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Biomedical subjects

S Beck

Publications and source records attributed to S Beck.

At least 163 records · Page 9Linked to original sources
PubMed1992

A homologue of the Drosophila female sterile homeotic (fsh) gene in the class II region of the human MHC.

The RING3 gene maps in the class II region of the human major histocompatibility complex, at a CpG island distal of the HLA-DNA gene. RING3 cDNAs were obtained from a T cell cDNA library and the longest (4 kb) was sequenced. The sequence contained an open reading frame encoding a protein of 754 amino acids. A screen of protein databases revealed striking homology between the RING3 protein and the Drosophila female sterile homeotic gene (fsh) which is implicated in the establishment of segments in the early embryo. Partial sequence homology was also observed with some other proteins involved in cell cycle control (CCG1), cell division (ftsA) and regulation of cell growth (gamma interferons). This highly conserved gene may play an important role in human development. In addition, its location in the MHC class II region may be related to some HLA-associated diseases.

Amino Acid Sequence↗
PubMed1991

Second proteasome-related gene in the human MHC class II region.

Antgen processing involves the generation of peptides from cytosolic proteins and their transport into the endoplasmic reticulum where they associate with major histocompatibility complex (MHC) class I molecules. Two genes have been identified in the MHC class II region, RING4 and RING11 in humans, which are believed to encode the peptide transport proteins. Attention is now focused on how the transporters are provided with peptides. The proteasome, a large complex of subunits with multiple proteolytic activities, is a candidate for this function. Recently we reported a proteasome-related sequence, RING10, mapping between the transporter genes. Here we describe a second human proteasome-like gene, RING12, immediately centromeric of the RING4 locus. Therefore RING12, 4, 10 and 11 form a tightly linked cluster of interferon-inducible genes within the MHC with an essential role in antigen processing.

Amino Acid Sequence↗
PubMed1991

A proteasome-related gene between the two ABC transporter loci in the class II region of the human MHC.

It is now possible to paint a detailed picture of how cytoplasmic proteins are handled by the immune system. They are apparently degraded in the cytoplasm into peptides. These are then transported into the endoplasmic reticulum where they encounter class I major histocompatibility complex (MHC) molecules. Once loaded with peptide, the HLA molecules move through the Golgi apparatus to the cell membrane. Until recently, it had not been established how peptides without signal sequences cross the ER membrane. However, a number of papers have now described a pair of membrane transporter genes of the ABC (ATP-binding cassette) super-family which are attractive candidates for this function. Both transporter genes, which may encode two halves of a heterodimer, are situated in the class II region of the MHC. There is evidence that other putative components of the processing machinery, the LMPs (low molecular mass polypeptides), are also encoded in the MHC. Similarities between the properties of the LMPs and a large intracellular protease complex, called proteasome, have led to the suggestion that LMPs are involved in processing antigens. We have now identified a human gene with sequence homology to proteasome components. Remarkably, this gene maps between the two putative peptide transporter genes.

Amino Acid Sequence↗
PubMed1991

Trimethoprim-sulfamethoxazole oral desensitization in hemophiliacs infected with human immunodeficiency virus with a history of hypersensitivity reactions.

Hemophiliacs infected with human immunodeficiency virus with a history of hypersensitivity reaction to a combination product of trimethoprim and sulfamethoxazole were desensitized orally. Six of the seven patients included in the study successfully completed the desensitization protocol and received trimethoprim-sulfamethoxazole for 5 to 7 months after desensitization (mean length of treatment, 5.7 months) for prophylaxis of Pneumocystis carinii pneumonia. The small number of patients and the short follow-up allow us to suggest that oral desensitization may be an effective and inexpensive means to treat hemophiliacs infected with human immunodeficiency virus with trimethoprim-sulfamethoxazole as prophylaxis against Pneumocystis carinii pneumonia.

AIDS-Related Opportunistic Infections↗
PubMed1991

Amino acid sequence of mouse tenascin and differential expression of two tenascin isoforms during embryogenesis.

