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M Till

Publications and source records attributed to M Till.

63 records · Page 4Linked to original sources
PubMed1988

An assay that predicts the ability of monoclonal antibodies to form potent ricin A chain-containing immunotoxins.

In this report, we describe an assay for screening monoclonal antibodies for their cytotoxic potential as ricin A chain-containing immunotoxins. The assay involves treating cells with dilutions of the test antibody followed by a Fab fragment of a secondary antibody coupled to ricin A chain ("indirect assay"). The cytotoxicity of the indirect assay is compared to that of the direct assay where the monoclonal antibody is coupled to ricin A chain. Indirect and direct assays were carried out using 14 antibodies and a panel of 8 human and mouse cell types. The two assays showed virtually 100% correlation. The indirect assay, therefore, predicts the potency of a given monoclonal antibody to make an effective immunotoxin and should be useful in screening monoclonal antibodies for use as immunotoxins.

Antibodies, Monoclonal↗
PubMed1987

Redesigning nature's poisons to create anti-tumor reagents.

Immunotoxins are conjugates of cell-reactive antibodies and toxins or their subunits. In this report, the chemistry, biology, pharmacokinetics, and anti-tumor effects of first generation immunotoxins; the preparation of improved second generation immunotoxins that display greater anti-tumor efficacy; and the role of genetic engineering in creating third-generation immunotoxins are discussed.

Animals↗
PubMed1987

Modulation by enkephalin analogues and neuroleptics of apomorphine-induced stereotypy and turning behaviour in rats.

The aim of the present investigation was to examine which areas of the brain might mediate the anti-apomorphine action of some opioids, which were found previously to be active upon subcutaneous application. As the first step, the substances were injected intracerebroventricularly or into the nucleus accumbens, a mesolimbic region which is rich in dopamine, and the inhibition of stereotypy induced by apomorphine was quantified. In a separate group of animals (rats with unilateral lesion of the nigra) the antagonism of turning behaviour elicited by apomorphine was measured. Substances examined were morphine, a mu-selective opiate; D-Ala2,Nle5-enkephalin sulphonic acid (ES), a delta-selective opioid peptide; D-Met2,Pro5-enkephalinamide (EA), a highly potent but non-selective opioid; and two dopamine receptor blockers, haloperidol and chlorpromazine, for comparison. Examining the antagonism of turning behaviour induced by apomorphine, the order of potency was EA greater than haloperidol greater than morphine greater than ES approximately equal to chlorpromazine if injections of the substances were intracerebroventricular and EA greater than morphine much greater than haloperidol approximately equal to ES much greater than chlorpromazine when administered into the nucleus accumbens. The order of potency for the suppression of stereotypy induced by apomorphine was EA much greater than haloperidol greater than morphine greater than ES greater than chlorpromazine upon intracerebroventricular application and EA much greater than haloperidol greater than morphine ES greater than chlorpromazine if injected into the nucleus accumbens. The data indicate that endogenous opioids might inhibit the activity of dopamine in brain through the nucleus accumbens.

Animals↗
PubMed1986

Effects of D-Met2, Pro5-enkephalinamide on pain tolerance and some cognitive functions in man.

The effects of D-Met2, Pro5-enkephalinamide (EA) on pain tolerance and some cognitive functions have been examined in healthy male volunteers. Dihydrocodeine (DC) was used as reference substance. Applying the submaximum effort tourniquet technique EA (10 mg SC) was found to elevate the pain threshold similarly to DC (20 mg SC). Neither DC nor EA impaired the performance in the symbol cancellation test, which quantitates the intensity of attention. In this assay rather a slight improvement was detected. in addition the short-term memory performance (Wechsler test) was also improved by EA and DC. No alteration was seen in the word fluency test, an indicator of long-term (semantic) memory. The data show that EA not only improves pain tolerance but some of its mental effects are similar to those of a classical morphine congener DC.

Adult↗
PubMed1980

Antiglobulin antibody in the sera of contacts of children with leukaemia.

Healthy adults (parents, neighbours, and hospital staff) in close contact with children with leukaemia were found to have a high incidence of positive latex agglutination antiglobulin tests (probably an IgM antiglobulin antibody). This may explain a previous report of a high incidence of IgM anti-EB virus antibodies in parents of leukaemic children, which our results did not confirm (IgM antiglobulin, reacting with IgG anti-EB virus, could have been misinterpreted as IgM anti-EB virus). The antiglobulin antibody probably represents a nonspecific response to an infective agent. Other hospital staff, including those exposed to nonleukaemic children with infections, had a much lower incidence of the antibody, and it may represent a response to the leukaemic process itself, rather than to the infections to which such children are prone. Some leukaemic children have a similar antibody.

Adolescent↗
PubMed1979

Family studies in acute leukaemia in childhood: a possible association with autoimmune disease.

Medical histories of themselves and their first-degree relatives were obtained from parents of 82 leukaemic children (54 acute lymphoblastic (ALL), 28 acute myeloblastic (AML)) and from control couples matched for age. The possibility of a primary familial immunological abnormality as an aetiological factor in childhood leukaemia was suggested by binding some infections significantly more frequently reported in parents than in controls, but more strongly supported by the finding of a significantly (P less than 0.02) increased prevalence of disorders associated with autoimmunity (but not of other conditions such as peptic ulceration, infective hepatitis, tuberculosis or malignancy) amongst members of ALL families compared to those of controls. Analogy with Down's syndrome and the strain of NZB mice, in which diminished T-cell function is associated with autoimmune disease and lymphoid neoplasia, is discussed. Varicella and herpes zoster occurred respectively in 2 ALL mothers during their pregnancies involving the patients and in none of the other 388 pregnancies here reported. This supports previous evidence that antenatal varicella infections may be of aetiological importance in some cases of ALL.

Adolescent↗
PubMed1978

Dermatoglyphics in childhood leukaemia: a guide to prognosis and aetiology?

The results of analysis of the dermatoglyphics of 152 children with acute lymphoblastic leukaemia (ALL) (and the first-degree relatives of 54 of them) contrast with those of 31 children with acute myeloblastic leukaemia (AML) (and the first-degree relatives of 25 of them). In ALL our findings suggest that neither genetic susceptibility nor an environmental factor, effective during the early antenatal period, is of aetiological importance; but the response to treatment, assessed as length of first remission, was found to be related to the amount of fingertip pattern. This may have clinical application. In AML there is evidence of a genetically determined factor carrying a high risk of the development of the disease, in that a member of each of 5 different families of the 25 studied bore a rare hypothenar pattern, compared with none in 75 control families. No dermatoglyphic features were of prognostic significance in AML.

Adolescent↗
PubMedDate not supplied

A submicroscopic unbalanced subtelomeric translocation t(2p;10q) identified by fluorescence in situ hybridization: fetus with increased nuchal translucency and normal standard karyotype with later growth and developmental delay, rhombencephalosynapsis (RES).

Reaching an accurate diagnosis in children with mental retardation associated or not with dysmorphic signs is important to make precise diagnosis of a syndrome and for genetic counseling. A female case with severe growth and development delay, dysmorphic features and feeding disorder is presented. Antenataly, the fetus was observed to have increased nuchal translucency and a slight hypoplastic cerebellum. A standard karyotype was normal. RES and a submicroscopic unbalanced subtelomeric translocation t(2p; 10q) were demonstrated after birth. We show that within the framework of a collaborative approach, a concerted research of submicroscopic subtelomeric rearrangements should be performed in case of mental retardation associated with facial dysmorphic features, and when other etiologies or non-genetic factors (iatrogenic, toxic, infectious, metabolic...) have been ruled out.

Cerebellum↗