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Biomedical subjects

C Rhodes

Publications and source records attributed to C Rhodes.

At least 19 recordsLinked to original sources
PubMed1992

Exclusion of human proteoglycan link protein (CRTL1) and type II collagen (COL2A1) genes in pseudoachondroplasia.

Patients with pseudoachondroplasia have a skeletal dysplasia with marked short stature. The most common cause of this condition is an autosomal dominant mutation, although autosomal recessive inheritance has been reported. Linkage to 2 cartilage-specific candidate genes, type II collagen (COL2A1) and proteoglycan link protein genes (CRTL1), was tested in 9 autosomal dominant families with pseudoachondroplasia. Tight linkage to these candidate genes was excluded with LOD scores for COL2A1 of -2.45 at theta = 0.05 and for CRTL1 of -7.28 at theta = 0.001. Discordant inheritance of the disease phenotype with each of these genes was also observed. Thus, these 2 candidate genes can be excluded as the cause of disease in these families.

Collagen↗
PubMed1992

The ratio of mouse insulin I:insulin II does not reflect that of the corresponding preproinsulin mRNAs.

Rats and mice both express two, non-allelic, insulin genes. In the rat the ratio of the two preproinsulin mRNAs closely matches that of the mature insulin peptides. The experiments reported here demonstrate that this is not the case in the mouse. The relative amounts of the two murine proinsulin RNAs were measured by an S1 nuclease assay. The ratio of preproinsulin I mRNA to preproinsulin II mRNA was 4:1 in RNA extracted from the pancreas of mice fed ad libitum or fasted for 72 h. A similar value was found in mouse islets of Langerhans after maintenance in tissue culture for 48 h at either 2.8 or 16.7 mM glucose. The ratio of insulin I:insulin II peptides, assessed by separating the two insulins using reversed phase high-performance liquid chromatography, was approximately 1:3 in both pancreas and islets. Thus in the mouse, unlike the rat, the ratio of the two insulin peptides does not reflect that of the two preproinsulin mRNAs.

Amino Acid Sequence↗
PubMed1992

Ca(2+)-regulated serine protease associated with the nuclear scaffold.

The nuclear scaffold (NS) is a proteinaceous network of orthogonally arrayed intermediate filament proteins, termed lamins, which is responsible for nuclear structure. Recent work has demonstrated that a subset of lamins A/C is proteolytically cleaved to produce an ATP-binding protein. This proteolytic cleavage is accomplished by a NS protease activity, which shows a considerable selectivity for lamins A/C and is stringently regulated by Ca2+ in vitro, suggesting that it might also participate in control of NS breakdown in various scenarios. Here, we identify the major NS protease as a novel serine protease with a predominantly chymotryptic-like substrate preference, and we show that even transient perturbations in cytosolic Ca2+ have significant effects on the NS protease activity. This NS protease activity shows extensive similarities to the multicatalytic proteinase complex. In addition to a potential role in control of NS breakdown at mitosis and/or under pathological conditions, this NS protease is also strategically located for other functions, such as inactivation of various oncogenic proteins or maturation-promoting factor.

Amino Acid Sequence↗
PubMed1991

Characterization of the promoter for the rat and human link protein gene.

We have isolated the 5'-end of the gene for the rat and human link protein by screening genomic libraries with oligonucleotides corresponding to the 5'-cDNA sequence. Several overlapping clones were isolated for the human link protein gene, while only one clone was obtained for the rat. All the clones contained a single exon of which the sequence was identical to the most 5'-end of the rat and human cDNAs. Transcription initiation sites for the rat link gene were identified by primer extension and S1 protection analysis using total RNA from the rat Swarm chondrosarcoma. Transcriptional initiation sites for the human link gene were determined by specific primer extension of RNA from human fetal cartilage. Comparison of 1500 bp of 5'-flanking sequence between the rat and human link protein genes showed strong sequence conservation near the start site of transcription with 80% overall identity. Analysis of the 5'-flanking regions also revealed a large inverted repeat consisting of repeating purine-pyrimidine, which has the potential to form left-handed Z-DNA. Transcriptional regulation of the link protein gene was studied by coupling either 7.0 kb or 0.85 kb of 5'-flanking rat DNA to the chloramphenicol acetyltransferase (CAT) gene followed by transfection into chick embryonic chondrocytes (CEC) and HeLa cells. Both constructs had considerable CAT activity in CEC cells and less activity in HeLa cells. Furthermore, inclusion of a DNA fragment from the first intron increased relative CAT activity in both of these cell types. The increased activity from the first intron was shown to be orientation independent in CEC. These results indicate the presence of positive cisacting regulatory elements in both the promoter and first intron of the rat gene for link protein.

Animals↗
PubMed1988

Alternative splicing generates two different mRNA species for rat link protein.

Previously we isolated a cDNA clone which encoded the carboxyl-terminal portion of the rat link protein (Doege, K., Hassell, J.R., Caterson, B., and Yamada, Y. (1986) Proc. Natl. Acad. Sci. U.S.A. 83, 3761-3765). Here we report the isolation of cDNA clones encoding the remainder of the protein. Sequence analysis revealed two classes of cDNA clones identical except for the occurrence of an additional internal nucleotide segment of 159 base pairs coding for 53 amino acids in one of the clones. Genomic clones were then isolated using the cDNA as a probe. Sequence analysis of genomic clones revealed that the internal 159-base pair cDNA segment was contained in a single exon. The protein sequence deduced from these two cDNAs were Mr = 44,779 (link 45) and Mr = 38,570 (link 39). Northern blotting of chondrosarcoma RNA revealed that both the alternate exon specific to link 45 and an exon common to both link 45 and 39 hybridized to the same size classes of link protein transcripts (1.5-5.5 kilobases), although link 45 transcripts are much less prevalent than link 39 transcripts. The link 39 sequence corresponds exactly with the predominant form of chondrosarcoma link protein. The similarity in size between link 45 and the larger form of link protein (LP1) observed in other species appears fortuitous.

