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C H Holmes

Publications and source records attributed to C H Holmes.

At least 37 records · Page 2Linked to original sources
PubMed1992

Complement regulatory proteins at the feto-maternal interface during human placental development: distribution of CD59 by comparison with membrane cofactor protein (CD46) and decay accelerating factor (CD55).

The complement (C) regulatory proteins decay-accelerating factor (DAF, CD55) and membrane cofactor protein (MCP, CD46), which control C3 convertases, together with CD59, an inhibitor of the membrane attack complex (MAC), were found to be present in the developing human placenta from at least 6 weeks of gestation until term. Immunostaining revealed differences in the distribution of these proteins on the fetally derived trophoblast epithelium, especially in early placentae which contain trophoblast populations of diverse proliferative potential and differentiation status. Expression of all three proteins occurred on the terminally differentiated syncytiotrophoblast epithelium covering chorionic villi and which is in direct contact with maternal blood. CD59 was also expressed on the underlying villous cytotrophoblast cells and on their extra-villous derivatives. These two populations showed differential expression of the C3 convertase regulators. Villous cytotrophoblast cells expressed MCP but were largely devoid of DAF. Proliferation of this population to generate extra-villous cytotrophoblast cell columns was associated with both an increase in DAF expression and a decrease in MCP expression. Throughout placental development, expression of DAF appeared to be lower than that of MCP and CD59 as assessed by solid-phase binding assays on isolated trophoblast membranes. Early placentae were also found to contain both DAF+ and DAF- chorionic villi. Conversely, expression of CD59 appeared comparatively high and transcripts for CD59 were found to be much more abundant than those for DAF in purified trophoblast cells. C regulatory proteins appear to play an important role throughout gestation in protecting the fetally derived human conceptus from maternal C. The differential expression patterns of the proteins on trophoblast may reflect differences in requirement for specific functional activities at different locations within the placenta.

Antigens, CD↗
PubMed1992

Complement and pregnancy: new insights into the immunobiology of the fetomaternal relationship.

Recent studies have revealed that human trophoblast expresses three membrane-bound proteins which function specifically to regulate the activity of complement. These proteins are already known to be widely distributed in normal adult tissues where they protect host cells from damage resulting from the fortuitous deposition of activated complement components. Their activities are focused at two distinct steps in the complement pathway. Decay accelerating factor (DAF, CD55) and membrane co-factor protein (MCP, CD46) act at the level of the C3 convertase enzymes which activate C3 to C3b. A further protein, CD59, directly regulates the formation and function of the terminal cytolytic membrane attack complex (MAC) by specifically interacting with C8 and C9. These proteins appear to play an important role in the maintenance of normal human pregnancy. DAF, MCP and CD59 are all expressed where trophoblast surfaces are in contact with maternal blood and tissues and expression occurs from at least 6 weeks of gestation. The semi-allogeneic human conceptus therefore appears to be effectively protected from maternal complement-mediated damage arising either from alternative or classical pathway activation or in a bystander fashion following a response to microbial infection in the mother. Complement regulatory protein deficiency disorders with clinically demonstrable consequences especially in terms of haemolytic disease are known to exist and have proved valuable in establishing the biological role of these proteins in vivo. The demonstration of this new family of immunoregulatory proteins on trophoblast raises important questions about the potential involvement of these products in pregnancy pathologies.

Complement C3↗
PubMed1991

New monoclonal antibodies in CD44 and CD58: their use to quantify CD44 and CD58 on normal human erythrocytes and to compare the distribution of CD44 and CD58 in human tissues.

