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J Scott

Publications and source records attributed to J Scott.

At least 271 records · Page 15Linked to original sources
PubMed1995

Survival, metastasis and recurrence of oral cancer in relation to pathological features.

The outcome of 123 patients with squamous cell carcinoma of the oral/oropharyngeal mucosa treated by primary radical surgery and simultaneous neck dissection and followed up for a maximum of 5 years is reported and related to the pathological features of the tumour. Actuarial survival analysis showed the overall 1-year survival probability was 84%, falling to 69% at 2 years, and 65% at 5 years. For patients without lymph node metastasis, the corresponding survival probabilities were 95%, 86% and 86%, respectively; and for patients with metastasis, 71%, 52% and 44%, respectively. In all, 30 patients (24%) died of their oral cancer; 16 (13%) of local recurrence, 10 (8%) of regional recurrence and 4 (3%) of systemic metastases. In addition to lymph node metastasis, survival was related to the site and stage of the primary tumour, histological pattern of invasion, status of the resection margins and, for patients with metastasis, the number and anatomical level of positive nodes and the presence and extent of extracapsular spread. These pathological features are important indicators of tumour behaviour and should be incorporated into protocols for assessment of prognosis.

Adolescent↗
PubMed1994

Molecular cloning, expression and chromosomal localisation of human AMP-activated protein kinase.

A cDNA encoding rat liver AMP-activated protein kinase (AMPK) was used to isolate human skeletal muscle AMPK cDNA clones. Human AMPK cDNA is more than 90% homologous to the rat sequence and predicts a protein of molecular mass 62.3 kDa, which closely agrees with the mass observed in Western blots of human tissues. AMPK antibodies were also shown to immunoprecipitate AMPK from human liver extracts. A cDNA probe was used to identify a 9.5kb transcript in several human tissues and to isolate human genomic clones. PCR mapping of rodent/human hybrid cell lines localised the human AMPK gene to chromosome 1, and fluorescent in situ hybridisation with a human genomic clone was used to sub-localise the human AMPK gene to 1p31.

AMP-Activated Protein Kinases↗
PubMed1994

Analysis of the micronuclear B type surface protein gene in Paramecium tetraurelia.

The micronuclear DNA of Paramecium contains sequences that are precisely excised during the formation of the macronuclear (somatic) genome. In this paper we show that four eliminated sequences ranging in size from 28 to 416 base pairs, are present in or near the micronuclear copy of the B surface protein gene. Each excised sequence is bounded by the dinucleotide 5'-TdA-3'. Comparison of the micronuclear B gene with the previously determined micronuclear sequence of the A surface protein gene shows that although the positions of at least three of the eliminated sequences are conserved in both genes, the sequences are highly divergent. Transformation of vegetative macronuclei with fragments of the micronuclear B gene results in replication and maintenance of the DNA, but the micronuclear specific sequences are not removed. Previous studies have shown that the correct incorporation of the B gene into the new macronucleus requires copies of the macronuclear B gene in the old macronucleus. Using macronuclear transformation, we show that the micronuclear B gene can substitute for the macronuclear B gene with regard to its role in DNA processing. This suggests that the macronuclear DNA is not acting as a guide for the excision of the micronuclear specific sequences.

Animals↗
PubMed1994

Adenovirus-mediated gene transfer of rat apolipoprotein B mRNA-editing protein in mice virtually eliminates apolipoprotein B-100 and normal low density lipoprotein production.

Apolipoprotein (apo) B-100 is the major protein component in low density lipoprotein (LDL); it contains the binding domain for the LDL receptor and the attachment site for apolipoprotein(a) in lipoprotein(a). ApoB-48 is colinear with the amino-terminal half of apoB-100 and misses the part of the molecule required for LDL receptor interaction and lipoprotein(a) formation. ApoB-48 mRNA is produced by the editing of apoB-100 mRNA, a process by which the codon CAA for Gln-2153 is changed to UAA, an in-frame stop codon. We used the cloned catalytic component of the rat apoB mRNA-editing enzyme (REPR) to construct a replication-defective recombinant adenoviral vector containing REPR cDNA (AvREPR) and a control vector (Av1LacZ4) containing a beta-galactosidase cDNA to investigate the effect of REPR gene delivery in C57BL/6 mice. Intravenous injection of AvREPR in mice resulted in efficient transduction of liver cells, where REPR mRNA and protein were overexpressed, reaching a peak at 7 and 12 days, returning toward control levels at 39 days after AvREPR administration. ApoB mRNA editing activity in liver extracts showed changes parallel to those of REPR mRNA expression; the proportion of edited apoB mRNA in the total hepatic apoB mRNA increased from approximately 60% to more than 90% at the peak of REPR expression. The proportion of plasma apoB-100 in AvREPR-transduced animals decreased from approximately 50% to < 10% of total plasma apoB concentration. Plasma very low density lipoproteins were polydisperse in control animals with an average diameter of 54.9 +/- 20.6 nm (uninjected control) and 54.7 +/- 16.8 nm (Av1LacZ4-treated), respectively. They became much smaller (average diameter 39.3 +/- 12.7 nm) and more uniform in size at day 12 following AvREPR administration. On the same day, the normal plasma LDL (26.2-25.5 nm) was almost completely eliminated in treated animals. Adenovirus-mediated transfer of the REPR cDNA is an efficient method to reduce plasma apoB-100 and normal LDL production.

