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Biomedical subjects

M Wall

Publications and source records attributed to M Wall.

At least 73 records · Page 4Linked to original sources
PubMed1994

Therapeutic efficacy of camptothecin derivatives against human malignant melanoma xenografts.

Camptothecin (CPT) and some of its derivatives are currently used in several clinical studies with patients bearing leukaemias, lymphomas, and malignancies of various solid tissues. Therefore, it is important to establish parameters and conditions that will allow the drugs to exhibit maximal anti-cancer effectiveness with minimal toxic effects. We tested several water-insoluble CPT derivatives for their ability to inhibit growth of human melanoma tumours xenografted in nude mice. We found that anti-tumour effectiveness and drug-induced toxicity depended on (a) the CPT derivative; (b) the drug dose administered; (c) the mode of administration; and (d) the scheduling of drug administration. For all practical purposes, oral administration of the CPT derivative, 9-nitrocamptothecin, has produced the best overall results.

Animals↗
PubMed1993

Functional consequences of engagement of the T cell receptor by low affinity ligands.

The mechanisms involved in TCR antagonism by Ag analog/MHC have been analyzed. A detailed structure-activity relationship study indicated that modification of any of the major T cell contact residues of the peptide molecule can yield a powerful antagonist. It was also shown that as the analog structure increased in similarity to the Ag, the capacity to antagonize Ag-TCR interaction increased up to the point that the analogs themselves became antigenic. These data strongly suggest an affinity-related mechanism whereby a certain affinity is required for signaling through the TCR, and that below this level there can be sufficient affinity to engage the receptor such that triggering does not occur and antagonism can be detected. Taking advantage of this information, antagonist peptides active down to the 10 nM range were engineered. Thus, this approach demonstrates for the first time a rational approach to designing effective, selective low m.w. compounds with high potential in treatment of allergies and autoimmune diseases.

Amino Acids↗
PubMed1992

DRB1*0301 molecules recognize a structural motif distinct from the one recognized by most DR beta 1 alleles.

The DR3-restricted peptide, MT 65 kDa 3-13, was used to develop a DR3-specific binding assay. The binding activity detected was strictly pH-dependent, in that it was optimal in the pH 4 to 5 range, and no activity was detected at neutral pH. By means of affinity chromatography purifications and the use of DR3-transfected fibroblasts, it was shown that no cross-reactivity exists at the level of DR52a molecules, thus allowing use of only partially purified DR3/DR52a mixtures in high throughput binding assays. The immunologic relevance of the assay established was also verified by examining the correlation between DR3 restriction and binding for a panel of DR-restricted peptides. When the structural requirements for peptide DR3 interactions were further examined by using panels of analogues of two different epitopes (Myo 132-151 and TT 830-843), it was found that DR3 molecules recognized a peptide motif distinct from the one recognized by the other major DR beta 1 alleles.

Alleles↗
PubMed1992

Longitudinal analysis of adolescent growth of ladino and Mayan school children in Guatemala: effects of environment and sex.

The rate of growth in height and the timing of adolescent growth events are analyzed for two samples of Guatemalan children. One sample includes Mayan school children, 33 boys and 12 girls between the ages of 5.00 to 17.99 years, living under poor conditions for growth and development. The second sample includes ladino children, 78 boys and 85 girls of the same age range, living under favorable conditions for growth. The Preece-Baines model I function is used to estimate mean values for rates and timing of childhood and adolescent growth events for the two groups. Significant statistical contrasts (t-tests) of these means show Mayan boys reach the age of "take-off" (TO; the onset of the adolescent growth spurt) 1.45 years later, achieve peak height velocity (PHV) 1.68 years later, and continue growing for about 2.0 years longer than do the ladino boys. Despite the Mayan boys' increased duration for growth they grow significantly more slowly than the ladinos. Mayan boys are 6.60 cm shorter than ladinos at the age of TO and are estimated to be 7.71 cm shorter than the ladinos at adulthood. Mayan girls reach the age of TO 0.93 years later than do the ladina girls, but the two groups do not differ in the age at PHV or the age at adulthood. The mean height of Mayan girls is significantly less than that of ladinas at the age of TO (6.5 cm), and this difference increases to an estimated 11.14 cm at adulthood. Possible causes of these ethnic and sex-related differences in amounts and rates of growth are discussed in relation to hypotheses about the genetic and environmental determinants of human development.

Adolescent↗
PubMed1992

Liver function tests in persons receiving anticonvulsant medications.

