Search PubMed⌕ Search

Biomedical subjects

J Scott

Publications and source records attributed to J Scott.

At least 469 records · Page 26Linked to original sources
PubMed1988

Genetic evidence from two families that the apolipoprotein B gene is not involved in abetalipoproteinemia.

Abetalipoproteinemia (ABL) is a recessive disorder in which affected individuals have extremely low or undetectable levels of serum apo B-containing lipoproteins. Using restriction fragment length polymorphisms, we have studied two families, each with two children with classical ABL born of normal parents. In each of these families, the two affected children have inherited different apo B alleles from at least one parent, whereas the siblings would be anticipated to share common alleles if this disorder were due to an apo B gene mutation. This linkage study shows that in these families, the apo B gene is discordant with ABL and therefore the disorder is caused by a defect in another gene, which is important for the normal synthesis or secretion of apo B-containing lipoproteins from both the liver and intestine.

Abetalipoproteinemia↗
PubMed1988

The Newcastle Chronic Depression Study. Patient characteristics and factors associated with chronicity.

Chronic depression is defined as "symptomatic non-recovery for a period of 2 or more years". Chronic primary major depressives (n = 24) were compared retrospectively with a control group of primary major depressives (n = 20) who had recovered from their illness episode within 2 years. The former had a significantly higher familial loading for affective disorder and showed an increased incidence of independent undesirable life events during the 6 months prior to and 2 years after the onset of their illness. Female chronic depressives also had a significantly greater number of previous illness episodes and a more frequent history of thyroid dysfunction. Personality as measured on the EPO, psychiatric problems arising as secondary complications of the depressive illness, and developmental object loss did not differentiate chronic from non-chronic depressives.

Adult↗
PubMed1988

Chronic depression.

Defining chronic depression as persistent symptoms for 2 or more years, a prevalence of chronic depression of 12-15% is found in the literature. A four-part classification of chronic depression is proposed: Chronic Primary Major Depression; Chronic Secondary Major Depression; Characterological or Chronic Minor Depression (Dysthymic Disorder); and 'Double Depression'. The literature indicates several factors predicting chronicity in primary major depression: more at risk are female patients, particularly those with premorbid neurotic personality traits, individuals with unipolar disorders, and those with higher familial loading for such disorders. Other factors are the adequacy and appropriateness of the treatment given, and the length of illness episode prior to treatment being received. Larger studies with well-matched controls are needed.

Adult↗
PubMed1988

Combined modality therapy for advanced Hodgkin's disease: 15-year follow-up data.

From 1969 through 1982, 184 patients with advanced Hodgkin's disease (HD) were treated with combined modality therapy (CMT) at Yale University. The data were reanalyzed in November 1986, with a mean follow-up of 10 years. The patient population consisted of 102 newly diagnosed stages IIIB and IV patients, and 82 patients who had relapsed after initial radical radiotherapy. From 1969 through 1978, the treatment program was induction chemotherapy with nitrogen mustard, vincristine, vinblastine, procarbazine, and prednisone (MVVPP) for three cycles (6 months) followed by low-dose radiation (1,500 to 2,500 cGy) for patients who had achieved complete remission (CR), to all disease sites present before the onset of chemotherapy. From 1978 to 1982, selected "poor-risk" advanced-stage patients received nitrogen mustard, vincristine, procarbazine, prednisone plus Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), bleomycin, vinblastine, and dacarbazine (MOPP-ABVD) induction chemotherapy, while the remaining patients were randomized between MVVPP and MOPP. One hundred fifty-one patients have achieved CR (82%); 23 (15%) of these 151 have relapsed, with the remaining 128 patients in continuous CR. A total of 62 patients have died, 45 due to HD, and 17 due to other causes. Twelve of these 17 patients died of second malignancies. The 15-year actuarial survival of all patients is 54%. It is 71% if deaths due only to HD are considered. Within the overall group of advanced HD patients, age and multiple extranodal sites of involvement continue to constitute adverse risk factors. The three drug programs used were all equivalent. No improvement resulted from the use of MOPP-ABVD in the poor-risk patients. These results compare favorably with those recently published by the National Cancer Institute (NCI). CMT resulted in an approximate 20% improvement in survival with no increase in second malignancies when compared with chemotherapy alone.

