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Biomedical subjects

E Baker

Publications and source records attributed to E Baker.

At least 109 records · Page 6Linked to original sources
PubMed1995

Pharmacology of a potent long-acting imidazole-5-acrylic acid angiotensin AT1 receptor antagonist.

The angiotensin II antagonistic activity of SB 203220, [E-alpha-[[2-butyl-1-(4-carboxy-1-naphthalenyl)methyl]-1H- imidazol-5-yl]-methylene]-2-thiophene-propanic acid], was examined in several in vitro and in vivo assays. SB 203220 displaced [125I]angiotensin II binding from a variety of tissues including the cloned human AT1 receptor (IC(50)5-15 nM). SB 203220 (10 microM) did not interact with AT2, endothelin (ETA and ETB) or calcitonin gene-related peptide receptors. [3H]SB 203220 bound with high affinity to the AT1 receptor (Kd = 4.9 nM), but dissociated from the receptor at a much slower rate when compared to [3H]SK&F 108566. SB 203220 antagonized intracellular Ca2+ mobilization induced by angiotensin II in rat vascular smooth muscle cells and exhibited a selective and partially insurmountable antagonism of angiotensin II-induced contraction in isolated rabbit aorta. In the aorta, SB 203220 produced a concentration-dependent parallel shift in the concentration-response curve to angiotensin II [EC30 = 5.94 +/- 1.6 10(-11) M] and depressed the maximal contractile response to angiotensin II by approximately 35%. The antagonistic effect of SB 203220 in rabbit aorta was slowly reversible compared to SK&F 108566. SB 203220 displayed no agonist activity and had no effect on the contractile responses to KCl, endothelin-1 or norepinephrine. In rats, SB 203220 at 10 mg/kg i.v. inhibited angiotensin II-induced aldosterone release. Intraduodenal or oral administration of SB 203220 (1-10 mg/kg) to conscious rats and dogs inhibited the pressor responses to exogenous angiotensin II.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1995

Localization of the gene encoding the human heat shock cognate protein, HSP73, to chromosome 11.

The heat shock cognate protein HSP73 (or HSC70) is a member of the HSP70 multigene family. This protein has several functions, including binding to nascent polypeptides to facilitate correct folding and the uncoating of clathrin-coated vesicles. Analysis of somatic cell hybrids by two-dimensional protein gel electrophoresis revealed the presence of a 73-kDa protein in two hybrids containing human chromosomes 5, 6, 9, and 11 in common. Using Western blot analysis, we demonstrate that this protein is a member of the HSP70 family and, by Southern blot analysis, that the HSP73 gene is located on human chromosome 11. Fluorescence in situ hybridization further localized HSP73 to the region 11q23.3-q25. This region is involved in a number of genetic rearrangements and is associated with several well-characterized tumours.

Animals↗
PubMed1995

The brn-2 gene regulates the melanocytic phenotype and tumorigenic potential of human melanoma cells.

The Oct transcription factors N-Oct-3 and N-Oct-5 are differentially expressed in normal melanocytes, melanoma tumors and cell lines. We have cloned the human brn-2 gene and have shown that it encodes both the N-Oct-3 and N-Oct-5 octamer binding activities detected in melanoma cells. The brn-2 genomic locus has been mapped to chromosome 6q16 and although chromosomal aberrations are common in this region in melanoma, no deletion or rearrangement of the brn-2 gene in melanoma cell lines was observed. Sequencing of the entire gene showed that there are no intervening sequences within the open reading frame. Antisense RNA-mediated inhibition of brn-2 gene expression in melanoma cells was associated with a change in morphology and loss of melanocytic and neural crest markers, including the melanocyte transcription factor microphthalmia and the TYRP pigmentation genes. In addition, loss of brn-2 in these cells resulted in the complete loss of ability to form tumors in SCID and nu/nu mice. These results suggest roles for brn-2 in the determination of the melanocytic lineage and in the tumorigenic phenotype of melanoma.

Animals↗
PubMed1995

Association of a chromosome deletion syndrome with a fragile site within the proto-oncogene CBL2.

