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Biomedical subjects

J C Meyer

Publications and source records attributed to J C Meyer.

At least 19 recordsLinked to original sources
PubMed1992

Rotavirus VP6 modified for expression on the plasma membrane forms arrays and exhibits enhanced immunogenicity.

The major inner capsid protein of rotavirus is VP6, a 42-kDa polypeptide that forms the icosahedral surface of the rotavirus single-shelled particle. A chimeric form of VP6 (VP6sc) was constructed containing an upstream leader sequence derived from the influenza virus hemagglutinin and a downstream membrane-spanning (anchor) domain from a mouse immunoglobulin gene. When VP6sc was expressed in cells using a recombinant vaccinia virus, the protein was transported, glycosylated, and anchored in the plasma membrane as a trimer with the major domains of the protein orientated externally. Immunofluorescence and immunolabeling with colloidal gold indicated that VP6sc also localized in patches on the cell surface; electron microscopy revealed that the protein assembled into two-dimensional arrays which exhibited the same periodicity as the paracrystalline arrays formed by purified (viral) VP6. Mice inoculated with a recombinant vaccinia virus that expressed VP6sc produced rotavirus-specific antibodies at a titer 10 times higher than that achieved when wild-type, intracellular VP6 was delivered in the same way. Presentation at the cell surface therefore may represent a general method for enhancing the immunogenicity of rotavirus proteins.

Animals↗
PubMed1992

Transient expression and mutational analysis of the rotavirus intracellular receptor: the C-terminal methionine residue is essential for ligand binding.

Maturation of rotavirus involves an intracellular membrane budding event in which the single-shelled icosahedral particle interacts with a virus-encoded receptor glycoprotein, NS28, that is located in the rough endoplasmic reticulum membrane. The receptor is a tetramer and is oriented with the C-terminal 131 amino acids on the cytoplasmic side of the membrane (A.R. Bellamy and G.W. Both, Adv. Virus Res. 38:1-48, 1990). We have used the T7-vaccinia virus transient expression system to deliver mutant variants of the NS28 gene to CV1 cells in order to assess the effects of site-specific modifications on receptor function. Three types of mutant proteins have been constructed by altering the extreme C-terminal methionine, cysteine residues within the third hydrophobic domain, and internal residues located within the cytoplasmic portion of the receptor, respectively. Deletion or conservative substitution of the C-terminal methionine completely abolishes receptor activity. Substitution of cysteine residues has no effect on receptor activity or on the ability of the receptor to adopt its native oligomeric state. Internal deletions result only in a reduction in the level of binding. An N-terminally truncated form of the receptor, containing only the cytoplasmic domain, retains full receptor activity and can form membrane-associated tetramers.

Animals↗
PubMed1990

Properties of acid phosphatase in human stratum corneum.

Sheets of stratum corneum were prepared by a trypsinization procedure from human skin samples, homogenized with a freeze press and then fractionated into a soluble fraction and a sediment by centrifugation at 50,000 g. Acid phosphatase (AcP) activity was found in both fractions but the bulk of the activity was detected in the supernatant. Highest activities were observed after treatment with Triton X-100. The bulk of the AcP activity remained bound to the pellet, if suspension and fractionation of the homogenized stratum corneum were performed in acetate buffer in the range between pH 4.0-5.0, probably due to ionic or hydrophobic interactions. AcP activity was totally lost if homogenates or fractions were stored frozen at -20 degrees C in buffers with pH values lower than 4.0. Triton X-100 extracts from whole skin, epidermis, stratum corneum, cultured skin fibroblasts and leukocytes were compared by isoelectric focusing. Extracts from whole skin, epidermis and stratum corneum yielded almost identical patterns with one main AcP activity band at pI of 5.65, whereas a second pronounced band from whole skin behaved similarly to one band from cultured skin fibroblasts and leukocytes (pI 6.1). The prominent band from extracts of stratum corneum and epidermis was not observed in extracts of skin fibroblasts and leukocytes. Hence, we conclude that stratum corneum and epidermis contain a tissue-specific AcP.

Acid Phosphatase↗
PubMed1989

Interaction of rotavirus cores with the nonstructural glycoprotein NS28.

The nonstructural rotavirus receptor glycoprotein NS28 is 175 amino acids long and oriented in the RER membrane with the NH2 terminus on the luminal side and approximately 131 amino acids accessible from the cytoplasmic side. Au et al. (1988) have demonstrated that NS28 is able to interact with rotavirus single-shelled particles (cores) in a receptor:ligand interaction in which NS28 appears to act as the receptor and the rotavirus core as the ligand. This interaction appears to model the events that occur in the infected cell in which virus maturation involves budding of the core into the lumen of the RER. We have investigated the nature of the interaction between cores and NS28 in vitro using membranes derived from SA11 rotavirus-infected MA104 cells and membranes from cells where NS28 and other rotavirus proteins have been expressed using a series of recombinant vaccinia viruses that incorporate appropriate cloned rotavirus genes. The interaction between the core and the receptor is enhanced by the presence of Ca2+ and Mg2+ and Scatchard analysis yields a dissociation constant (Kd) of 5 x 10(-11) M. The major core protein VP6 is the ligand involved because (i) a monoclonal antibody specific for VP6 blocks the reaction, (ii) membranes prepared from cells infected with a double recombinant vaccinia virus which expresses both NS28 and VP6 exhibit a reduced capacity to bind cores, and (iii) VP6 prepared from virus blocks the ability of membranes to bind cores. When VP6, VP7, VP4, and NS28 are expressed singly as the sole viral proteins present in the cell, only membranes from cells expressing NS28 mediate receptor function, indicating that the presence of NS28 is sufficient to mediate the interaction between cores and the membrane and that other viral proteins probably are not involved in the initial receptor:ligand interaction.

