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S J Forster

Publications and source records attributed to S J Forster.

12 recordsLinked to original sources
PubMed1994

Expression of foreign genes in mammalian cells using an antibody fusion system.

An expression system is described whereby a gene product is expressed fused to an antibody Fab fragment to form an antibody-like molecule. The antigen binding function of the original antibody is retained and the foreign gene replaces the CH2 and CH3 regions of the heavy chain. The fusion protein is secreted as if it were an antibody, and can be purified using the antigen-binding function of the Fab-like part of the molecule. In principle, any open reading frame can be expressed and it is not necessary to develop an individual purification scheme, or any analytical reagents such as antibodies, for the expressed protein, as both these functions can be performed by the Fab part of the fusion protein. In practice, the nature of the nonantibody part of the fusion influences the efficiency of expression and secretion, and detailed guidance is given on trouble-shooting and maximizing expression.

Amino Acid Sequence↗
PubMed1994

Efficient generation of a reshaped human mAb specific for the alpha toxin of Clostridium perfringens.

We have used the technique of antibody reshaping to produce a humanized antibody specific for the alpha toxin of Clostridium perfringens. The starting antibody was from a mouse hybridoma from which variable (V) region nucleotide sequences were determined. The complementarity-determining regions (CDRs) from these V regions were then inserted into human heavy and light chain V region genes with human constant region gene fragments subsequently added. The insertion of CDRs alone into human frameworks did not produce a functional reshaped antibody and modifications to the V region framework were required. With minor framework modifications, the affinity of the original murine mAb was restored and even exceeded. Where affinity was increased, an altered binding profile to overlapping peptides was observed. Computer modelling of the reshaped heavy chain V regions suggested that amino acids adjacent to CDRs can either contribute to, or distort, CDR loop conformation and must be adjusted to achieve high binding affinity.

Amino Acid Sequence↗
PubMed1989

1988 public awareness survey on AIDS and condoms in Uganda.

This report presents the results of a survey conducted between February and April 1988 to ascertain Ugandans' perception of AIDS as a problem, their knowledge of the disease and how it is spread, the resultant change in their sexual behaviour and their knowledge of, and attitudes towards, condoms. Two hundred and four people (98 women, 106 men) were interviewed from three locations; Kampala (an area with a high incidence of AIDS), Kabale, a town in central Kigezi, and villages in North Kigezi (both relatively low incidence areas). The main points to emerge are: (1) all the respondents were aware of the disease; (2) only 3.6% of respondents mentioned AIDS of their own accord as a problem for Uganda; (3) those in Kampala were most knowledgeable and men in all three areas were generally more informed than women; (4) change in behaviour was more pronounced in those who had known an AIDS victim personally; (5) 100% of men and 79% of women had heard of condoms but only eight men (9.4%) and one woman (1.0%) used condoms regularly for the prevention of AIDS, and (6) there was, nonetheless, a degree of willingness to use condoms once informed that they could reduce the risk of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Tumour basement membrane laminin in adenocarcinoma of rectum: an immunohistochemical study of biological and clinical significance.

Well-defined basement membrane laminin was seen in 98/158 (62%) rectal adenocarcinomas stained by an immunoperoxidase method. Only 27 (28%) patients with laminin-positive tumours developed distant metastases, compared with 39 (65%) patients with laminin-negative carcinomas. The corrected 5-year survival rates for patients with laminin-positive and laminin-negative tumours were 65% and 23%, respectively. Twenty-five out of 30 (83%) well-differentiated adenocarcinomas and only 3/15 (17%) poorly differentiated tumours contained basement membrane laminin, with moderately differentiated carcinomas showing intermediate laminin status (70/110, 64%, laminin positive). Forty-three of 60 (72%) of laminin-negative tumours had metastasized to regional lymph nodes. These data suggest that laminin may be a marker for differentiation. However, laminin status yields information about tumour behaviour which is not confined to stage and grade, and multivariate analysis shows that it is a better indicator of prognosis than tumour grade as assessed by conventional histology. Although laminin status alone is a less useful predictor of prognosis than Dukes' stage, a patient with a laminin-positive adenocarcinoma of rectum is 2.7 times as likely to survive 5 years than a patient with a laminin-negative tumour. Assessment of laminin status, together with Dukes' stage is, therefore, commended as a more precise and objective indicator of prognosis than histological degree of differentiation in colorectal carcinoma.

Adenocarcinoma↗
PubMed1984

Catalysis by protein disulphide-isomerase of the assembly of trimeric procollagen from procollagen polypeptide chains.

Type-I procollagen, 14C-biosynthetically labelled, was reduced under denaturing and non-denaturing conditions. Reoxidation to disulphide-linked trimers occurred with non-denatured chains in the presence of an oxidant system containing oxidized and reduced glutathione. Dimeric intermediates were not detected. This reoxidation was accelerated by homogeneous beef liver protein disulphide-isomerase.

Animals↗
PubMed1984

Laminin and fibronectin in rectal adenocarcinoma: relationship to tumour grade, stage and metastasis.

Using an immunoperoxidase procedure, we have examined the distribution of laminin and fibronectin in normal human large intestinal mucosa and in 50 cases of rectal adenocarcinoma for which extensive clinical follow up was available. In normal tissue, laminin staining was largely restricted to basement membranes, including that underlying the epithelial cells, whereas fibronectin was found in both basement membranes and surrounding connective tissue. In rectal carcinomas, basement membrane-like staining for laminin associated with tumour cells was found in only 27 out of the 50 cases studied. Statistical analysis showed that the presence of laminin-containing basement membranes was correlated with low histological grade (well-differentiated tumours), but not with stage (progression through the bowel wall and the development of lymph node metastases) and, in a highly significant way, with a reduced incidence of distant metastases and increased patient survival. Although fibronectin was found in tumour cell basement membranes where these were present, it was also found in the stroma of all 50 tumours. There was no apparent correlation between the presence of stromal fibronectin and grade, stage or development of metastases. Finally, attention is drawn to some of the technical difficulties in detecting basement membrane antigens in formalin-fixed tissue, the material most frequently available for retrospective study.

Adenocarcinoma↗
PubMed1982

The fibrinolytic effects of anaesthesia.

The fibrinolytic effects of six different anaesthetic agents were studied in 36 patients undergoing abdominal hysterectomy. Fibrinolytic activity was measured by dilute whole blood and euglobulin clot lysis times. Concentrations of plasminogen, fibrinogen and fibrin degradation products were also determined. Significant enhancement of fibrinolytic activity, measured as a decrease in clot lysis time, was seen during anaesthesia and surgery with all agents studied. Halothane produced the least effect and the greatest increase in fibrinolytic activity was seen during trichloroethylene anaesthesia. Lumbar extradural anaesthesia also consistently produced enhancement of fibrinolysis. The reasons for these results and their clinical implications are discussed.

Adult↗
PubMed1980

Protein disulphide-isomerase activity in chick-embryo tissues. Correlation with the biosynthesis of procollagen.

Protein disulphide-isomerase activity was determined in homogenates of chick-embryo tissues. Activities were highest in tissues active in procollagen synthesis and were maximal at the developmental stage of maximal procollagen synthesis. These variations in protein disulphide-isomerase activity correlate closely with those previously observed for protocollagen hydroxylase activities.

Animals↗