We have isolated cDNA clones for mouse tenascin and analyzed expression of tenascin mRNAs during embryonic development of the kidney and gut. The deduced amino acid sequence of the mouse tenascin cDNAs shows a modular structure of repeats similar to chicken and human tenascin. In mouse there are 14.5 cysteine-rich repeats with similarity to the EGF repeat, followed by several repeats with similarity to the type III repeat of fibronectin. A longer variant contains 13 fibronectin type III repeats, whereas a shorter splice variant of mouse tenascin lacks the 5 type III repeats that occur directly after the fifth repeat in the longer variant. Contrary to the chicken and human sequences, mouse tenascin does not contain an RGD sequence in the third type III repeat implicated in cell attachment, or in any other positions. In Northern hybridizations to RNA from primary embryonic fibroblasts, the cDNA clone M 20/1 detects two mRNAs with sizes close to 6 and 8 kb. This, and the other data presented here suggest that the two major mouse tenascin polypeptides arise through an alternative RNA splicing. The two major mRNAs are differentially expressed during development. The 8-kb mRNA is more prominent than the 6-kb mRNA throughout prenatal kidney development, but during postnatal development the ratio of the two mRNAs changes. A different expression pattern is seen in the developing gut where the 6-kb mRNA predominates during embryogenesis with the 8-kb mRNA appearing later. The mRNA data of the developing gut correspond with previous protein data, which showed that the shorter Mr 210,000 polypeptide predominates during earlier developmental stages and the larger Mr 260,000 polypeptide appears later in the embryonic gut (Aufderheide, E., and P. Ekblom. 1988. J. Cell Biol. 107:2341-2349).

Amino Acid Sequence↗
PubMed1991

The DNA sequence of the human cytomegalovirus genome.

In the first part of this article we review what has been learnt from the analysis of the sequence of HCMV. A summary of this information is presented in the form of an updated map of the viral genome. HCMV is representative of a major lineage of herpesviruses distinct from previously sequenced members of this viral family and demonstrates striking differences in genetic content and organization. The virus encodes approximately 200 genes, including nine gene families, a large number of glycoprotein genes, and homologues of the human HLA class I and G protein-coupled receptor genes. The HCMV sequence thus provides a sound basis for future molecular studies of this highly complex eukaryotic virus. The second part discusses the practical rate of DNA sequencing as deduced from this and other studies. The 229 kilobase pair DNA genome of human cytomegalovirus (HCMV) strain AD169 is the largest contiguous sequence determined to date, and as such provides a realistic benchmark for assessing the practical rate of DNA sequencing as opposed to theoretical calculations which are usually much greater. The sequence was determined manually and we assess the impact of new developments in DNA sequencing.

Base Sequence↗
PubMed1991

An HCMV reading frame which has similarity with both the V and C regions of the TCR gamma chain.

Human cytomegalovirus (HCMV) is a member of the herpes virus family and is characterized by widespread infection, latency, persistence and reactivation and is a serious pathogen particularly of immunosuppressed patients. Previously HCMV was shown to encode a glycoprotein homologous to the MHC class I antigens. We report here that HCMV may encode another glycoprotein similar to another sub-group of the Ig superfamily. This putative glycoprotein gene shows similarity to both the constant and variable regions of the human T cell receptor gamma chain (TCR gamma). The level of homology is low but may be of interest as the predicted gene might have some role in virus infection or immune evasion.

Amino Acid Sequence↗
PubMed1991

Vigabatrin in pediatric epilepsy--an open study.

The antiepileptic effect of vigabatrin in adults has been demonstrated in a number of controlled studies. In children, the effect of vigabatrin has been investigated only to a limited extent. In order to assess the long-term effect and safety of vigabatrin in patients with severe epilepsy, an open, add-on, dose-ranging study was initiated. To date, 27 children with partial epilepsy, two with generalized epilepsy, two with Lennox-Gastaut syndrome, and one with nonclassifiable epilepsy have been enrolled in the trial. Fifty-four percent of patients have experienced a greater than 50% reduction in seizure frequency, and four patients have become seizure free. A significant reduction in seizures was noted across the patient population, although patients who were recorded as seizure free at 3 and 6 months did suffer some recurrence of seizures. However, when seizures recurred, they did so at much lower frequency than recorded at the start of the study. Thirteen patients (39%) reported adverse events attributable to vigabatrin; one was immediately withdrawn from the study, and six had their vigabatrin dose reduced. No physiologic effects were noted on normal growth or clinical physical examination.

