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L Leonard

Publications and source records attributed to L Leonard.

14 recordsLinked to original sources
PubMed1992

Domains of cellular retinoic acid-binding protein I (CRABP I) expression in the hindbrain and neural crest of the mouse embryo.

We describe here the distribution of cellular retinoic acid-binding protein I (CRABP I) in the head of the early mouse embryo from day 8 to day 13 of gestation, using both in situ hybridisation to localise mRNA and immunocytochemistry to localise protein. The distribution of mRNA and protein was found to be identical. CRABP I first appeared in part of the presumptive hindbrain of the presomite embryo and then became localised to rhombomeres 2, 4, 5 and 6. The only other area of expression in the cephalic neuroepithelium was in a part of the midbrain roof. The neural crest and its mesenchymal derivatives, the branchial arches, expressed CRABP I and crest could be seen streaming from the neuroepithelium of individual rhombomeres into particular branchial arches. This suggested a fate map could be constructed describing the rhombomeric origin of branchial arch mesenchyme. Later in development, axons throughout the hindbrain expressed CRABP I. The results are considered in terms of the role of retinoic acid in the specification of neuronal phenotype in the hindbrain and in axon outgrowth.

Amino Acid Sequence↗
PubMed1991

Characterization of the major promoter for the plasmid-encoded sucrose genes scrY, scrA, and scrB.

Sucrose genes from a Salmonella thompson plasmid were cloned in Escherichia coli K-12. A physical map and a genetic map of the genes were constructed, revealing strong homology with the scr regulon from the Salmonella typhimurium plasmid pUR400. Two promoters were examined after being subcloned into transcriptional fusion vectors. Primer extension analysis and site-directed mutagenesis were used to identify the precise location of the promoter of scrY, scrA, and scrB. Transcription from this promoter was regulated over a 1,000-fold range by the combined effects of ScrR-mediated repression and catabolite repression. A putative cyclic AMP receptor protein binding site centered 72.5 bp upstream of the start point of transcription of scrY appeared to be essential for full activity of the scrY promoter. Transcription from the putative scrK promoter was far less sensitive to repression by ScrR. In ScrR+ cells, readthrough transcription from the putative scrK promoter into scrY accounted for less than 10% of scrY expression.

Amino Acid Sequence↗
PubMed1990

Genetic polymorphisms of Q region genes from wild-derived mice: implications for Q region evolution.

Both serological and DNA sequence analyses were performed to determine the extent of genetic polymorphism in Q region genes. A panel of Qa-2-specific monoclonal antibodies (mAbs) was tested on 35 wild-derived and inbred mouse strains. Members of this reagent panel recognize multiple and distinct epitopes on the Qa-2-bearing molecule(s). Although quantitative variations in Qa-2 levels were observed, no structural polymorphisms were detected. All strains were either entirely positive or entirely negative with the complete set of reagents. Moreover, cell surface Qa-2 expression was not significantly affected by differences in age or sex of the mouse or cell cycle status. To confirm this apparent lack of genetic polymorphism, the polymerase chain reaction (PCR) technique was used to amplify a portion of the 3' end of the Q region genes, Q4 to Q9, from several independent wild-derived strains of mice. Sequence analysis of the amplified material revealed very little evidence of nucleotide divergence. All strains tested had a Q even DNA sequence identical to that of Q6/Q8 in the B10 strain. Likewise, all tested strains had a Q odd DNA sequence identical to Q7/Q9 in the B10 strain. Two strains showed additional Q even sequences, while all strains tested possessed additional Q odd sequences. The observed lack of polymorphism suggests that the Q genes have evolved in a different manner from H-2K and H-2D. Moreover, duplications of these genes appear to have arisen prior to nucleotide sequence divergence.

Aging↗
PubMed1990

Low-dose lovastatin safely lowers cholesterol after cardiac transplantation.

Hypercholesterolemia occurs in many cardiac transplant patients and may aggravate graft coronary arteriopathy as well as contributing to peripheral vascular disease. Lovastatin, which inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase, in doses of 40-80 mg/day effectively lowers cholesterol in the general cardiac population but has been associated with rhabdomyolysis in cardiac transplant recipients. To determine whether lower doses of lovastatin would be effective and safe for lowering cholesterol after cardiac transplantation, 44 patients with blood cholesterol greater than 200 mg/dl at least 6 months after cardiac transplantation received 10-20 mg lovastatin daily. In addition, lovastatin enzyme inhibitor level was assayed in six patients to determine whether metabolism of the drug was abnormal. Lovastatin decreased total cholesterol by 28% from 282 +/- 54 to 208 +/- 62 mg/dl (p less than 0.005), primarily because of reduction in the low-density lipoprotein fractions, and was well-tolerated without any symptoms or abnormal creatine phosphokinase levels in 43 of 44 patients. One patient developed rhabdomyolysis and reversible renal failure when lovastatin was increased to 40 mg daily. Enzyme inhibitor levels in the six transplant patients were 4.2-7.8 times higher than those measured in normal volunteers. Low-dose lovastatin effectively lowers cholesterol in patients after transplantation, but metabolism is altered, perhaps by cyclosporine. Monitoring of enzyme inhibitor levels may be required to allow safe administration of this drug to cardiac transplant recipients.

Cholesterol↗
PubMed1987

An experimental skin sandwich flap on an independent vascular supply for the study of percutaneous absorption.

Further insights into the composite interactive processes of topically applied agents and percutaneous absorption and metabolism by functional skin in vivo have been hampered by the lack of a model system wherein the blood flow to and from the skin is independent but experimentally accessible. Utilizing microsurgical techniques, split-thickness skin grafting with syngeneic skin grafts, and the congenitally athymic (nude) rat, a skin sandwich flap system has been generated that has an independent but accessible vasculature and thus fills this void. We describe the methodology that has been developed to create the flap and present experiments that: demonstrate a lack of significant collateral circulation; quantify the microcirculation of the skin sandwich flap, host side, and graft side at various times during and after the flap has been generated, and note that blood flow to the flap is basically unchanged from host skin; demonstrate the utility of the system in measuring the amount of [14C]benzoic acid that appears in the flap when deposited on the surface in volatile and nonvolatile vehicles as a function of time; and demonstrate the fact that the flap can be reused, and that the total amount of [14C]benzoic acid absorbed across skin does not change in a substantial way as the flap ages.

Animals↗
PubMed1976

Role of donor immunocompetent cells in allograft rejection.

Allotransplantable lines of the BALB/c (H-2d) Leydig cell tumor C4092 were established in DBA/1 (H-2q) mice after maintenance in organ culture. These modified tumors had reduced immunogenicity but were recognized and rejected by previously sensitized DBA/1 mice. The addition of 3.4 X 10(3)-1 X 10(5) peritoneal exudate cells (PEC) from untreated BALB/c mice to cell suspensions of the modified tumor did not restore Immunogenicity when the cell mixture was Inoculated sc Into DBA/1 recipients. However, when equivalent numbers of PEC or spleen cells were inoculated iv into animals receiving the tumor cell suspension sc, the acceptance of the tumors was significantly reduced or prevented. This indicated that the BALB/c lymphoid cells inoculated iv stimulated the immune system of the host, which in turn recognized the tumor cell inoculum. The lack of effect of the BALB/c lymphoid cells when admixed with the tumor did not support the assumption that the loss of passenger lymphoid cells was responsible for the allotransplantability of grafts after organ culture explantation. Additional evidence was presented that supports our view that the reduced immunogenicity was associated with a phenotypic modification of the tumor cells per se.

Animals↗