APOBEC-1 Deaminase↗
PubMed1994

Characterization and chromosomal localization of the human homologue of a rat AMP-activated protein kinase-encoding gene: a major regulator of lipid metabolism in mammals.

AMP-activated protein kinase (AMPK) phosphorylates and inactivates acetyl-CoA carboxylase and beta-hydroxy beta-methylglutaryl-coenzyme A (HMG-CoA) reductase which are the major enzymes involved in fatty acid and lipid biosyntheses. The AMPK gene from rat (rAMPK) has recently been cloned [Carling et al., J. Biol. Chem. 269 (1994) 11442-11448]. In order to study the structure and function of the human AMPK gene (hAMPK), we have cloned the gene, and report in this communication its nucleotide (nt) sequence, tissue distribution and chromosomal location. Our results show that the ORF of hAMPK encodes 552 amino acids (aa) (62.250 kDa) and is highly conserved with rAMPK with identities of 97.3 and 90% at the aa and nt levels, respectively. The hAMPK gene bears homology to a yeast protein kinase-encoding gene (snf1) that regulates carbohydrate metabolism, and also with three other genes encoding SNF1-like kinases from different plant species, namely Arabidopsis thaliana, Hordeum vulgare and Secale cereale. As determined by fluorescent in situ hybridization of a human metaphase chromosome spread, hAMPK maps to chromosome 1p31. The size of the hAMPK transcript is 8.5 kb and the transcription start point (tsp) is located approx. 46 bp upstream from the ATG codon. While 10-15% of AMPK is alternatively spliced in most tissues of the rat, our RT-PCR analyses of the hAMPK mRNA did not reveal the presence of any alternatively spliced form of the gene in human tissues. An interesting aspect of AMPK is that its expression, unlike in rat liver, could not be detected in human liver, and thus the purported role of the gene in controlling fatty-acid synthesis in the human liver remains to be determined.

AMP-Activated Protein Kinases↗
PubMed1994

Microsomal triglyceride transfer protein, the abetalipoproteinemia gene product, mediates the secretion of apolipoprotein B-containing lipoproteins from heterologous cells.

Apolipoprotein (apo) B is an obligatory component of triglyceride-rich lipoproteins. In the rare autosomal recessive disorder abetalipoproteinemia (ABL), no triglyceride-rich lipoproteins are secreted. Mutations in the gene encoding the 97-kDa subunit of a microsomal triglyceride transfer protein (MTP) cause ABL (Sharp, D., Blinderman, L., Combs, K. A., Klenzle, B., Ricci, B., Wager-Smith, K., Gil, C. M., Turck, C. W., Bouma, M. E., Rader, D. J., Aggerbeck, L. P., Gregg, R. E., Gordon, D. A., and Wetterau, J. R. (1993) Nature 365, 65-69; Shoulders, C. C., Brett, D. J., Bayliss, J. D., Narcisi, T. M., Jarmuz, A., Grantham, T. T., Leoni, P. R. D., Bhattacharya, S., Pease, R. J., Cullen, P. M., Levi, S., Byfield, P. G. H., Purkiss, P., and Scott, J. (1993) Hum. Mol. Genet. 2, 2109-2116). Here we have examined whether MTP is both necessary and sufficient to mediate the secretion of apoB-containing lipoproteins from cells that do not normally express either of these proteins. Carboxyl-terminal truncated forms of apoB, apoB17, and apoB41 on the centile system were expressed in COS-1 cells. ApoB17 was secreted whereas apoB41 was unable to traverse the secretory pathway. Cotransfection of apoB41 and MTP promoted the secretion of apoB41 as a buoyant lipoprotein particle with a modal density of 1.15 g/ml. When cotransfected COS-1 cells were cultured under conditions that increase the secretion of apoB100 from HepG2 cells, secretion of apoB41 was similarly increased. N-Acetyl-leucyl-leucyl-norleucinal (ALLN), a calpain I inhibitor, abolished intracellular degradation of apoB41 and increased secretion 2.5-fold. Oleate, a substrate for triglyceride synthesis, reduced degradation from 50 to 19% and increased secretion by 2.5-fold. The effects of ALLN and oleate were additive. We conclude that the secretion of apoB from COS-1 cells cotransfected with apoB and MTP is determined by the competitive processes of lipoprotein assembly and intracellular degradation in the endoplasmic reticulum and that MTP is the only tissue-specific component, other than apoB, required for the secretion of apoB-containing lipoproteins.