Amino Acid Sequence↗
PubMed1988

Skin irritancy of commercially available alkyl ether sulphate surfactants: is there a difference between those with alkyl chains consisting of even or odd numbers of carbon atoms?

Various concentrations of commercially available alkyl ether sulphate surfactants with alkyl chains consisting of even or odd numbers of carbon atoms have been tested for their primary irritancy to rabbit skin in vivo. All six surfactants (2 with even and 4 with odd carbon number) produced skin irritation. The level of irritation showed dose-dependent increases in the concentration range 4-12% (w/w), with a plateauing of responses of moderate to severe irritation occurring between 12 and 24% (w/w). Recovery generally took 10-14 days to occur. There were no significant differences in the intensity or duration of response between surfactants with alkyl chains consisting of even and odd numbers of carbon atoms.

Alkanesulfonates↗
PubMed1988

The permeability of grafted human transplant skin in athymic mice.

Human skin has been transplanted onto athymic mice and its permeability properties assessed to see if this in-vivo model would be of benefit in predicting accurately absorption of drugs or toxic chemicals through human skin. The permeability properties of the skin alone, and grafted and athymic mouse skin were assessed by measuring in-vitro absorption of tritiated water and a permanently charged cationic penetrant, paraquat. The grafted skin and athymic mouse skin had similar permeability to the tritiated water. However, the grafted skin was less permeable to paraquat but was more permeable to it than normal human skin, indicating that although histologically, the transplanted skin appeared normal, its barrier properties were impaired. The model was not, therefore, useful for assessing human percutaneous absorption.

Animals↗
PubMed1988

Segments of amino acid sequence similarity in beta-amylases.

In alpha-amylases from animals, plants and bacteria and in beta-amylases from plants and bacteria a number of segments exhibit amino acid sequence similarity specific to the alpha or to the beta type, respectively. In the case of the beta-amylases the similar sequence regions are extensive and they are disrupted only by short interspersed dissimilar regions. Close to the C terminus, however, no such sequence similarity exist.

Amino Acid Sequence↗
PubMed1987

A quantitative assessment of pyrethroid-induced paraesthesia in the guinea-pig flank model.

Pyrethroids are known to induce cutaneous effects in man which are distinct from the classical irritation and vascular responses. These effects are characterised by transient facial burning and tingling sensations. The aetiology of this cutaneous effect is related to the ability of pyrethroids to produce trains of nerve impulses in afferent nerves by prolonging the opening of the neuronal sodium channel. The veratrum alkaloids which are structurally dissimilar to the pyrethroids are known to affect the sodium channel in a similar manner. Using the guinea-pig flank model which has been developed to study this cutaneous phenomenon we have constructed dose-response curves to three structurally related pyrethroids (permethrin, cypermethrin and deltamethrin) and to a mixture of veratrum alkaloids (veratrine). In addition we have examined the time course over which these chemicals elicit a response.

Animals↗
PubMed1987

Antiidiotypic antibodies to human major histocompatibility complex class I and II antibodies in hepatic transplantation and their role in allograft survival.

In order to evaluate the role of antiidiotypic antibodies to anti-MHC in human liver transplant recipients, serial serum samples obtained from 10 liver recipients both pre- and posttransplantation were analyzed for the development of HLA alloantisera inhibitory activity by a microcytotoxicity inhibition assay. Seven of the 10 recipients developed strong anti-anti-HLA activity during the immediate posttransplant period, which was able to block killing of a specific alloantiserum to class I MHC antigens (44-100%). Recipients' sera were also able to block class II alloantisera (HLA-DR8) cytotoxicity of B-lymphocytes. The inhibitory activity developed 10-15 days posttransplantation, was cyclical, and was present in the immunoglobulin fraction of the serum. One patient developed specific antibodies to anti-HLA-B7 and had no inhibition for alloantisera to HLA-B8,B17,B49 and B13. Another developed antibodies capable of blocking anti-HLA B44 (mismatched donor antigen) and also cytotoxicity of HLA-B17,B49 (crossreactive group), but showed no significant inhibition of HLA-B13,B8 and B7. One recipient, transplanted across strong (1:500 titer) antilymphocyte crossmatch, rejected the graft within 1 month and failed to develop any inhibitory antibodies to anti-HLA. Two other patients who lost their grafts within 2 months posttransplantation developed only minimal (11% and 16%) and transient inhibition. Immunoprecipitation of surface-labeled, mixed lymphocyte culture stimulated lymphocytes, with sera containing inhibitory antibodies, identified membrane components of approximate molecular weights of 54,43 and 17,000, suggesting T cell clonotypic structures. Thus, these studies provide support for the development of antiidiotypic antibodies to anti-MHC in human liver transplant recipients, which may play a regulatory role in the tolerance of allograft.

Antibodies, Anti-Idiotypic↗