Biomedical subjects
Publications and source records attributed to D A Nelson.
L-Asparaginase-induced coagulation abnormalities were observed in all patients receivng this drug. All patients studied demonstrated low factor IX and fibrinogen levels and most (75%) had low levels of factor XI. Disturbances in other factors were much less frequent. Despite the presence of markedly abnormal coagulation studies, clinical bleeding was not observed.
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Chinchillas were trained with shock-avoidance procedures to discriminate or detect pure-tone frequency differences. Inital attempts at determining frequency-difference thresholds utilized a complex discrimination paradigm and a go-no-go response. Although discriminations of large frequency differences were obtained from chinchillas after considerable training, discriminations of small frequency differences could not be trained. Therefore, determinations of frequency-difference thresholds could not be made with the complex discrimination paradigm and the go-no-go response task. A simple detection paradigm, involving the detection of frequency alternation in an ongoing train of tone bursts proved to be a more successful technique. Frequency-alternation detection was quickly learned by six chinchillas, and frequency-difference thresholds were obtained with an adaptive sequential procedure. Psychometric functions were reconstructed from the threshold tracking data of chinchillas, and comparisons were made with differential frequency thresholds from cats and humans obtained by previous investigators. Differential frequency thresholds from chinchillas paralleled those from cats and were about twice as large. Differential frequency thresholds from humans were considerably smaller than from chinchillas, especially for low-frequency tones. When a constant detectability index was used to specify differential frequency sensitiviy in chinchillas, chinchilla and human differential sensitivity functions paralleled one another. Human differential sensitivity was about ten times better than that of the chinchilla.
The organization of proteins along DNA in chromatin of Saccharomyces cerevisiae (baker's yeast) was examined by analyzing the DNA and nucleoprotein products obtained after digestion of yeast nuclei with staphylococcal nuclease. Yeast DNA is digested in situ at regularly spaced cleavage sites about 160 base pairs apart. Nucleoprotein fragments were resolved and isolated by centrifugation on linear, 5-20% sucrose gradients. The predominant 11S component appears to be identical to chromatin "subunits" or "nucleosomes" isolated from higher eukaryotes, containing a 150-160 base pair length of DNA and approximately equimolar amounts of four proteins that coelectrophorese with calf histones H2A, H2B, H3, and H4, plus small amounts of three proteins that electrophorese similarly to H1 histones. Thus, the structural organization of the yeast genome is similar to that of more developed organisms, except for the smaller total repeat length. None of the yeast subunit proteins, including the possible H1 proteins, contains cysteine.
Zeta sedimentation ratios (ZSR) and modified Westergren erythrocyte sedimentation rates (ESR) were compared with an independent clinical assessment of disease activity in 100 patients with rheumatoid arthritis. The correlation between ZSR and ESR was good. Both methods correlated well with disease activity. The ZSR was more frequently elevated than the ESR in each category of disease activity, but the differences were slight. In addition to its practical advantages, the ZSR appears to be a satisfactory method for monitoring the activity of rheumatoid arthritis.
Two specific slow sedimenting nucleoprotein particles containing equimolar amounts of histones H2A and H2B and 38 or 49 base pair (bp) lengths of DNA have been isolated by centrifugation on sucrose gradients. The 3.4S particles containing 38 bp DNA and H2A+H2B thermally denature at 61 degrees, considerably higher than Proteinase K treated particles (44 degrees), but lower than 11S nucleosomes (76 degrees). Treatment with Proteinase K increases the circular dichroism of 3.4S particles at 280 nm by 63% and decreases the sedimentation coefficient to 2.1S. These results indicate that H2A and H2B are proximate along DNA in nucleosomes and alone can alter the optical activity and perhaps conformation of local regions of DNA.
DNA lengths in the structural repeat units of Chinese hamster ovary (CHO) and chicken erythrocyte chromatin were compared by analyzing the sizes of DNA fragments produced after treatment of nuclei with staphylococcal nuclease. The repeat length of CHO chromatin (173 +- 4 BP) is about 20 base pairs (BP) smaller than that of chicken erythrocyte chromatin (194 +- 8 BP). Repeat lengths of rat liver and calf thymus chromatin were found to be about 10 BP shorter than that of chicken erythrocyte chromatin. Thus significant variations occur in repeat units of chromatin of higher eukaryotes. These variations occur in the lengths of "spacer" (or "internucleosomal") DNA segments, not in "core particle" (or "nucleosomal") DNA lengths. The concept of spacer regions and the possible influence of H1 histones is discussed.
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The methods used by the Rehabilitation Unit of the Repatriation General Hospital, Daw Park, to involve relatives of stroke patients in the rehabilitation process are outlined. The use of group therapy techniques for relatives is described and the issues commonly encountered are discussed. The value of the group meetings for relatives and staff is emphasized.
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The zeta sedimentation ratio (ZRS) was evaluated and found to have advantages over the erythrocyte sedimentation rate (ESR). The normal range for the ZSR proved to be 41 to 54%. Elevated ESR's obtained with the modified Westergren technic were also associated with an increased ZSR, except when amenia spuriously elevated the ESR. Reproducibility after storage was slightly better for the ZSR than for the ESR, But for optimal results the test should be performed within two hours of phlebotomy. Increased concentrations od EDTA anticoagulant may falsely elevate the ZSR, especially if the ZSR is initially elevated.
Digestion of calf thymus chromatin with micrococcal nuclease produces a mixture of apparently well defined nucleoprotein fragments which have been partially resolved by sedimentation on linear (5-20%) sucrose gradients. Sedimentation patterns reveal a predominant peak at the 11S position, three slower components, which have not previously been reported, at the 3.4S, 5.3S and 8.6S positions, and three faster components at the 17S, 22S and 26S positions. DNA isolated from the 3S to 12S region of gradients has been resolved on polyacrylamide gels into nine to ten discrete components ranging from 47 to 156 base pairs in length. A nearly identical pattern of small DNA products was obtained from chromatin digested in intact nuclei. These data suggest that chromatin contains either several types of subunits or predominently a single type of subunit which can be asymmetrically cleaved at any one of four or more sites.
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