cerebroside interactions. This disruption is evident in the spectra of cerebroside/cholesterol mixtures.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1988

The secondary structure of apolipoproteins in human HDL3 particles after chemical modification of their tyrosine, lysine, cysteine or arginine residues. A Fourier transform infrared spectroscopy study.

Fourier transform infrared spectra of apolipoprotein E-depleted human HDL3 have been obtained in H2O and 2H2O buffers. The absorption bands in the protein amide I and amide II regions (1700-1500 cm-1) were assigned to alpha-helical, disordered and beta-strand/beta-turn structures of apolipoproteins A-I and A-II (apoA-I and apoA-II), the apolipoprotein constituents of HDL3. Modification of HDL3 by tetranitromethane (TNM) treatment, acetylation, reduction plus alkylation and 1,2-cyclohexanedione treatment derivatised tyrosine, lysine, cysteine and arginine residues, respectively, and caused alteration of the secondary structure of the HDL3 apolipoproteins to different extents. Each of the chemical modifications caused changes in the frequency of bands associated with beta-strands/beta-turns, but only TNM treatment of HDL3, as judged by the second- and fourth-derivative spectra, resulted in a shift of the band assigned to the alpha-helical structure of the proteins. In agreement with other workers, only TNM treatment of HDL3 particles was found to inhibit their binding by high-affinity cell membrane receptors. It is proposed, therefore, that receptor recognition of HDL3 particles is dependent on conservation of the alpha-helix structures within apoA-I and apoA-II, and that beta-strand/beta-turn structures are not involved. This conclusion is consistent with the predominance of amphipathic alpha-helical structures in both apolipoproteins and with the relaxed specificity of the receptors which are thought to recognise both apoA-I and apoA-II.

Acylation↗
PubMed1988

Material thrombelastography: an assessment of phosphorylcholine compounds as models for biomaterials.

The use of phosphorylcholine (PC) containing compounds as possible biomaterials has been evaluated by material thrombelastography (MTEG). The detailed analysis of the MTEG technique is discussed. A remarkable reduction of thrombogenicity by compounds containing the PC group is demonstrated. The results observed with a polymerised PC-lipid indicate potential use of such substances as biomaterials with minimal thrombogenicity.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1988

Fourier transform infrared spectra of the polypeptide alamethicin and a possible structural similarity with bacteriorhodopsin.

FTIR spectra of alamethicin have been obtained in KBr disk, methanol and in aqueous lipid dispersion (above and below the lipid phase transition). The solution structure of this polypeptide in methanol has been shown by recent studies (Esposito et al. (1987) Biochemistry 26, 1043-1050) using NMR spectroscopy to be predominantly alpha-helical in content. It may therefore be regarded as a model structure for the interpretation of the spectra of certain biomembrane proteins. A comparison of the spectra with that obtained with bacteriorhodopsin shows spectral similarities, e.g. the presence of a high-frequency amide I maximum at 1661-1663 cm-1 and shoulders near 1640 cm-1 and 1620 cm-1.

Alamethicin↗
PubMed1988

Lipid-protein interaction. The incorporation of myelin proteolipid apoprotein into phosphatidylcholine bilayers.

Bovine myelin proteolipid apoprotein (PLA), obtained in high yield and purity by a novel ultrafiltration procedure, has been used to study the perturbations produced by this protein on phosphatidylcholine bilayers, using infrared spectroscopy, nuclear magnetic resonance and fluorescence polarisation. PLA interacts with phospholipids in a similar manner to other intrinsic proteins. For bilayers in the fluid state, the fatty-acyl chain static order, as measured by deuterium NMR, is slightly increased in the presence of the protein, except at very high PLA concentrations. Phosphorus NMR reveals some perturbation of the phospholipid polar group by PLA, but to a smaller degree than occurs with other intrinsic proteins. An increase in static order above tc (the onset temperature for gel-to-fluid transition) is also detected by infrared spectroscopy. Studies using steady-state polarisation of diphenylhexatriene fluorescence indicate that the microviscosity of the bilayer increases as a function of the protein mole fraction. From these data an estimation of the average number of lipids perturbed per protein monomer has been made, and a figure of 37 phospholipid molecules determined. The data are compatible with a picture of a hydrophobic polypeptide, perturbing the phospholipids close to it, but allowing rapid (greater than 10(4) s-1) exchange with all the lipid molecules in the system.

Apoproteins↗
PubMed1988

Fourier transform infrared spectroscopic studies on gastric H+/K+-ATPase.

Suspensions of membrane-bound H+/K+-ATPase in both H2O and 2H2O were investigated using Fourier transform infrared (FT-IR) spectroscopy. Second-derivative techniques were used to reveal the overlapping bands in the 1800-1500 cm-1 region. Analysis of the amide I band shows that the protein component contains substantial amounts of both alpha-helical and beta-sheet structures. Addition of 10 mM KCl to a suspension in 2H2O does not significantly affect the amide I band, indicating that the E1-E2 conformational transition of the enzyme, induced by K+, does not involve a gross change in protein secondary structure. Analysis of the amide II band in the spectra of suspensions in 2H2O shows that inhibition of the enzyme with omeprazole increases the rate of 1H-2H exchange, indicating an increase in conformational flexibility. Furthermore, an additional feature at 1628 cm-1 in the spectra of the inhibited samples in 2H2O could either support a conformational change or arise from a vibrational mode of omeprazole in its enzyme-bound form. The frequency of the band due to the symmetric stretching vibrations of the methylene groups of the lipid acyl chains increases steadily with increasing temperature indicating that there is no co-operative melting process in the lipid component of the membrane over the temperature range 9-50 degrees C. For comparison, FT-IR studies on aqueous suspensions of Na+/K+-ATPase were also carried out. These show that the protein components in the Na+/K+- and H+/K+-ATPases have similar secondary structures.

Adenosine Triphosphatases↗
PubMed1988

A study of the structure of human complement component factor H by Fourier transform infrared spectroscopy and secondary structure averaging methods.

Fourier transform infrared spectroscopy was used to investigate the secondary structure of human complement component factor H in H2O and 2H2O buffers. The spectra show a broad amide I band which after second-derivative calculations is shown to be composed of three components at 1645, 1663, and 1685 cm-1 in H2O and at 1638, 1661, and 1680 cm-1 in 2H2O. The frequencies of these components are consistent with the existence of an extensive antiparallel beta-strand secondary structure. The exchange properties of the amide protons of factor H as measured in 2H2O buffers are rapid and lead to an estimate of NH proton nonexchange that is comparable with those for small globular proteins. Human factor H is constructed from a linear sequence of 20 short consensus repeats with a mean of 61 residues in each one. To investigate the secondary structure further, secondary structure predictions were carried out on the basis of an alignment scheme for 101 sequences for these repeats as found in human factor H and 12 other proteins. These predictions were averaged in order to improve the reliability of the calculations. Both the Robson and the Chou-Fasman methods indicate significant beta-structural contents. Residues 21-51 in the 61-residue repeat show a clear prediction of four strands of beta-structure and four beta-turns. A structural model based on antiparallel beta-strands in the secondary structure is proposed and discussed.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