The fragile site FRA11B has been localized to the p(CCG)n repeat of the CBL2 proto-oncogene. A proportion of Jacobsen (11q-) syndrome patients inherited a chromosome carrying a CBL2 p(CCG)n expansion, which was truncated close to FRA11B. These results have broad implications for the role of p(CCG)n repeat expansion in the aetiology of genetic disease involving chromosome rearrangements.

Base Sequence↗
PubMed1995

Long-term follow-up results of a randomized drug abuse prevention trial in a white middle-class population.

OBJECTIVE: To evaluate the long-term efficacy of a school-based approach to drug abuse prevention. DESIGN: Randomized trial involving 56 public schools that received the prevention program with annual provider training workshops and ongoing consultation, the prevention program with videotaped training and no consultation, or "treatment as usual" (ie, controls). Follow-up data were collected 6 years after baseline using school, telephone, and mailed surveys. PARTICIPANTS: A total of 3597 predominantly white, 12th-grade students who represented 60.41% of the initial seventh-grade sample. INTERVENTION: Consisted of 15 classes in seventh grade, 10 booster sessions in eighth grade, and five booster sessions in ninth grade, and taught general "life skills" and skills for resisting social influences to use drugs. MEASURES: Six tobacco, alcohol, and marijuana use self-report scales were recorded to create nine dichotomous drug use outcome variables and eight polydrug use variables. RESULTS: Significant reductions in both drug and polydrug use were found for the two groups that received the prevention program relative to controls. The strongest effects were produced for individuals who received a reasonably complete version of the intervention--there were up to 44% fewer drug users and 66% fewer polydrug (tobacco, alcohol, and marijuana) users. CONCLUSIONS: Drug abuse prevention programs conducted during junior high school can produce meaningful and durable reductions in tobacco, alcohol, and marijuana use if they (1) teach a combination of social resistance skills and general life skills, (2) are properly implemented, and (3) include at least 2 years of booster sessions.

Adolescent↗
PubMed1995

Gene duplication of the human peptide YY gene (PYY) generated the pancreatic polypeptide gene (PPY) on chromosome 17q21.1.

Neuropeptide Y (NPY), peptide YY (PYY), and pancreatic polypeptide (PP) are structurally related but functionally diverse peptides, encoded by separate genes and expressed in different tissues. Although the human NPY gene has been mapped to chromosome 7, we demonstrate here that the genes for human PYY and PP (PPY) are localized only 10 kb apart from each other on chromosome 17q21.1. The high degree of homology between the members of this gene family, both in primary sequence and exon/intron structure, suggests that the NPY and the PYY genes arose from an initial gene duplication event, with a subsequent tandem duplication of the PYY gene being responsible for duplication of the PYY gene being responsible for the creation of the PPY gene. A second weaker hybridization signal also found on chromosome 17q11 and results obtained by Southern blot analysis suggest that the entire PYY-PPY region has undergone a further duplication event.

Amino Acid Sequence↗
PubMed1995

MRI T staging of squamous cell carcinoma of the oral cavity: radiological-pathological correlation.

Fifty patients with primary or suspected recurrent squamous cell carcinoma of the oral cavity were examined pre-operatively with magnetic resonance imaging (MRI) to determine the tumour stage. Pathological correlation was available in all cases. Twenty-five of 35 patients with primary disease were correctly staged (MR Tstage 0-4). In another four patients there was good size correlation between MR and pathology, but two cases had false positive MR interpretation of bone invasion. MRI has proved accurate at excluding the presence of bone invasion (negative predictive value 97%), but a positive scan may not discriminate between tumour and other dental pathology (positive predictive value 67%). Assessment of local extent was otherwise good with invasion of muscles of the floor of the mouth and muscles of mastication always predicted correctly. Salivary gland abnormality was frequent, and MRI correctly distinguished between obstructive sialectasis and direct invasion. The results of MR staging in patients with recurrent disease were less accurate. Where diagnostic scans can be obtained MRI can provide useful information for the surgeon or radiotherapist regarding the local extent of tumour, and may assist in treatment planning. Assessment of cervical lymphadenopathy can be performed as part of same procedure.

Adult↗
PubMed1995

Cloning of the sulphamidase gene and identification of mutations in Sanfilippo A syndrome.