Abetalipoproteinemia↗
PubMed1994

Yeast SNF1 is functionally related to mammalian AMP-activated protein kinase and regulates acetyl-CoA carboxylase in vivo.

The product of the SNF1 gene is a protein kinase whose activity is essential for transcriptional activation of glucose repressed genes in Saccharomyces cerevisiae. We have cloned a mammalian AMP-activated protein kinase (AMPK) that is 46% identical to the deduced amino acid sequence of SNF1 (Carling, D., Aguan, K., Woods, A., Verhoeven, A.J.M., Beri, R., Brennan, C.H., Sidebottom, C., Davison, M.D., and Scott, J. (1994) J. Biol. Chem. 269, 11442-11448). Mammalian AMPK plays a major role in the control of lipid metabolism and phosphorylating, thereby inactivating both acetyl-CoA carboxylase and 3-hydroxy-3-methylglutaryl-CoA reductase, key regulatory enzymes in the synthesis of fatty acids and cholesterol, respectively. We present evidence indicating that, in common with its mammalian homologue, SNF1 forms part of a protein kinase cascade. SNF1 is inactivated in vitro by treatment with protein phosphatase 2A and can be reactivated using a partially purified preparation of mammalian AMPK kinase. SNF1 undergoes a time-dependent increase in activity during growth in glucose-derepressing conditions, providing the first evidence that SNF1 activity is regulated by the level of available glucose. In wild-type yeast, but not in a snf1 deletion mutant, acetyl-CoA carboxylase shows a reciprocal change in activity compared with SNF1 under glucose derepressing conditions, indicating that SNF1 regulates acetyl-CoA carboxylase in vivo. These results suggest that, in addition to their structural similarity, the role of SNF1 and AMPK in the regulation of fatty acid synthesis has been highly conserved throughout evolution.

AMP-Activated Protein Kinases↗
PubMed1994

Black-white differences in serum sex hormones and bone mineral density.

To determine if differences in serum sex hormones contribute to racial differences in bone mass, independent of obesity, the authors compared bone mass and sex steroid hormone levels in 273 white women and 86 black women aged 65 years or older. This study was ancillary to the Study of Osteoporotic Fractures. Black women were recruited at two clinical centers in Baltimore, Maryland, and the Monongahela Valley, near Pittsburgh, Pennsylvania. An age-stratified random sample of white women was chosen from the Pittsburgh clinic. Demographic and historical information and anthropometric measurements were obtained from a clinic questionnaire, interview, and examination. Single photon absorptiometry was obtained at three sites: the distal radius, the proximal radius, and the calcaneus. Serum estrone, androstenedione, and testosterone were measured using extraction, column chromatography, and radioimmunoassay. Serum estrone concentrations were significantly higher and androstenedione levels were significantly lower in black women compared with white women. Racial differences in estrone could be explained largely by differences in the degree of obesity. Bone mass was greater in black women compared with white women within age, body mass index, (kg/m2), and estrone strata. Androgens were not related to bone mass. Within each race, bone mass increased linearly with increasing concentration of serum estrone. There was no interaction between race and serum estrone on bone mass. Each factor contributed independently and significantly to the regression model predicting bone mass. There was no attenuation of the effect of race if estrone was included in the model. In conclusion, race and serum estrone were independent determinants of bone mass.

Aged↗
PubMed1994

A review of dental injuries and the use of mouthguards in contact team sports.

Dental injuries are the commonest type of orofacial injury sustained during participation in sports. Of the types which are currently available, custom-made mouthguards fitted by a dentist have been demonstrated to provide the greatest protection from dental injuries. Such mouthguards should therefore be recommended for use by those who participate in contact sports, and their provision should be actively encouraged by dental care workers.