The cell-surface glycoproteins CD44 and CD58 are involved in cell adhesion reactions. In this paper 12 monoclonal antibodies in CD44 and two in CD58 are described. Competitive binding assays using CD44 antibodies identified three distinct epitope groups. Antibodies in Group 1 and, with one exception (BRIC 214), antibodies in group 2, but not antibodies in Group 3, recognized epitopes that are sensitive to reduction and to trypsin or chymotrypsin treatment of intact erythrocytes, and so these epitopes probably reside on the N-terminal disulphide-bonded domain of CD44. Antibodies in CD44 did not inhibit the binding of CD58 antibodies to erythrocytes or vice versa. Quantitative binding studies using radioiodinated IgG measured 1888-5592 copies of CD44 and 1772-3290 copies of CD58 on normal erythrocytes. Similar measurements with radioiodinated Fab fragments gave values of 6508-10,450 (CD44) and 3457-7622 (CD58). Immunocytochemical studies indicated that CD44 is much more widely expressed in non-haemopoietic tissues than CD58. Comparison with previously described CD44 antibodies suggests that antibodies in our Group 1 encompass Hermes 2 and that those in Group 2 encompass Hermes 1. All the CD44 antibodies gave weakened reactions with Lu(a-b-) erythrocytes of the In(Lu) type by one or more methods. BRIC 214 and antibodies in epitope Group 3 were used to demonstrate that CD44 on these variant cells gives membrane-bound trypsin and chymotrypsin cleavage fragments of similar molecular weight to those obtained with normal erythrocytes.

Antibodies, Monoclonal↗
PubMed1990

Preferential expression of the complement regulatory protein decay accelerating factor at the fetomaternal interface during human pregnancy.

The expression of decay accelerating factor (DAF) was investigated in human fetal and extra-fetal tissues using a panel of mAb directed against different epitopes on the DAF molecule. By immunostaining, extensive reactivity was observed on the placental trophoblast epithelium and this was confined exclusively to sites of direct contact with maternal blood and tissues at the fetomaternal interface. Within the fetus, by contrast, very little staining was observed especially on hemopoietic cell populations in the developing liver. The antibodies identified a component of 70,000 m.w., comigrating on SDS-PAGE with red cell DAF, on isolated trophoblast membranes and an apparently quantitative increase in the expression of DAF was observed during placental development. Northern analysis using a DAF cDNA clone revealed 1.5-, 1.6-, and 2.2-kb mRNA transcripts typical of DAF in mRNA prepared from whole term placentae and from purified trophoblast cells. DAF appears to be preferentially expressed at the fetomaternal interface during development and may function specifically to inhibit amplification convertases formed at this site either directly or indirectly as a result of maternal complement activation. This molecule may play an important role in protecting the semiallogeneic human conceptus from maternal C-mediated attack.

Antibodies, Monoclonal↗
PubMed1989

Differential expression of the receptors for epidermal growth factor and insulin in the developing human placenta.

The detailed cellular distribution of epidermal growth factor (EGF) receptors and insulin receptors during the development of the human placenta was examined. We show that EGF receptors are expressed by villous cytotrophoblast cells in first trimester human placentae. However, where these cells proliferate to form extravillous cytotrophoblast cell columns, there is a dramatic decrease in EGF receptor expression. There is no such differential expression of insulin receptors on this cell population. In contrast, both EGF-and insulin-receptors are present throughout gestation on the microvillous membrane of the terminally differentiated and non-proliferative syncytiotrophoblast although, at term, EGF-but not insulin-receptors are also found on the basolateral membrane of this epithelium. We further show that EGF receptors isolated from first trimester and term human placentae have functional tyrosine kinase activities but differ in their extent of glycosylation. These results suggest that EGF receptors probably play several distinct functional roles in these epithelial cells depending on their proliferative capacity and differentiation status.

Adenosine Triphosphate↗
PubMed1989

Discrimination between normal and malignant hepatocytes in man by the monoclonal antibody RL23/36: comparison with the Ca1 and 791T/36 monoclonal antibodies.

The monoclonal antibody RL23/36 has been shown to discriminate normal from malignant hepatocytes in man. In frozen sections of liver tissue from 25 Thai patients without hepatocellular carcinomas, the antibody reacted strongly and preferentially with hepatocytes. Reactivity with 7 hepatocellular carcinomas was invariably abnormal, being totally absent in 5 and partially lost in 2. This discrimination was superior to that achieved with Ca1 and 791T/36 monoclonal antibodies. In 2 cases of hepatocellular carcinoma, binding of RL23/36 to associated apparently non-malignant hepatocytes was abnormal, being absent in one and partially lost in the other. These data show that RL23/36 detects an antigenic determinant which is lost during malignant transformation of human hepatocytes, sometimes before the development of frank malignancy.

