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Biomedical subjects

M R Price

Publications and source records attributed to M R Price.

At least 109 records · Page 6Linked to original sources
PubMed1990

A comparison of prescribing patterns and consequent costs at Alexandra Health Centre and in the private fee-for-service medical aid sector.

About 25% of private health expenditure in South Africa goes on medicines. This compares with about 6% in the public sector, and about 12% in the UK. A major factor contributing to these differences is the prescribing practices of physicians, and generic prescribing in particular. This is a preliminary study to assess the savings that might be possible by altering prescribing practices. A sample of 528 scripts from Alexandra Health Centre (AHC) was analysed to calculate the average number of items per script and the average cost per script. In order to make the costs comparable to expenditure on medicines in the private fee-for-service sector, the scripts from AHC were costed as if they had been dispensed by private pharmacies--including dispensing fees, packaging costs and general sales tax. Since AHC clinicians generally prescribe medicines in the prepacked quantities, nothing is added to the costs for 'broken bulk'. However, as is the practice at AHC, cheaper therapeutic equivalents were substituted wherever possible. The number of items per script in the fee-for-service sector was 17% higher than at AHC, and the cost per item at AHC was one-quarter that in the private sector. Various explanations are offered including the possible incomparability of the case mix in the two sectors and the relative quality of care. However, the difference is so large that it is concluded that generic substitution, prepackaging and the use of treatment protocols by the clinicians are the major contributing factors.

Costs and Cost Analysis↗
PubMed1990

The 1983 distribution of hospitals and hospital beds in the RSA by area, race, ownership and type.

This study used published data to analyse the 1983 distribution of hospitals and hospital beds in South Africa by 'race', geographical area, type of hospital (academic, specialist, general or other) and the nature of ownership (e.g. state, for-profit). Hospitals and hospital beds were found to be inequitably distributed. Overall bed ratios were 150 whites per bed compared with 260 blacks/Asians/coloureds per bed. The distribution of beds by geographical area was 130 people per bed for urban whites, 260 for rural whites and 150, 460 and 300 for urban, rural non-'homeland', and 'homeland' blacks/Asians/coloureds respectively. These differentials are inefficient and unjust, and should be regularly documented to spur their decline. The continued collection of population group information from health service users is required to monitor changes in 'race' disparities. The analysis of distribution by ownership and type suggested that only the public sector is able to provide a hospital service with the appropriate balance of all levels of care for the entire population; but within this sector the dominant position of tertiary care needs to be re-examined. The study highlighted the absence of adequate information on health care resource allocation and utillisation. Appropriate studies in these areas are required and consideration should be given to unifying the planning and management of all hospital resources.

Black or African American↗
PubMed1990

Detection of polymorphic epithelial mucins in the serum of systemic breast cancer patients using the monoclonal antibody, NCRC-11.

Serum from patients with systemic breast cancer was found to contain elevated levels of polymorphic epithelial mucin (PEM) as detected using an immunoradiometric assay employing the monoclonal antibody NCRC-11. PEM was partially purified from pooled sera from these patients and the complex, polymorphic, high-molecular-mass (greater than 400 kDa) mucin was identified by sodium dodecylsulphate/polyacrylamide gel electrophoresis, Western blotting and immunostaining with the NCRC-11 antibody. Serial serum samples from 16 patients with metastatic breast cancer were assayed for circulating PEM defined by the monoclonal antibody NCRC-11. The clinical course of disease in these patients was assessed independently as progressive, static or responsive. Increasing NCRC-11 antigen levels correlated with disease progression in 6/7 patients, and decreasing antigen levels correlated with an objective response to treatment in 5/6 patients. Measurement of NCRC-11-defined PEM antigen in patients undergoing therapy for metastatic breast cancer showed an overall accuracy of 75%.

Antibodies, Monoclonal↗
PubMed1990

Immunological and structural features of the protein core of human polymorphic epithelial mucin.

The protein core of high mol. wt polymorphic epithelial mucin (PEM--approximately 400 kDa glycoprotein) which is associated with breast carcinomas, consists of a repeating 20 amino acid peptide motif [Gendler et al. (1988) J. biol. Chem. 263, 12,820-12,823]. Monoclonal antibodies C595 (anti-urinary mucin) and NCRC-11 (anti-breast carcinoma cells), and other antibodies against human milk fat globule membranes, were found to recognize determinants present within this 20 amino acid peptide. A model of the peptide was developed based on hydropathicity and structure prediction calculations and these indicated that the repeated structure is dominated by a hydrophilic domain of seven amino acids, extending into two flanking beta turns. NMR analysis of the 20 amino acid peptide was undertaken to probe the secondary structure. Epitope mapping experiments involving solid phase synthesis of overlapping heptapeptides in the repeat unit identified the minimum structures for antibody binding as Arg-Pro-Ala-Pro and Arg-Pro-Ala for the C595 and NCRC-11 antibodies, respectively. These determinants were found within the predicted hydrophilic turn region domain of the peptide. The epitopes for six other PEM-reactive monoclonal antibodies were also determined to reside within the predicted hydrophilic turn domain. This evidence is in accord with the disposition of this region of the PEM peptide core being at the exterior of the glycoprotein where it would be accessible to antibody recognition and binding events.