Sanfilippo A syndrome is one of four recognised Sanfilippo sub-types (A, B, C and D) that result from deficiencies of different enzymes involved in the lysosomal degradation of heparan sulphate; patients suffer from severe neurological disorders. The Sanfilippo syndrome sub-types are also known as mucopolysaccharidosis (MPS) type III (MPS-IIIA, B, C and D), and are part of the large group of lysosomal storage disorders. Each of the MPS-III types is inherited as an autosomal recessive disorder with considerable variation in severity of clinical phenotype. The incidence of Sanfilippo syndrome has been estimated at 1:24,000 in The Netherlands with MPS IIIA (MIM #252900) the most common. MPS-IIIA is the predominant MPS-III in the United Kingdom, and has a similar high incidence to that found in The Netherlands (E. Wraith, personal communication). There is a particularly high incidence of a clinically severe form of MPS-IIIA in the Cayman Islands with a carrier frequency of 0.1 (ref. 4). Due to the mild somatic disease compared to other MPS disorders there is difficulty in diagnosing mild cases of MPS-III, hence Sanfilippo syndrome may be underdiagnosed, especially in patients with mild mental retardation. Here, we report the isolation, sequence and expression of cDNA clones encoding the enzyme sulphamidase (EC 3.10.1.1). In addition, we report the chromosomal localisation of the sulphamidase gene as being 17q25.3. An 11-bp deletion, present in sulphamidase cDNA from two unrelated Sanfilippo A patients, is described.

Amino Acid Sequence↗
PubMed1995

Differential calcitonin gene-related peptide (CGRP) and amylin binding sites in nucleus accumbens and lung: potential models for studying CGRP/amylin receptor subtypes.

Calcitonin gene-related peptide (CGRP), a 37-amino-acid peptide, is a member of a small family of peptides including amylin or islet amyloid polypeptide and salmon calcitonin. These related peptides have been shown to display similar effects on in vitro and in vivo carbohydrate metabolism. The present study was initiated to identify and characterize the binding sites for these peptides in lung and nucleus accumbens membranes prepared from pig and guinea pig. Both tissues in either species displayed high-affinity (2-[125I]iodohistidyl10)humanCGRP alpha ([125I]hCGRP alpha) binding (IC50 = 0.4-7.7 nM), which was displaced by hCGRP8-37 alpha with equally high affinity (IC50 = 0.4-7.3 nM). High-affinity binding for [125I]Bolton-Hunter human amylin ([125I]BH-h-amylin) was also observed in these tissues (IC50 = 0.2-6.0 nM). In membranes from the nucleus accumbens of both species, salmon calcitonin competed for amylin binding sites with high affinity (IC50 = 0.1 nM) but was poor in competing for amylin binding in lung membranes. Rat amylin8-37 competed for [125I]hCGRP alpha binding with higher affinity (IC50 = 5.4 nM) compared with [125I]BH-h-amylin binding (IC50 = 200 nM) in porcine nucleus accumbens, whereas in guinea pig nucleus accumbens, the IC50 values for rat amylin8-37 were 117 and 12 nM against [125I]hCGRP alpha and [125I]BH-h-amylin, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
PubMed1995

Melatonin and cortisol assessment of circadian shifts in astronauts before flight.

Melatonin and cortisol were measured in saliva and urine samples to assess the effectiveness of a 7-day protocol combining bright-light exposure with sleep shifting in eliciting a 12-hr phase-shift delay in eight U.S. Space Shuttle astronauts before launch. Baseline acrophases for 15 control subjects with normal sleep-wake cycles were as follows: cortisol (saliva) at 0700 (0730 in urine); melatonin (saliva) at 0130 (6-hydroxymelatonin sulfate at 0230 in urine). Acrophases of the astronaut group fell within 2.5 hr of these values before the treatment protocols were begun. During the bright-light and sleep-shifting treatments, both absolute melatonin production and melatonin rhythmicity were diminished during the first 3 treatment days; total daily cortisol levels remained constant throughout the treatment. By the fourth to sixth day of the 7-day protocol, seven of the eight crew members showed phase delays in all four measures that fell within 2 hr of the expected 11- to 12-hr shift. Although cortisol and melatonin rhythms each corresponded with the phase shift, the rhythms in these two hormones did not correspond with each other during the transition.