Animals↗
PubMed1988

Expression of class I and II major histocompatibility complex antigens in Wilms' tumour and normal developing human kidney.

The Wilms' tumour is a solid childhood tumour of the kidney, consisting of blastema, tubules and mesenchyme. Embryonic tumours, such as Wilms', may arise as a result of a developmental disturbance in differentiation. The expression of class I and II major histocompatibility complex (MHC) antigens was investigated on 6 Wilms' tumours and related to that in the developing human kidney in this immunohistological study, using a panel of monoclonal antibodies. The Wilms' tumour blastemal cells were class I MHC antigen negative, but differentiated structures were positive. Class II MHC antigens were not observed in Wilms' tumours. In the developing human kidney class I MHC antigen expression was observed on glomeruli from 8 weeks and on tubules from 13 weeks gestational age. Class II MHC antigen expression was observed on glomeruli from 11 weeks and on tubules from 13 weeks gestation. These results suggest that the blastemal cells within the Wilms' tumour may reflect an early stage of development with respect to the expression of MHC antigens.

Adult↗
PubMed1986

Patterns of reactivity of the monoclonal antibody 791T/36 with different tumour metastases in the liver.

Reactivity of the monoclonal antibody 791T/36 with secondary malignant deposits has been investigated in frozen sections of 74 human liver biopsy specimens. There was no reactivity with hepatocytes but in some instances binding to fibrous tissues and in one case to portal tract lymphocytes was observed. Sections from 9 biopsy specimens contained malignant deposits. In seven of these 791T/36 bound either to malignant cells or to pseudoacinar contents (3 colorectal adenocarcinomas; 1 probable pancreatic adenocarcinoma; 1 medullary cell carcinoma of thyroid; 1 oat cell carcinoma of bronchus and 1 deposit of nodular sclerosing Hodgkins Disease). Two undifferentiated tumours (1 gastric adenocarcinoma and 1 oat cell bronchial carcinoma) showed no antibody binding. The histological pattern of reactivity previously reported with primary tumours appears to be similar in secondary deposits. A wider range of tumours than recognised hitherto binds 791T/36. Whether the binding to fibrous tissue seen in some instances is sufficient to cause diagnostic uncertainty when 791T/36 is used for scanning requires further investigation.

Adenocarcinoma↗
PubMed1984

Flow cytometric analysis of proflavine uptake into normal rat hepatocytes and cells arising during AAF-induced hepatocarcinogenesis.

The uptake of the fluorescent drug proflavine was measured in suspensions of hepatocytes from normal and carcinogen (2-acetylaminofluorine, AAF)-fed rats by flow cytometry. Drug uptake into hepatocytes from carcinogen-fed animals was consistently lower than that into hepatocytes from normal animals. Isolated nuclei, prepared from the livers of normal and AAF-fed rats showed similar proflavine uptake. Drug uptake into hepatocytes from AAF-fed animals, however, was increased by prior exposure to a metabolic inhibitor. Thus, differences in drug uptake may reflect changes in the cell membrane, together with an alteration in the metabolic integrity of the cells. The uptake of drug in hepatocytes from AAF-fed rats was uniformly low within each cell preparation. However, drug uptake varied not only between tumours arising in the livers of these animals but also within each tumour cell preparation. This study indicates that flow cytometry can provide an effective means for analysing drug uptake into cell populations arising during hepatocarcinogenesis.

2-Acetylaminofluorene↗
PubMed1984

Monoclonal antibodies reacting with normal rat liver cells as probes in hepatocarcinogenesis.

