Biomedical subjects
Publications and source records attributed to M R Harris.
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Atomic coordinates for pig insulin in the cubic crystal have been refined by reciprocal-space methods to an R factor of 0.173 for data between 10.0 and 1.7 A resolution with structure-factor amplitudes greater than two standard deviations. Stereochemical parameters for the refined model are close to standard values and the estimated error in the positions of well-ordered atoms is about 0.1 A. Residues directly involved in the formation of the exact (crystallographic) cubic insulin dimer are oriented similarly to those in the non-crystallographic 2Zn insulin dimer. Other residues, which make different molecular contacts in the different crystal forms, have locally altered conformations. The cubic insulin molecule is significantly more similar to one of the two independent molecules in the 2Zn insulin dimer than the other. This more similar molecule is expected to be the more stable conformer.
It has been proposed that invariant chain (Ii), a nonpolymorphic, transmembrane glycoprotein found in noncovalent association with Ia molecules, may function to protect the Ia Ag-binding site from association with self-peptides during Ia synthesis. Selective binding of foreign antigenic peptides could then be allowed by the dissociation of Ii molecules from Ia in the appropriate intracellular compartment. In this study, we have examined the structure and intracellular trafficking patterns of a putative proteolytic product of Ii, p25. We found that p25 is a non-membrane-bound fragment of Ii with an N terminus beginning at Met98 of the Ii sequence. p25 is formed at a very early stage of Ii synthesis in the rough endoplasmic reticulum rather than in a post-Golgi Ag-processing compartment. We have also characterized a second Ii-related species, p28, which has not been reported previously. The p28 form of Ii, unlike p25, is generated under acidic conditions similar to those found during Ag processing.
Dosimetric and radiobiological studies were undertaken to investigate the potential enhancement in dose, dose distribution and cell killing effectiveness of 252Cf brachytherapy achievable when boron-10 enriched compounds are incorporated into simulated 252Cf brain implants. Thermal neutron distributions in a human head phantom containing a 252Cf source were measured by gold foil activation and calculated using a 1-dimensional transport code. This information was then used to modify measured event size distributions for 252Cf neutrons to determine the corresponding increase in dose and dose equivalent throughout the phantom. The addition of subtoxic levels of boron-10 to a typical 252Cf implant was found to significantly enhance both the absorbed dose and the high LET event frequency at distances of 3 to 5 cm from individual sources. Some unexpected geometric considerations are discussed. Reduced survival of cultured Chinese hamster cells correlated with the predicted increase in absorbed dose from the capture events with a concentration of about 60 micrograms 10B per ml in the culture medium. It was found that boron increased alpha (the "single-hit" parameter of the linear quadratic survival model) by 32% and decreased beta (the "double-hit" parameter) by 8%. The alpha/beta ratio increased to 4.34 Gy in the presence of boron, from 3.03 Gy in its absence. This translated to an 8% reduction in californium dose needed to effect 10% cell survival. It is concluded that there is a sufficiently high thermal neutron fluence present during californium brachytherapy for boron neutron capture dose augmentation to be feasible.
We have previously reported the complete sequence of the cDNAs corresponding to the alleles at the polymorphic loci (DRB1, DRB3, DQA1, DQB1) of the DRw11(5) cell line Swei. We now report the nucleotide and derived amino acid sequence of the alleles at the remaining two polymorphic loci, DPA1 and DPB1, from Swei, which types as DPw4b. Comparison of the DPw4b alpha sequence with previous DP alpha sequences indicates that it is identical to the DP alpha chains of DPw4 and DPw2. However, the DPw4b alpha cDNA encodes a unique 3' untranslated region that corresponds to sequences contained within the last intron of the DP alpha genomic gene. These results indicate that alternative splicing occurs within the Swei DP alpha RNA. Comparison of the DPw4b beta sequence with previously reported DP beta sequences indicates that the first domain is identical to the sequence of the DP beta chain derived from the Burkhardt (Burk) cell line, but that the second domain differs by two amino acids. In addition, a single amino acid difference from DPw2 at position 69 in the first domain of the DPw4b beta chain suggests that this residue is important in determining DP specificity. Furthermore, comparison with other DP beta DNA sequences suggests that variable regions occur at positions 8-11, 55-57, and 84-87.
We prospectively evaluated 71 nasoenteral feeding tube insertions in critically ill patients and found a 4% incidence of pulmonary complications. All pulmonary complications occurred in tracheally intubated patients. To prevent these complications, we developed an enteral feeding tube insertion technique using a 26-Fr red rubber catheter as an introducer for a 8-Fr feeding tube. This technique is easy to perform by hospital staff and well tolerated by patients. No pulmonary complications occurred in 31 subsequent feeding tube insertions.
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Inspection of preparations of H1, H1(0) and H5 histones made by extraction of whole tissues has shown that dimers and higher polymers of all three of these proteins are present. They may be formed by the cross-linking action of poly(ADP-ribose) chains which are linked to some of the protein molecules. Putative dimers and higher polymers were noted in preparations from various tissues and species. However, evidence is presented which suggests that production of these polymers is an artifact of precipitation during the preparation of the proteins, so the significance of the polymers is questionable.
A survey of H1o and H5-like proteins has been conducted through a range of higher and lower eukaryotic species. All mammals examined possessed H1o proteins, although in variable amounts, and the protein's structure was well conserved, though not invariant. The testis-specific histone Hlt (from rat) did not have an H1o-like structure and it appears that H1o does not occur in spermatocytes in any form. The results also show that Xenopus laevis contains H1o-like proteins, but lower, non-vertebrate eukaryotes (a crustacean, two fungi and a plant tissue) do not possess H1o or H5 proteins. The evidence suggests that H1o and H5 proteins may be considered as belonging to one family, distinct from H1 types. This H1o/H5 family may well be 'replacement histone' variants of H1. The results do not support suggestions of roles such as repression of DNA synthesis or of transcription for H1o/H5 proteins.
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We examined the antigen-presenting capacity of BCL1 tumor cells, which are capable of differentiating in vitro with respect to immunoglobulin synthesis/secretion under the influence of LPS. In vivo passaged BCL1 cells depleted of host cell contamination either by positive selection employing panning with anti-lambda reagents, or by elimination of latex-ingesting adherent cells, are capable of MHC-restricted antigen presentation to a GAT-immune T cell line. The BCL1 cells act as antigen-presenting cells when freshly explanted, but gradual loss of this function occurs, and cells cultured for 3.5 days cannot present antigen unless LPS is included during the culture period. BCL1 cells are equivalently Ia+ after the culture period with or without LPS stimulation. Other B cell lines capable of antigen presentation appear to express this trait constitutively, and the in vivo passaged BCL1 line is therefore unique among B cell lines in having antigen-presenting cell function that can be modulated. The data suggest that freshly explanted or LPS-cultured BCL1 cells are heterogeneous with respect to antigen-presenting capacity, and the basis for this heterogeneity is being sought. BCL1 offers an opportunity to study requirements for antigen presentation by B cells.
The histone H10 was examined from seven mammalian species. All tissues were shown to contain two subfractions of H10, except for those of rabbit, in which little or no H10 was found. The subfraction composition was compared quantitatively in different mouse and hamster tissues, with the conclusion that this composition is tissue-specific. It is proposed that the wide occurrence of H10, together with the evidence of no more or less than two subfractions wherever it occurs, and the tissue-specific nature of the ratio of subfractions, signify that these two subfractions have specific individual functions.
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