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Biomedical subjects

L Hoyer

Publications and source records attributed to L Hoyer.

9 recordsLinked to original sources
PubMed1998

Sustained phenotypic correction of murine hemophilia A by in vivo gene therapy.

Hemophilia A is caused by a deficiency of blood coagulation factor VIII (FVIII) and has been widely discussed as a candidate for gene therapy. While the natural canine model of hemophilia A has been valuable for the development of FVIII pharmaceutical products, the use of hemophiliac dogs for gene therapy studies has several limitations such as expense and the long canine generation time. The recent creation of two strains of FVIII-deficient mice provides the first small animal model of hemophilia A. Treatment of hemophiliac mice of both genotypes with potent, human FVIII-encoding adenoviral vectors resulted in expression of biologically active human FVIII at levels, which declined, but remained above the human therapeutic range for over 9 months. The duration of expression and FVIII plasma levels achieved were similar in both hemophiliac mouse strains. Treated mice readily survived tail clipping with minimal blood loss, thus showing phenotypic correction of murine hemophilia A by in vivo gene therapy.

Adenoviridae↗
PubMed1998

Molecular mechanisms of virulence in fungus-host interactions for Aspergillus fumigatus and Candida albicans.

Research on fungi that cause opportunistic infections has increased dramatically during the past few years, largely because these organisms cause significant morbidity and mortality. Most of this research has focused on defining the virulence factors produced by these pathogens, as well as developing methods for the diagnosis of fungal diseases. With regard to studies on the biology of Candida albicans, it is now possible to isolate genes, disrupt their expression, and observe the specific effects of gene disruption on virulence and growth of the organism. Moreover, growth and virulence of this pathogen is also being studied and the effect of environmental factors on gene expression investigated. This subject is especially important in view of the fact that C. albicans can colonize and invade a number of sites in the human body. Thus, its ability to grown in the oral and vaginal tracts, as well as in blood, requires the organism to adapt to a variety of environmental stresses. Here we present observations on the growth, morphogenesis and virulence of the opportunistic fungi C. albicans and Aspergillus fumigatus.

Amino Acid Sequence↗
PubMed1996

Moderation of hemophilia A phenotype by the factor V R506Q mutation.

Although many examples of unrelated hemophilia A patients carrying identical point mutations in the factor VIII (FVIII) gene have been reported, the clinical phenotype is not always the same among patients sharing the same molecular defect. Possible explanations for this discrepancy include undetected additional mutations in the FVIII gene or coinheritance of mutations at other genetic loci that modulate FVIII function. We report molecular genetic analysis of potential modifying genes in two sets of unrelated patients carrying common FVIII missense mutations but exhibiting different levels of clinical severity. Both mutations (FVIII R1689C and R2209Q) are associated with severe hemophilia A in some patients and mild/moderate disease in others. The common von Willebrand disease type 2N mutation (R91Q) was excluded as a modifying factor in these groups of patients. However, analysis of the recently described factor V (FV) R506Q mutation (leading to activated protein C resistance) identified a correlation of inheritance of this defect with reduced hemophilia A severity. Two moderately affected hemophilia A patients, each with either of two FVIII gene mutations, were heterozygous for FV R506Q, whereas two severely affected patients and two moderately affected patients were homozygous normal at the FV locus. Our results suggest that coinheritance of the FV R506Q mutation may be an important determinant of clinical phenotype in hemophilia A and that modification of the protein C pathway may offer a new strategy for the treatment of FVIII deficiency.

Alleles↗
PubMed1984

Response of protein C and protein C inhibitor to warfarin therapy in patient with combined deficiency of Factors V and VIII.

The role of Protein C in combined factor V/VIII deficiency was examined by reducing the Protein C concentration using warfarin therapy in a patient with the combined deficiency. The factor VIII deficiency was like Hemophilia-A, with deficiency of VIII:C and VIII:C(Ag), but normal VIIIR:Ag and VIIIR:cof. The factor V deficiency was due to loss of the V antigen. During warfarin therapy the Protein C level was reduced, but concentrations of factors V and VIII did not change. Protein C Inhibitor was normal throughout. Thus combined factor V/VIII deficiency is not related to Protein C levels.

Adult↗
PubMed1978

Visualization of a guinea pig T lymphocyte surface component cross-reactive with immunoglobulin.

Thymus-derived lymphocytes (T cells) show exquisite specificity in recognition of antigens, but the nature of the cell surface receptor is controversial. Although antigen recognition mediated by immunoglobulin variable (V) regions remains the minimal hypothesis, it has been extremely difficult to definitely establish the presence of immunoglobulins on these cells. Chicken antibodies, produced against the (Fab')2fragment of mouse immunoglobulin G (IgG) and purified by binding to and elution from IgG-Sepharose 4B, bind to an endogenously synthesized surface component of guinea pig T cells. The binding occurred via a cross-reaction with murine k chain and a heavy chain determinant localized in the Fd region, and was visualized by immunofluorescence and immunoelectronmicroscopy using both transmission and scanning techniques. These data provide direct evidence for the presence of a surface component related to immunoglobulin on T lymphocytes.

Animals↗
PubMedDate not supplied

Hairy cell leukemia and vasculitis.

A patient with hairy cell leukemia, systemic vasculitis, and HB8 antigenemia is reported. The patient presented with polyarthralgia before the diagnosis of the leukemia and had documented polyarthritis before the subsequent recognition of the vasculitis. The association of systemic vasculitis and hairy cell leukemia in the setting of HB8 antigenemia is discussed. The therapeutic challenge of treating coincident hairy cell leukemia and vasculitis is presented.

Adult↗