Adolescent↗
PubMed1990

Applications of dioxetane chemiluminescent probes to molecular biology.

DNA probes and synthetic oligonucleotides in general present one of the key tools in modern molecular biology research and increasingly also in commercial applications. Along with the many applications that have been developed for and with DNA probes, faster and more sensitive detection methods are being developed. One of the most promising recent developments presents a method based on enzymatically triggered chemiluminescence. Details of this chemistry along with applications in molecular biology and immunology will be discussed and compared to conventional methods.

Chemistry Techniques, Analytical↗
PubMed1990

A complex between the MHC class I homologue encoded by human cytomegalovirus and beta 2 microglobulin.

Human cytomegalovirus (HCMV) is a ubiquitous pathogen that persists in the host and can cause severe disease in the immunocompromised individual or in the fetus. Analysis of the nucleotide sequence of the virus genome has revealed the presence of an open reading frame whose predicted translation product has homology with the heavy chain of the major histocompatibility complex (MHC) class I molecule of higher eukaryotes, and the observed sequence homology was given additional significance by the independent observation that HCMV virions can bind beta 2 microglobulin (beta 2m), the light chain of the MHC class I molecule. We expressed both the HCMV class I homologue and the human beta 2m gene in recombinant vaccinia viruses. We show that the coexpressed gene products associate, that the transport of beta 2m to the cell surface is dependent on coexpression of the class I homologue and that the viral gene product is therefore functionally related to its cellular counterpart. We observe also that, in HCMV-infected cells, no synthesis of mature cellular class I molecules occurs, while messenger RNA levels remain unaltered, and we speculate that one function of the viral homologue may be to sequester beta 2m, thus preventing the maturation of cellular class I molecules and rendering the infected cell unrecognizable by cytotoxic T cells.

Cell Line↗
PubMed1990

[Results of the Leiden mass screening for cervix uteri carcinoma; the 'young' (24-34 years) versus the 'old' (35-54 years) group of women].

The population screening for cervical carcinoma in the Leiden region took place in the period 1977-1988. It involved four screenings of women in the age group 35-54 years, and two screenings of women in the age group 25-34 years, with a screening interval of 3 years. We conclude that screening for cervical carcinoma is useful. Cytological investigation of young women (under 35 years) is indicated. This conclusion is based in part on the data of the regional and national cancer registries and on the mortality figures in The Netherlands. Data on HPV infection in Dutch males and females were also taken into account.

Adult↗
PubMed1990

Mild pantothenate deficiency in rats elevates serum triglyceride and free fatty acid levels.

Pantothenate-derived coenzymes are extensively involved in intermediary metabolism, particularly in the metabolism of lipids. Using a rat model of diet-induced pantothenate deficiency, we hoped in this study to relate pantothenate status, as indicated by serum pantothenate and hepatic coenzyme A, to levels of circulating triglycerides and free fatty acids. Although commercial "vitamin-free" casein contained approximately 3 mg total pantothenate per kilogram, marked changes in serum pantothenate and hepatic CoA still occurred during weeks when rats were fed purified diets supplemented with 0 to 1600 mg pantothenate per kilogram of diet. Conditions in different experiments included ad libitum or pair-feeding of 3- or 6-wk-old rats and blood sampling from 3 to 24 h after feeding. Under most conditions of mild pantothenate deficiency in which weight differences between groups were not statistically significant, serum triglyceride and free fatty acid levels were significantly elevated in pantothenate-deficient groups. Mild pantothenate deficiency appears to have observable in vivo effects on triglyceride metabolism before severe deficiency causes significant weight loss.

Animals↗