The influence of DNA repair on neurological degeneration, cachexia, skin cancer and internal neoplasms: autopsy report of four xeroderma pigmentosum patients (XP-A, XP-C and XP-D)

BACKGROUND: To investigate the association of DNA nucleotide excision repair (NER) defects with neurological degeneration, cachexia and cancer, we performed autopsies on 4 adult xeroderma pigmentosum (XP) patients with different clinical features and defects in NER complementation groups XP-A, XP-C or XP-D. RESULTS: The XP-A (XP12BE) and XP-D (XP18BE) patients exhibited progressive neurological deterioration with sensorineural hearing loss. The clinical spectrum encompassed severe cachexia in the XP-A (XP12BE) patient, numerous skin cancers in the XP-A and two XP-C (XP24BE and XP1BE) patients and only few skin cancers in the XP-D patient. Two XP-C patients developed internal neoplasms including glioblastoma in XP24BE and uterine adenocarcinoma in XP1BE. At autopsy, the brains of the 44 yr XP-A and the 45 yr XP-D patients were profoundly atrophic and characterized microscopically by diffuse neuronal loss, myelin pallor and gliosis. Unlike the XP-A patient, the XP-D patient had a thickened calvarium, and the brain showed vacuolization of the neuropil in the cerebrum, cerebellum and brainstem, and patchy Purkinje cell loss. Axonal neuropathy and chronic denervation atrophy of the skeletal muscles were observed in the XP-A patient, but not in the XP-D patient. CONCLUSIONS: These clinical manifestations and autopsy findings indicate advanced involvement of the central and peripheral nervous system. Despite similar defects in DNA repair, different clinicopathological phenotypes are seen in the four cases, and therefore distinct patterns of neurodegeneration characterize XP-D, XP-A and XP-C patients

INHIBITION STEPS IN SULFONAMIDE BACTERIOSTASIS OF ESCHERICHIA COLI

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INACTIVITY OF PTEROYLGLUTAMIC ACID AND LEUCOVORIN IN OVERCOMING SULFONAMIDE GROWTH INHIBITION OF ESCHERICHIA COLI

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STUDIES ON THE ACCUMULATION OF 4-AMINO-5-IMIDAZOLE CARBOXAMIDE IN ESCHERICHIA COLI

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Inhibition steps in sulphonamide bacteriostasis

The activity of several compounds, structurally unrelated to p-aminobenzoic acid, in reversing growth inhibition of Escherichia coli by sulphonamides, was explained by Shive and Roberts as due to their being products of enzymes associated with p-amino-benzoic acid. Using increasing concentrations of sulphanilamide, these authors showed that it inhibits sequentially the synthesis of methionine and xanthine by the organism. Winkler and de Haan extended this study to higher concentrations of the inhibitor, and reported further involvement of serine and thymine (the latter, interchangeably with pteroyl glutamic acid) in that order in the p-aminobenzoic acid action; further addition of valine was stimulatory to growth

Reversal by folic acid of penicillin action on growth and on pentose nucleic acid synthesis in Lactobacillus casei

1. Cells of L. casei grown in presence of penicillin are found to contain decreased amounts of PNA, DNA being unaffected. 2. PGA by itself and, more effectively, in presence of vitamin B12 exerts protection against the inhibitory action of the antibiotic on growth as well as on PNA formation

Reversal of sulphonamide action in Escherichia coli (B<SUB>12</SUB> auxotroph) by vitamin B<SUB>12</SUB>

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