Amino Acid Sequence↗
PubMed1990

Assessment of four monoclonal antibodies as serum markers in breast cancer.

Four monoclonal-antibody-defined serum markers (CA15-3, HMFG1, HMFG2 and NCRC-11) were examined in five groups of subjects: controls, benign breast disease and stage I/II, stage III and metastatic breast cancer. None of the markers were significantly elevated in primary breast cancer (i.e. stage I/II or stage III) compared with controls or patients with benign breast disease. These markers therefore have no role in screening or in the diagnosis of primary breast cancer. CA15-3, HMFG2 and NCRC-11 were significantly increased in the patients with metastatic breast cancer (P less than 0.001), indicating a potential use in the diagnosis of symptomatic metastases. In patients with metastases, sequential changes in CA15-3 correlated significantly with clinical response to therapy. Thus CA15-3 is a powerful marker of response and in combination with other markers, may provide an objective measurement of response to therapy in patients with advanced breast cancer.

Adult↗
PubMed1990

C595--a monoclonal antibody against the protein core of human urinary epithelial mucin commonly expressed in breast carcinomas.

Urinary mucins which express determinants for the anti-breast carcinoma monoclonal antibody, NCRC-11 (IgM), closely resemble the mammary mucins found in milk fat globules and carcinomas. An IgG3 monoclonal antibody, C595, was prepared against urinary mucins isolated on a NCRC-11 antibody affinity column, and this 'second generation' antibody was shown to have a very similar pattern of reactivity to the original NCRC-11 antibody. By immunohistology, the profile of reactivity of both antibodies with tumour and normal tissue specimens was virtually identical. Both antibodies reacted with epithelial mucins isolated from breast tumours or normal urine using an NCRC-11 antibody affinity column, although the antibodies were unreactive with other antigen preparations. Heterologous immunoradiometric assays ('sandwich' tests) confirmed that NCRC-11 and C595 epitopes were co-expressed on the same molecule. C595 antibodies inhibited the binding of radiolabelled NCRC-11 antibodies to antigen, suggesting that the two epitopes were in close topographical proximity. The protein core of the mammary mucins has recently been shown to consist predominantly of a repeated 20 amino acid sequence (Gendler et al., 1988). Peptides with this complete sequence and small fragments were synthesised, and the C595 antibody was found to recognise an epitope within this repeat. The ability to identify and synthesise monoclonal antibody-defined determinants, as well as those in the adjacent or overlapping sequences within the protein core of epithelial mucins, is viewed as a strategy for facilitating the production of antibodies of new and novel specificity to complement the panels of existing anti-breast cancer reagents.

Antibodies, Monoclonal↗
PubMed1990

Polymorphic epithelial mucin from the sera of advanced breast cancer patients--isolation and partial characterisation.

The anti-breast carcinoma monoclonal antibody (MAb), NCRC-11 defines a polymorphic epithelial mucin (PEM) which is elevated in the circulation of advanced breast carcinoma patients. Here we describe the purification and partial characterisation of this component from patients' sera and its use in the production of a second generation MAb, C568 (IgM). Pooled sera was fractionated by immunoaffinity and size-exclusion chromatography and the purity of preparations assessed by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting. Serum-derived PEM shows a similar pattern of electrophoretic mobility to PEM isolated from primary breast tumour tissue and migrates as several bands in 4% SDS polyacrylamide gels (Mr greater than 400,000). The epitope expression of PEMs isolated from either source is also similar, with both bearing topographically distinct determinants for several anti-mucin MAbs. The immunoreactivities of antibodies C568 and NCRC-11 were unaffected by boiling, reduction and alkylation, or by enzyme desialylation of PEM. Periodate oxidation and proteolytic digestion have suggested that the antigenic determinant for C568 is carbohydrate in nature whilst that of NCRC-11 is peptidic. In accord with the mucinous nature of the molecule, serum-derived PEM is susceptible to reductive beta-elimination, elutes in the void volume of a Sepharose CL-4B column and has a buoyant density of 1.45 g ml-1.

Antibodies, Monoclonal↗
PubMed1990

A phase I/II study of trichosanthin treatment of HIV disease.