Capsid↗
PubMed1989

Factors affecting plasma levels of ketoconazole during long-term treatment.

In the present study we intended to obtain information on the evolution of near-peak blood levels during long-term treatment. 56 patients with an indication for systemic treatment of nail or skin mycoses obtained a daily dose of 200 mg ketoconazole. They were periodically checked for blood level of ketoconazole, clinical and mycological status and enzyme values. The average blood level was 2.8 +/- 1.3 micrograms/ml plasma. The blood level was not influenced by the length of the treatment. A correlation between blood level and weight or sex was not observed, whereas a significant negative correlation occurred between blood level and age (age group 15-30 years: 3.9 +/- 1.3 micrograms/ml; 46-60 years: 2.4 +/- 0.9 micrograms/ml).

Adolescent↗
PubMed1988

[Andrologic studies in patients with X-chromosome recessive ichthyosis].

In the past there have been several reports of testicular abnormalities (hypogonadism, cryptorchidism and so-called atypical germ cells) in patients with recessive X-linked ichthyosis. Anamnestic interviews, clinical as well as chemical investigations in ten patients (aged 25-52 years) with recessive X-linked ichthyosis have been undertaken in order to examine their endocrine and exocrine testicular function. Normal serum levels of gonadotropins were observed in nine of ten patients, while four of ten men had decreased levels of dehydroepiandrosterone. In addition, in eight of these ten patients spermatological alterations were found: two patients suffered from oligozoospermia, while asthenozzospermia occurred in seven patients and teratozoospermia was registered in three men. Although andrological abnormalities were found in five out of ten patients (cryptorchidism, varicocele), the high incidence of spermatological alterations is remarkable. Further investigations will be necessary to clarify whether steroid sulphatase is responsible for some of these alterations, especially for the pronounced asthenozoospermia.

Adult↗
PubMed1987

X-linked recessive ichthyosis. Reinvestigation of a family first described in 1928.

Recent findings in a family with X-linked recessive ichthyosis are presented. The first description of this family in the literature was given and correctly diagnosed by Csörsz in 1928. His paper can be considered one of the most widely cited proofs of the existence of X-linked ichthyosis. The extended pedigree as well as data of steroid sulfatase and arylsulfatase C determinations presented in this paper verify the diagnosis of the X-linked mode of inheritance of ichthyosis in this family. The biochemical investigations carried out on leukocytes of family members resulted not only in a confirmation of the clinico-genetic diagnosis, but they also helped to establish the heterozygous genotype of a female mentioned previously as an affected person.

Aged↗
PubMed1986

[Biochemical diagnosis of X chromosomal ichthyosis].

Steroid sulfatase (STS) and aryl sulfatase C (ASC) in leucocytes, as well as the electrophoretic mobility of the beta-lipoproteins, were analyzed in 34 patients with autosomal dominant ichthyosis (ADI), 18 patients with X-linked recessive ichthyosis (XRI), 7 patients with congenital nonbullous ichthyosis (CNBI), and 48 controls. The geometric means of both STS and ASC were significantly lower in the group of XRI by a factor of approximately 10. Analysis of ASC showed a clear separation of the whole group of XRI patients opposed to patients with ADI and CNBI and the controls, whereas an overlapping was observed for STS. With one exception, the clinical and biochemical diagnosis (sulfatase) was confirmed by the results of the lipoprotein electrophoresis (LPE). This case, clinically and biochemically diagnosed as XRI, exhibited normal electrophoretic mobility of beta-lipoproteins. We conclude: if the electrophoretic mobility of beta-lipoproteins is enhanced, XRI can be diagnosed; if the LPE is normal, XRI cannot be excluded; in this case, the diagnosis of XRI can be confirmed or rejected by analysis of the microsomal sulfatases.

Adult↗
PubMed1985

Plasma concentrations of beta-carotene and canthaxanthin during and after stopping intake of a combined preparation.

During 17 days two groups of 6 and 8 volunteers of the Department of Dermatology ingested 4 and 6 capsules per day of carotenoids (10 mg beta-carotene + 15 mg canthaxanthin per capsule; Phenoro). Heparinized blood was collected twice a week until day 21 and then weekly until day 77. Concentrations of beta-carotene and canthaxanthin in plasma were analyzed by high-performance liquid chromatography during 77 days. Plasma levels of carotenoids were higher in group 2 (6 capsules) than in group 1 (4 capsules) but reached maximum concentrations within the same time. Hence, therapeutic plasma levels of beta-carotene were reached earlier in group 2. According to blood levels, group 2 could be clearly divided in low and high responders. In contrast to canthaxanthin, beta-carotene exhibited a biphasic decline in both groups, with a monophasic asymptotic decrease which was expressed clinically by a pronounced orange to yellow pigmentation of the skin.

Canthaxanthin↗