Adult↗
PubMed1988

Regional specificities of monoclonal anti-human apolipoprotein B antibodies.

The usefulness of monoclonal antibodies as probes of protein structure is directly related to knowledge of the structures and locations of the epitopes with which they interact. In this report we provide a detailed map of 13 epitopes on apoB-100 defined by our anti-apoB monoclonal antibodies based on current information on the amino acid sequence of apoB-100. To localize antibody specificities to smaller regions along the linear sequence of the apoB-100 molecule we used a) thrombin- and kallikrein-generated fragments of apoB-100; b) beta-galactosidase- apoB fusion proteins; c) heparin; and d) antibody versus antibody competition experiments. Most of the monoclonal antibodies elicited by immunization with LDL were directed towards epitopes within the first 1279 amino terminal (T4/K2 fragments) or last 1292 carboxyl terminal amino acid residues (T2/K4 fragments) of apoB-100. One epitope localized to the mid-portion of apoB-100 was elicited by immunization with VLDL (D7.2). Saturating amounts of heparin bound to LDL did not inhibit the binding of any of the monoclonal antibodies to their respective epitopes on apoB-100, indicating that none of the antibody determinants is situated close to any of the reported heparin binding sites on LDL apoB. We examined the expression of apoB epitopes on VLDL subfractions and LDL isolated from a normolipidemic donor. The apparent affinities with which the antibodies interacted with their respective epitopes on the VLDL subfractions and LDL uniformly increased as follows: LDL greater than VLDL3 greater than VLDL2 greater than VLDL1, suggesting that each of the major regions of apoB-100 is progressively more exposed as normal VLDL particles become smaller in size and epitopes are most exposed in LDL. Previous experiments utilizing hypertriglyceridemic VLDL subfractions yielded similar results, but the rank order of VLDL subfractions and LDL was not the same for all antibodies tested. Thus, differences in apoB epitope expression on VLDL particles of differing sizes is a general phenomenon, but the expression of apoB epitopes in hypertriglyceridemic VLDL appears to be more heterogeneous than is the case for VLDL from normolipidemic donors.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies, Monoclonal↗
PubMed1988

DNA polymorphisms of the apolipoprotein AII and AI-CIII-AIV genes: a study in men selected for differences in high-density-lipoprotein cholesterol concentration.

We have investigated the frequencies of RFLPs of the apolipoprotein (apo) AII gene and of the apo AI-CIII-AIV gene cluster in 109 men, selected from a random sample of 1,910 men aged 45-59 years, to cover a wide range of plasma high-density-lipoprotein (HDL)-cholesterol concentration. There was no significant difference in apo AI or apo AII RFLP allele frequency between groups of individuals with high and low HDL-cholesterol concentration. However, the apo AI PstI RFLP showed an association with genetic variation determining the plasma concentration of apo AI in this sample. Genetic variation in the apo AI-CIII-AIV gene region, as defined by haplotypes, accounted for 16% of the phenotypic variance in the apo AI concentration and for 8% of the phenotypic variance in HDL-cholesterol concentration. There was no significant association between alleles of the apo AII MspI RFLP and genetic variation determining apo AII or HDL concentration. The data demonstrate that genetic variation in the apo AI-CIII-AIV gene cluster is involved in determining the serum concentration of apo AI in this sample of clinically well individuals.

Alleles↗
PubMed1988

Apolipoprotein B: a novel mechanism for deriving two proteins from one gene.

Evidence from antibody and peptide mapping, protein sequencing and amino acid composition studies suggests that intestinal apo-B48 is colinear with the amino terminal half of hepatic apo-B100. To investigate the mechanism of apo-B48 production we examined cDNA clones from human and rabbit small intestine. All clones contained a single C----T base difference from the hepatic sequence resulting in a translational stop at codon 2153. Amplification by the polymerase chain reaction of cDNA from human and rabbit small intestine, rabbit liver and the human hepatoma cell line HepG2 showed that the stop codon was only present in intestinal mRNA. Enterocyte genomic DNA did not contain the stop codon. We suggest that a co- or post-transcriptional C----U change may result in the production of apo-B48, which represents the amino terminal 2152 amino acids of apo-B100. This is the first example of tissue specific modification of a single mRNA nucleotide resulting in two different proteins from the same primary transcript.