Trichosanthin, a ribosomal inhibitor protein, blocks HIV replication in lymphocytes and macrophages. This agent was used to treat 51 patients with advanced HIV disease in a dose-escalation study in which three injections were administered over a 9-21-day period in a dose range of 10-30 micrograms/kg per injection. The maximum tolerated dose was estimated to be 30 micrograms/kg. Reversible but severe fatigue and myalgias were the major dose-limiting side-effects; mild leucocytosis and elevations in serum transaminases were noted and were reversible. Non-dose-related reversible mental status changes were seen in six patients and were considered to be associated with the drug. This was usually manifest as dementia, but progressed to coma in two patients. This reversed, but the sequelae resulted in death in one patient. Decreases in serum p24 antigen levels were noted 1 month after the first infusion in 10 of 18 patients who entered the study with elevated levels; one converted to negative. Values usually remained low to the end of the study period (2 months). In those patients with CD4+ cell levels greater than 50 x 10(6) cells/l significant decreases in sedimentation rate and increases in CD4+ cell numbers were also noted. These changes were found at all dose levels but only in patients receiving three infusions.

Adult↗
PubMed1989

Human monoclonal anti-idiotypic antibody to the tumour-associated antibody 791T/36.

A human monoclonal antibody, 105AD7, was produced by fusion of a mouse/human heteromyeloma cell line with lymphocytes from a patient previously injected with mouse monoclonal antibody 791T/36 for tumour immunoscintigraphy. The 105AD7 hybridoma has been in continuous culture for more than 12 months, producing a human monoclonal IgG1 which binds to 791T/36 (IgG2b) and its IgG2a class switch variant, but not a range of other monoclonal mouse immunoglobulins. In quantitative flow cytometric assays, 105AD7 was shown to block the binding of fluorescein-labelled 791T/36 to its target gp72 antigen at the surface of tumour cells, but not the binding of 228, an anti-carcinoembryonic antigen (CEA) monoclonal antibody to CEA. Tests with purified 105AD7 antibody demonstrated a stoichiometric high-affinity interaction between 105AD7 and 791T/36. Thus 105AD7 is a human anti-idiotypic antibody which binds at or very close to the binding site of 791T/36, and as such is a candidate for anti-idiotypic immunization of cancer patients.

Antibodies, Anti-Idiotypic↗
PubMed1988

Potentiation of anti-carcinoembryonic antigen immunotoxin cytotoxicity by monoclonal antibodies reacting with co-expressed carcinoembryonic antigen epitopes.

The initial step in ricin A-chain (RTA)-immunotoxin-mediated cell cytotoxicity involves binding to the target cell Ag through the antibody moiety. One of the factors influencing this is the affinity of the antibody component for the target cell Ag. Multiple epitopes on carcinoembryonic Ag have been mapped providing a range of mAb of known specificity. These have been used to show that the cytotoxicity of an immunotoxin containing RTA conjugated to an anti-carcinoembryonic Ag mAb (228-RTA) is potentiated by mAb recognizing different epitopes. The potentiating antibodies also increased the level of target cell binding of antibody 228. Cross-linking of cell bound antibody was not involved because monovalent fragments of a potentiating antibody were effective. The potentiating antibodies modified the binding affinity of 228 antibody increasing the t1/2 of antibody at the tumor cell surface. This increased the dwell time of cell bound antibody and using conjugates of 228 linked to albumin-tetramethylrhodamine it was shown to enhance conjugate endocytosis. These investigations indicate that enhanced antibody affinity leads to increased endocytosis of bound immunoconjugate and potentiates cytotoxicity.

Adjuvants, Immunologic↗
PubMed1988

Epitopes of carcinoembryonic antigen (CEA) defined by monoclonal antibodies.

Of 15 anti-CEA monoclonal antibodies, the first 8 were reactive only with CEA, while the remaining 7 antibodies reacted with epitopes commonly expressed on CEA and the normal cross-reacting antigen, NCA. Separate and distinct, conformation-dependent (i.e. susceptible to reduction and alkylation), CEA-associated epitopes were identified using antibodies 1, 2 and 3. Antibodies 4 to 7 defined a series of conformation-independent epitopes which were topographically closely related on the CEA molecule. Antibody number 8 reacted with a separate determinant found on CEA but not NCA, and this also was resistant to reduction and alkylation. Antibody number 9 defined an epitope which was commonly expressed on CEA and NCA. This epitope was conformation-dependent and was the most sensitive to NaIO4. The remaining antibodies, 10 to 15, which also reacted with CEA and NCA, defined an immunodominant region of these molecules since the 6 epitopes were clearly closely related, but not necessarily identical. The findings presented establish a rational basis for the selection of combinations of anti-CEA antibodies for diagnostic and therapeutic purposes.

Animals↗
PubMed1987

Mapping of monoclonal antibody-defined epitopes associated with carcinoembryonic antigen, CEA.