Liver function tests were carried out in 206 adults and children taking anticonvulsants to ascertain the prevalence of biochemical abnormalities in asymptomatic patients. It was observed that serum gamma-glutamyl transpeptidase was elevated in 74.6% of patients, alkaline phosphatase in 29.7% and alanine aminotransferase in 25.2% of cases. These figures are similar to those previously reported in the literature and probably reflect hepatic enzyme induction by the anticonvulsants. It is suggested that there is no value in the routine performance of liver function tests in patients with epilepsy. However, such patients should be informed of the symptoms of hepatic dysfunction and asked to report for liver function tests should they have such symptoms.

Adolescent↗
PubMed1992

High affinity for class II molecules as a necessary but not sufficient characteristic of encephalitogenic determinants.

A direct binding assay specific for IAs molecules has been developed and its immunological relevance validated by examining, for a panel of nine different synthetic peptides, the correlation between their capacity to bind purified IAs and to inhibit IAs-restricted antigen presentation. The IAs assay thus developed has then been used to study the IAs binding affinity of a set of overlapping peptides spanning the entire myelin basic protein (MBP). It was found that the encephalitogenic MBP region corresponds to peptides with high MHC binding affinities. Other regions of the MBP that have not been described as being pathogenic in the context of IAs molecules have also been found to be high IAs binders, suggesting that variables other than MHC affinity are also involved in determining the pathogenic potential of self-derived determinants.

Amino Acid Sequence↗
PubMed1991

On the interaction of promiscuous antigenic peptides with different DR alleles. Identification of common structural motifs.

We have investigated the interaction between DR1 molecules and the two antigenic peptides, tetanus toxoid 830-843 and hemagglutinin 307-319, previously known to bind most DR alleles (degenerate binding) and to be recognized by the same T cell clones in the context of different DR alleles (promiscuous T cell recognition). The DR1 affinity of these two peptides was compared with that of two other different T cell epitopes (pertussis toxin 30-42 and ragweed allergen Ra3 51-65). It was found that degeneracy and promiscuity were associated with high affinity interactions, whereas binding and T cell selectivity were associated with weaker interactions. Thus, the selectivity of DR-peptide interactions, as is commonly observed with the antibody molecule, appears to be inversely correlated to affinity. Several singly substituted analogs of the hemagglutinin 307-319 determinant have also been tested for capacity to bind various DR alleles (DR1, DR2, DR5, and DR7). The results obtained suggest that this determinant may bind the different DR alleles in a similar orientation. Similar conclusions were reached when the interaction between the tetanus toxoid 830-843 determinant and three different DR alleles (DR1, DR2, and DR7) was studied following the same experimental approach. When crucial DR-binding residues of the two peptides were compared, it was found that they were very similar in both chemical nature and spacing in the peptide primary structure, suggesting that the two peptides may bind DR in a very similar orientation. Finally, a putative motif has been derived and shown to be present in a majority of the DR binders tested, but only in a minority of the non-DR binding peptides.

Alleles↗
PubMed1991

Indomethacin-sensitive monocyte killing defect in a child with disseminated atypical mycobacterial disease.

A child with disseminated disease due to Mycobacterium avium had progressive disease in spite of 4.5 years of therapy with multiple antimicrobial agents selected on the basis of in vitro sensitivity testing of her organism. A defect in monocyte bactericidal activity was detected which was corrected in vitro by exposure of the patient's monocytes to indomethacin and normal serum. Indomethacin therapy resulted in normalization of monocyte bactericidal activity and striking, albeit temporary, clinical improvement.

Blood Bactericidal Activity↗
PubMed1991

Symptoms and disease associations in idiopathic intracranial hypertension (pseudotumor cerebri): a case-control study.

To identify the symptoms and coexisting medical conditions associated with idiopathic intracranial hypertension (IIH), we administered an 83-item questionnaire at the time of diagnosis to 50 IIH patients and 100 aged-matched controls. Ninety percent of the IIH patients were women; the mean age was 33. Obesity and recent weight gain were much more common among patients than controls. Symptoms most commonly reported by IIH patients were headache (94%), transient visual obscurations (TVO) (68%), and intracranial noises (ICN) (58%). Daily occurrence of these symptoms was much more common among patients than controls. Controls also reported these and other IIH symptoms, but at lower frequencies. Several conditions previously associated with IIH were no more common in patients than controls including iron deficiency anemia, thyroid disease, pregnancy, antibiotic intake, and use of oral contraceptives. We conclude that previous studies of IIH, mostly uncontrolled and retrospective, have underestimated the frequency of symptoms in IIH patients and reported chance and spurious associations with common medical conditions and medications. The profile of a young obese woman with headaches and either TVO or ICN should alert the clinician to the diagnosis of IIH, especially when the symptoms occur daily.

Adolescent↗