Astronauts↗
PubMed1995

Bovine latent transforming growth factor beta 1-binding protein 2: molecular cloning, identification of tissue isoforms, and immunolocalization to elastin-associated microfibrils.

Monoclonal antibodies to fibrillin 1 (MP340), a component of elastin-associated microfibrils, were used to screen cDNA libraries made from bovine nuchal ligament mRNA. One of the selected clones (cL9; 1.2 kb) hybridized on Northern (RNA) blotting with nuchal ligament mRNA to two abundant mRNAs of 9.0 and 7.5 kb, which were clearly distinct from fibrillin mRNA (10 kb). Further library screening and later reverse transcription PCR by the rapid amplification of cDNA ends (RACE) technique resulted in the isolation of additional overlapping cDNAs corresponding to about 6.7 kb of the mRNA. The encoded protein exhibited sequence similarity of around 80% with a recently identified human protein named latent transforming growth factor beta 1 (TGF-beta 1)-binding protein 2 (LTBP-2), indicating that the new protein was bovine LTBP-2. This was confirmed by the specific localization of bovine LTBP-2 cDNA probes to human chromosome 14q24.3, which is the locus of the human LTBP-2 gene. The domain structure of bovine LTBP-2 is very similar to that of the human LTBP-2, containing 20 examples of 6-cysteine epidermal growth factor-like repeats, 16 of which have the consensus sequence for calcium binding, together with 4 examples of 8-cysteine motifs characteristic of fibrillins and LTBP-1. A 4-cysteine sequence which is unique to bovine LTBP-2 and which has similarity to the 8-cysteine motifs was also present. Antibodies raised to two unique bovine LTBP-2 peptides specifically localized in tissue sections to the elastin-associated microfibrils, indicating that LTBP-2 is closely associated with these structures. Immunoblotting experiments identified putative LTBP-2 isoforms as a 260-kDa species released into the medium by cultured elastic tissue cells and as larger 290- and 310-kDa species in tissue extracts. A major proportion of tissue-derived LTBP-2 required treatment with 6 M guanidine for solubilization, indicating that the protein was strongly bound to the microfibrils. Most of the guanidine-solubilized LTBP-2 appeared to be monomeric, indicating that it was not involved in disulfide-bonded aggregation either with itself or with latent TGF-beta. Additional LTBP-2 was resistant to solubilization with 6 M guanidine but was readily extracted with a reductive saline solution. This treatment is relatively specific for solubilization of microfibrillar constituents including fibrillin 1 and microfibril-associated glycoprotein. Therefore, it can be inferred that some LTBP-2 is bound covalently to the microfibrils by reducible disulfide linkages. The evidence suggests that LTBP-2 has a direct role in elastic fiber structure and assembly which may be independent of its growth factor-binding properties. Thus, LTBP-2 appears to share functional characteristics with both LTBP-1 and fibrillins.

Adaptor Proteins, Signal Transducing↗
PubMed1995

The human OTF1 locus which overlaps the CD3Z gene is located at 1q22-->q23.

The human OTF1 locus encoding the Oct-1 protein has previously been mapped to chromosome 1 cen-->q32 by analysis of somatic cell hybrids. We report here the regional localization of OTF1 to 1q22-->q23 by fluorescence in situ hybridization. The physical linkage of the CD3Z gene to the OTF1 transcription unit also refines the location of the CD3Z locus to 1q22-->q23.

Chromosome Mapping↗
PubMed1995

Assignment of the human skeletal muscle alpha-tropomyosin gene (TPM1) to band 15q22 by fluorescence in situ hybridization.

A sequence-tagged site (STS) was developed for the human skeletal muscle alpha-tropomyosin gene (TPM1) and used to isolate a genomic clone, lambda TPM1.1, containing part of the TPM1 gene. Fluorescence in situ hybridization of this clone to metaphase chromosome spreads localised TPM1 to chromosome band 15q22. This localisation in humans is consistent with that recently described for the mouse.

Animals↗