Six immunoglobulin G monoclonal antibodies reactive with carcinoembryonic antigen (CEA) were evaluated with respect to parameters implicated in their potential diagnostic application and use as tumor targeting agents for cytotoxic drugs or plant or bacterial toxins. Antibody reactivity with surface antigens of the MKN-45 gastric tumor cell line was demonstrated by flow cytofluorimetry. In a subcellular membrane binding assay, each antibody reacted preferentially with membranes isolated from colorectal tumor tissue in comparison with their reaction with membranes from adjacent, apparently normal colonic mucosa. Three of the antibodies (NCRC-23, C228, and 11.285.14) reacted specifically with CEA with little or no reaction with the cross-reacting antigen, NCA. The remaining three antibodies (C24, C161, and C198) were reactive with both CEA and NCA. Analysis of the epitopes defined by these antibodies was performed by competitive binding inhibition assays evaluating the capacity of unlabeled antibodies to compete with 125I-labeled antibodies in their binding to CEA. In addition, double determinant or 'sandwich' radioimmunoassays were employed to examine the coexpression of epitopes on CEA molecules. These studies permitted an epitope map to be constructed which describes the coincidence, overlapping, or independent expression of both CEA specific epitopes and epitopes shared between CEA and NCA. The map may be employed for the selection of antibodies for diagnostic and therapeutic use.

Antibodies, Monoclonal↗
PubMed1987

Identification of a monoclonal antibody-defined breast carcinoma antigen in body fluids.

The monoclonal antibody NCRC-11 defines antigens associated with secretory glandular epithelia as well as most epithelial malignancies. These components have been identified in, and isolated from, normal body fluids including urine and skim milk. The immunoadsorbent purified antigens from urine and milk were very similar to those purified from breast and ovarian carcinomas; by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS PAGE) and immunoblotting, NCRC-11 antibody-binding antigens from all sources were of high apparent molecular weight (greater than 400 kD) with the major component(s) present as a single band or a doublet. Also, by analysing epitope profiles, all purified antigen preparations were shown to react in a characteristic manner with a panel of monoclonal antibodies which were originally produced against human milk products or materials from tumours. Since it was shown that NCRC-11 antigens were released from tissues in a soluble form, the possibility that these antigens might represent a diagnostic marker for breast cancer was evaluated. The findings obtained indicated that NCRC-11 antigens were elevated in the serum of advanced breast cancer patients in comparison to healthy control females, so that access to the circulation was available to these products released from the tumour but not to those released from normal epithelia.

Aged↗
PubMed1987

Biochemical and immunochemical analysis of a breast carcinoma associated antigen defined by the monoclonal antibody NCRC-11.

NCRC-11 is an anti-human breast carcinoma monoclonal antibody which defines a high molecular weight glycoprotein antigen (greater than 400 kD) and the expression of this antigen in breast carcinomas correlates with patient survival (Ellis et al.--Brit. Med. J., 290: 881-883, 1985). The antigen has been purified from detergent extracts of breast carcinomas by immunoadsorbent chromatography, and shown to be a wheat germ agglutinin-binding glycoprotein, which is susceptible to proteolysis with pepsin or papain although NCRC-11 antibody binding is unaffected by heat (100 degrees C for 5 min) or neuraminidase treatment. In addition to its presence in tumours, the NCRC-11 antigen is also a product of specialized normal epithelia (being particularly associated with luminal surfaces of secretory epithelia), although in healthy individuals it is not found in the circulation. However, in breast cancer patients, the breast tissue architecture is disrupted sufficiently by the developing tumour to allow products from the tumour to have access to the circulation. Thus, NCRC-11 antigens have been identified in breast cancer patients' serum both by immunoblotting techniques and by sandwich radioimmunoassay. The findings indicate that the NCRC-11 antigen has potential as a diagnostic and prognostic marker in breast cancer.

Antibodies, Monoclonal↗
PubMed1986

Measurement of tumour reactive antibody and antibody conjugate by competition, quantitated by flow cytofluorimetry.

Binding of unlabelled monoclonal antibody preparations has been assessed by competition at saturation with fluorochrome labelled homologous antibody for binding to antigen bearing target cells. The extent of competition was measured by quantitative flow cytofluorimetry, and simple mathematical procedures have been developed to allow the interpretation of competition data in terms of antibody binding activity. In the system studied, non-specific (non-competitive) fluorescence was minimal, but an iterative method to calculate its contribution to the measured signal is given. This approach has the advantage that the antibody preparation to be tested does not need to be labelled or modified; this is particularly important when evaluating the binding activity of therapeutic antibody conjugates. Comparison with a well characterized standard antibody preparation provides a rapid, sensitive and accurate quality control procedure. This test is also simple to perform, requiring only the mixing of labelled and unlabelled antibodies with target cells, a single incubation, followed by analysis without washing of the target cells.

Animals↗