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Biomedical subjects

T D Bird

Publications and source records attributed to T D Bird.

189 records · Page 11Linked to original sources
PubMed1975

Monozygotic twins with Huntington's disease in a family expressing the rigid variant.

A set of male monozygotic twins concordant for Huntington's disease is described. The monozygosity of the twins and the diagnosis of Huntington's disease are well established. The twins are now age 30, and although the severity of their chorea differs, they have a similar degree of mental deficit. This family is of additional interest because the daughter of one of the twins has childhood Huntington's disease, and the mother of the twins had the adult-onset rigid variant of the disease. Such unusual families afford some insight into the variability of the clinical manifestations of this hereditary disease.

Diseases in Twins↗
PubMedDate not supplied

Effects of L-glutamate on viabilities of cultured diploid skin fibroblasts and lymphocytes. Increased toxicity not observed in Huntington's disease.

The toxicity of L-glutamic acid toward cultured fibroblasts and lymphocytes from age-matched, sex-matched controls, patients with Huntington's disease (HD) and patients with other diseases has been studied. In an initial non-blinded study, L-glutamic acid (15 mM) exerted a significant toxic effect on HD fibroblasts, decreasing viability by approximately 60% after 48 h exposure. The magnitude of the toxic effect on HD fibroblasts as a group was significantly different from the mean effect on the normal control group (P less than 0.003) and non-HD control group (P less than 0.004). However, there was variability in the sensitivity of a given fibroblast culture to L-glutamate. This toxic effect was also seen in several normal control and non-HD control fibroblasts. In a second blinded study using cultured fibroblasts from HD patients and age-matched, sex-matched controls, we were unable to distinguish between HD and control cultures. No difference in L-glutamate toxicity was observed between control and HD lymphocytes in short-term cultures. We conclude that the toxicity of L-glutamate is not specific for HD cells and that this experimental approach will be of little value in identifying cells from patients with HD.

Adult↗
PubMedDate not supplied

Evidence for etiologic heterogeneity in Alzheimer's disease.

We briefly describe the evidence for etiologic heterogeneity in Alzheimer's disease. Several different genetic and environmental factors may act separately or in combination to produce the AD phenotype. This potential heterogeneity presents special challenges to those attempting to identify specific genetic influences in the pathogenesis of AD.

Alzheimer Disease↗
PubMedDate not supplied

Intracellular calcium response is reduced in CD4+ lymphocytes in Alzheimer's disease and in older persons with Down's syndrome.

Abnormalities in intracellular free calcium ([Ca2+]i) regulation are likely to play a role in brain aging and have been described in cells from patients with Alzheimer's disease (AD). [Ca2+]i acts as a second messenger in transmembrane signaling and regulates diverse functions in many cell types. Therefore, abnormalities in [Ca2+]i response may have far-ranging effects. Using flow cytometric assay for [Ca2+]i, we examined whether mitogen-induced increases in [Ca2+]i are abnormal in CD4+ T-lymphocytes from patients with familial AD (FAD), other AD, and Down's syndrome (DS) compared to age-matched controls. We observed that the peak [Ca2+]i responses were significantly decreased in CD4+ cells from 6 FAD patients (59% of control), 34 other AD patients (69% of age-matched control), and 6 older persons with DS (> 25 years old, 47% of control), after stimulation with 10 micrograms/ml anti-CD3 monoclonal antibody (mAb). The number of CD3 receptors on T lymphocytes of the AD patients was not decreased. In contrast, lymphocytes from subjects with FAD, other AD and older DS patients had no decrease in response to phytohemagglutinin (30 micrograms/ml). CD3 and related classes of membrane receptors are present on many cells of the central nervous system. Therefore, receptor signaling defects via this receptor in T lymphocytes of AD patients may be relevant to the central nervous system pathology seen in AD and DS.

Adult↗
PubMedDate not supplied

Trypsin inhibitor activities of fibroblasts increase with age of donor and are unaltered in familial Alzheimer's disease.

Increasing evidence suggests that proteases and their inhibitors play an important role in the etiology of beta-amyloidogenesis and Alzheimer's disease (AD). It is not clear, however, which proteases and protease inhibitors are responsible for the amyloidogenic proteolysis. Candidates include alpha-1-antichymotrypsin, inter-alpha-trypsin inhibitor, and forms of beta-amyloid precursor protein (beta PP) bearing Kunitz protease inhibitor domains. As one approach to this question, we have determined the trypsin inhibitor activity of fibroblast-like cells from 10 familial AD subjects and 20 controls. The activity was quantitated by measuring remaining trypsin activity of reaction mixtures containing trypsin and cell lysates using a fluorogenic substrate and two physiologically distinct populations of fibroblasts: proliferating cells (grown in the presence of 16% serum) and quiescent cells (maintained in 0.1% serum). The remaining trypsin activities of crude protein extracts from proliferating and quiescent AD cultures were not significantly different from those of controls. Perhaps of more general interest to the biology of aging, however, was our finding that protease inhibitor activity increased with the age of the donor (p = 0.005).

Adult↗