Athletic Injuries↗
PubMed1994

Mammalian AMP-activated protein kinase is homologous to yeast and plant protein kinases involved in the regulation of carbon metabolism.

In mammals, an AMP-activated protein kinase (AMPK) phosphorylates both acetyl-CoA carboxylase and 3-hydroxy-3-methylglutaryl-CoA reductase in vitro and has been proposed to play a major role in the regulation of lipid metabolism in vivo. We report here the primary sequence of rat AMPK and show that antibodies raised against synthetic peptides based on the deduced sequence of AMPK immunoprecipitate AMPK activity from rat liver extracts. AMPK has a remarkable degree of sequence identity to the proteins encoded by the yeast SNF1 gene and the plant RKIN1 gene. SNF1 protein kinase activity is essential for release of genes from glucose repression in Saccharomyces cerevisiae. Expression of cRKIN1 in yeast snf1 mutants restores SNF1 function. These results indicate that AMPK, SNF1, and RKIN1 form part of a family of protein kinases that have been highly conserved throughout evolution. Our results suggest that AMPK may be involved in the regulation of a wide range of metabolic pathways.

AMP-Activated Protein Kinases↗
PubMed1994

Lifestyle and sociodemographic factors as determinants of blood lead levels in elderly women.

This report presents descriptive data on blood lead levels in 530 white women aged 65-87 years and examines the association of blood lead level in this population with specific variables, including age, diet, reproductive and lifestyle factors, and place of residence. Women were recruited from an urban (Baltimore, n = 205) and a rural site (the Monongahela Valley, Pennsylvania, n = 325) during the period 1990-1991. Information on lifestyle, medical history, and demographics was obtained by questionnaire and interview. Blood lead concentrations were measured by atomic absorption spectrophotometry. The mean blood lead level of this cohort (5.3 micrograms/dl) was nearly 60% lower than that reported by a national survey in 1976-1980 for white women aged 65-74 years (12.8 micrograms/dl). Urban women had significantly higher blood lead levels than rural women (p < 0.0001). Urban residence, smoking, alcohol consumption, and years since menopause were positively associated with blood lead level, while body mass index, breast feeding, current estrogen replacement therapy, moderate physical activity, and calcium intake were inversely associated. These data suggest that mean blood lead levels have declined dramatically since 1980. Because it is not known at what level of lead exposure adverse health effects occur, other factors that modify lead levels, metabolism, or susceptibility, such as nutrition and consumption of tobacco and alcohol, become important.

Age Factors↗
PubMed1994

What factors predict discrepancies between self and observer ratings of depression?

This study used a matched clinician and self-rating scale, the Inventory for Depressive Symptomatology (IDS; Rush et al., 1986), in the assessment of 48 patients meeting DSM-III-R criteria for non-psychotic major depressive disorder. Patients generally rated their symptoms as more severe than the clinician, but differences between the self and clinician rating (the delta-IDS) were significantly correlated with non-endogenous depressive subtype, higher levels of neuroticism and dysfunctional attitudes, and lower self-esteem. Multiple linear regression analysis which controlled for severity of depression demonstrated that whilst neuroticism, dysfunctional attitudes and self-esteem accounted for 48.5% of the variance in delta-IDS, the variable accounting for most of the variance was low self-esteem (47.9%).

Adult↗
PubMed1994

Urethral valve incision using a modified venous valvulotome.

Anterior and posterior urethral valves have been treated with a variety of methods. The gold standard for treatment of posterior urethral valves is direct vision transurethral fulguration with the patient under general anesthesia. We report a bi-institutional experience using an adapted venous valvulotome to incise the obstructing valve leaflets. During the last 4 years 15 patients were treated, 4 with anterior and 11 with posterior urethral valves. There were no complications associated with this technique, and we believe that this is a safe and simple treatment option.

Child↗
PubMed1994

A gene for hereditary haemorrhagic telangiectasia maps to chromosome 9q3.

Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disorder that is characterized by frequent nosebleeds, mucocutaneous telangiectases and vascular malformations that cause recurrent haemorrhage and arteriovenous shunting. Linkage analyses in one kindred identified an HHT locus on the long arm of chromosome 9 (maximum multipoint lod score = 6.20 between D9S60 and D9S61). Analyses in two other unrelated HHT families demonstrated that the disease in one was not linked to the locus on chromosome 9q3. We conclude that HHT is a genetically heterogeneous disorder. Based on its map location (9q3) and expression in vascular tissues, type V collagen is a possible candidate gene for HHT.

Adult↗