Animals↗
PubMed1988

Salivary flow rate, protein and electrolyte concentrations in chronic alcoholic patients.

Stimulated and unstimulated parotid salivas were examined in a series of non-cirrhotic patients under treatment for alcohol dependence and in age-sex matched, non-alcoholic, healthy, control subjects. Resting salivary flow was raised threefold in the alcohol group and the protein and electrolyte concentrations were also altered in this saliva. However, there were no intergroup differences in parotid flow or composition following gustatory stimulation by 6% citric acid. The results contrast with the wide parotid functional changes known to occur in stimulated parotid saliva in alcoholic cirrhosis and suggest, therefore, that the direct salivary effects of chronic alcohol abuse may be less important than the damaged liver function in contributing to the salivary disturbance reportedly occurring in alcoholic cirrhosis.

Adult↗
PubMed1987

A novel form of tissue-specific RNA processing produces apolipoprotein-B48 in intestine.

Evidence suggests that intestinal apo-B48 is colinear with the amino-terminal half of hepatic apo-B100. To investigate the mechanism of apo-B48 production, we examined cDNA clones from human and rabbit small intestine. All clones contained a single C----T base difference from the hepatic sequence, resulting in a translational stop at codon 2153. Amplification by the polymerase chain reaction of cDNA from human and rabbit small intestine, rabbit liver, and the human hepatoma cell line HepG2 showed that the stop codon was only present in intestinal mRNA. Enterocyte genomic DNA did not contain the stop codon. We suggest that a co- or posttranscriptional C----U change may result in the production of apo-B48, which represents the amino-terminal 2152 amino acids of apo-B100. This is the first example of tissue-specific modification of a single mRNA nucleotide resulting in two different proteins from the same primary transcript.

Amino Acid Sequence↗
PubMed1987

Expression of multiple growth factors in a human lung cancer cell line.

U-1810, a human large-cell lung cancer line, was found to express a PDGF-like growth factor. 35S-cysteine labelling and immunoprecipitation revealed the synthesis and secretion of a 31-kDa PDGF-like protein. Serum-free conditioned medium contained PDGF-receptor-competing and mitogenic activity when tested on human fibroblasts. Whereas the receptor-competing activity was fully neutralized by anti-PDGF antibodies, the mitogenic activity was only partially affected. We therefore probed U-1810 mRNA with a panel of growth-factor DNA clones. We found expression of the genes for PDGF A- and B-chains, TGF-alpha, TGF-beta and IGF-II but not EGF or IGF-I. U-1810 cells lacked specific binding sites for PDGF but showed specific binding of EGF and expressed EGF-receptor transcripts. Thus, U-1810 is an example of a human tumor cell line that expresses multiple growth factor genes; in the intact tumor the corresponding growth factors may operate in autocrine stimulation of the tumor cells as well as in paracrine growth reactions (i.e. stroma recruitment).

Cell Line↗
PubMed1987

Bone marrow irradiation chimeras in the BB rat: evidence suggesting two defects leading to diabetes and lymphopoenia.

A series of bone marrow irradiation chimeras were constructed in an attempt to determine the site of the defect(s) leading to diabetes and/or lymphopoenia in the BB rat. In BB rats that were lethally irradiated and reconstituted with T-cell-depleted Wistar-Furth (WF) rat bone marrow, the incidence of diabetes was reduced, and in animals treated with WF bone marrow at less than 44 days of age, the disease was completely prevented. Such animals demonstrated normal lymphocyte counts in peripheral blood, and normal lymphocyte function (as indicated by mixed lymphocyte response), but retained an abnormal T-cell subset distribution only partially improved above that of diabetes-prone BB rats. The incidence of diabetes in these irradiated chimeras was significantly reduced compared to the incidence in BB rats irradiated at the same age but reconstituted with bone marrow from BB rats. In WF rats that were lethally irradiated and reconstituted with T-cell-depleted bone marrow from overtly diabetic BB rats, no diabetes was induced. Such animals demonstrated normal lymphocyte counts in peripheral blood, normal lymphocyte function, and normal T-cell subset distributions. Overall, these results suggest two defects leading to diabetes and/or lymphopoenia in the BB rat. One of these occurs at the level of the bone marrow stem cell while the other resides in the T-cell differentiative environment.

Animals↗