A series of four monoclonal antibodies was raised against suspensions of normal adult WAB/Not rat hepatocytes. An immunoperoxidase-staining technique was used to examine the distribution of determinants detected by these antibodies on frozen sections of fetal, neonatal, adult, and regenerating liver and on a range of 4-dimethylaminoazobenzene-induced liver lesions, including a panel of 32 primary liver carcinomas. Three of the antibodies were directed against hepatocytes, while a fourth antibody stained stromal elements within the liver. The determinants detected by the anti-hepatocyte monoclonal antibodies arose in a specific sequence during normal liver development and, when assessed in conjunction, characterized several phenotypes associated with stages in normal hepatocyte differentiation. These same antibody-defined phenotypes were expressed by the primary liver carcinomas, and the distribution of phenotypes among the tumors revealed a heterogeneity which was not evident from a conventional morphological classification. Primary liver tumors expressed a total of four antibody-defined phenotypes, whereas gamma-glutamyl transpeptidase-positive foci of hepatocytes and neoplastic nodules expressed, respectively, only one or 2 antibody-defined phenotypes. We suggest that monoclonal antibodies directed against normal liver cell components may provide a means to establish lineage relationships between cell populations involved in hepatocarcinogenesis.

Animals↗
PubMed1983

A monoclonal antibody reactive with human hepatocytes.

A monoclonal antibody, RL23/36, reacting preferentially with a determinant expressed on normal human hepatocytes is described. Use of an immunohistochemical technique on frozen sections from a range of 75 human liver biopsy specimens revealed that the determinant detected by RL23/36 was not expressed on hepatocytes from a number of patients with biopsy-proven liver disease. Although a normal staining pattern was observed in 28 of 29 biopsy specimens from patients with no evidence of liver disease, the antibody did not bind to hepatocytes in some cases of chronic active hepatitis (2/13), alcoholic liver disease (2/9), haemochromatosis (1/1), cirrhosis (1/2) and liver metastases (2/8). Furthermore, as in a previous study undertaken in the rat, the antibody failed to bind to tumour cells in the single human hepatoma observed in this study. These results suggest that further studies using RL23/36 may shed light on the pathogenesis of a number of liver diseases, including primary hepatocellular carcinoma.

Animals↗
PubMed1982

Expression of a monoclonal antibody-defined liver-associated antigen in normal rat hepatocytes and hepatocellular carcinoma cells.

In order to examine changes in the expression of normal cellular antigens during hepatocarcinogenesis, we have developed and characterized a monoclonal antibody detecting an antigen which is particularly associated with adult rat hepatocytes. The antibody showed no reactivity with a range of freshly-prepared normal syngeneic adult rat cell types, but showed strong reactivity with hepatocytes derived from several rat strains in antibody binding tests. Immunoperoxidase staining of sections of normal rat liver showed that the antigen was distributed throughout hepatocytes within the liver, but did not stain cells other than hepatocytes. The antigen detected by this monoclonal antibody was not detectable on a number of transplanted and primary dimethylaminoazobenzene-induced hepatomas. Preliminary data indicated that this monoclonal antibody may be suitable for use in flow cytofluorimetric sorting of mixed populations of normal and tumour cells, allowing the investigation of cell phenotypes during hepatocarcinogenesis.

Animals↗
PubMed1977

In vitro studies on the effects on granular gland secretion in Xenopus laevis skin of stimulation and blockade of alpha and beta adrenoceptors of myoepithelial cells.

Secretion from the granular glands of Xenopus laevis skin was stimulated by alpha-adrenergic agonists, an effect which was blocked by alpha-adrenergic antagonists and inhibited by beta-adrenergic agonists, db-cAMP and diazoxide. The inhibition by isoprenaline and salbutamol, but not that by diazoxide, was blocked by a beta-adrenergic antagonist. It is concluded that the myoepithelial cells surrounding the secretory compartment of the granular glands bear alpha and beta adrenoceptors, and that the beta receptors comprise, or at least include beta2 receptors.

Adrenergic alpha-Agonists↗
PubMed1976

Location of flap margin after suturing.

Facial and lingual flaps were reflected on 23 patients who required an apically positioned flap procedure. Immediately after suturing, the distance from the flap margin to the crest of the alveolar process was recorded by routine pocket probing techniques. Root coverage was about 2 mm, significantly greater than the coverage previously recommended.

Alveolar Process↗
PubMed1972

No more cavities.

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Dental Caries↗