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Biomedical subjects

M L Scott

Publications and source records attributed to M L Scott.

At least 91 records · Page 5Linked to original sources

Diminished in vitro responsiveness of circulating erythroid progenitor cells to insulin as an indicator of insulin resistance.

While insulin resistance is considered characteristic of extreme obesity, it may be more difficult to demonstrate in less severe forms of obesity. We studied five moderately obese individuals [mean body mass index (MBMI), 34.1 +/- 1.85 (+/- SE) kg/m2], one massively obese patient (BMI, 50.2 kg/m2), and seven age-matched normal subjects (MBMI, 22.4 +/- 0.93 kg/m2). While two of the obese patients had normal glucose tolerance, all had fasting hyperinsulinemia (P less than 0.02 vs. normal subjects) and exaggerated insulin responses after oral glucose challenge, as defined by area under the 3-h insulin response curve (P less than 0.01 vs. normal subjects). That this hyperinsulinemia represented in vivo insulin resistance was supported by the glucose and insulin responses in four individuals to an iv glucose bolus analyzed by the minimal modeling technique. Study of monocyte insulin receptors revealed no reduction in total insulin binding in the four obese patients tested. Since physiological concentrations of insulin stimulate the in vitro growth of normal human erythroid progenitor cells (EPC), we reasoned that this response might be blunted in cells from individuals with endogenous insulin resistance. The mean peak EPC proliferative response (26.7 +/- 9.11% above baseline) in the obese hyperinsulinemic group was significantly less than the corresponding mean value in the control group (92.6 +/- 5.24% above baseline, P less than 0.001). These results suggest that the minimal modeling technique is a sensitive method for the in vivo demonstration of insulin resistance in moderately obese individuals and that EPC responsiveness to physiological concentrations of insulin reflects in vivo insulin sensitivity and may be used as an in vitro indicator of insulin resistance.

Adolescent↗

Effects of cyclic AMP analogues and phosphodiesterase inhibitors on phospholipid biosynthesis in fetal type II pneumocytes.

Purified type II pneumocytes grown in monolayer cultures after isolation from fetal rabbit lung organotypic cultures were employed to investigate effects of cAMP analogues and phosphodiesterase inhibitors on [methyl-14C]choline and [9-10(n)3H]palmitate incorporation into cell lipids. After 24 h exposure to 0.5 mM N6,O2-dibutyryl-cAMP or 8-bromo-cAMP, a significant increase was found in the rate of incorporation of choline into phospholipids. Addition of 1 mM 1-methyl-3-isobutylxanthine or aminophylline also increased incorporation of choline into phospholipids but did not significantly change the incorporation of choline into sphingomyelin. These effects were not due to increased uptake of choline or changes in the pool size of the precursor. Cyclic AMP analogues also stimulated the rate of incorporation of palmitate into most lipid fractions but did not alter the relative percentages of incorporation of either precursor into any of the phospholipids. Phosphodiesterase inhibitors did not significantly change the rate of incorporation of palmitate into neutral lipids and most phospholipids, except for a decrease into sphingomyelin, phosphatidylinositol and phosphatidylethanolamine. However, they increased the percentage of incorporation of palmitate into phosphatidylcholine and decreased the percentage of incorporation into most other phospholipids. These data clearly indicate that cAMP can stimulate the synthesis of phospholipids within the type II pneumocytes. This effect is probably a general stimulation effect for the cAMP analogues but methylxanthines may selectively increase the synthesis of surfactant lipids such as phosphatidylcholine while decreasing that of other membrane-associated phospholipids.

8-Bromo Cyclic Adenosine Monophosphate↗

Nucleotide sequence of the large terminal repeat of two different strains of gibbon ape leukemia virus.

Gibbon ape leukemia virus, SEATO strain (GaLV-SEATO), a virus that induces myeloid leukemia in gibbon apes, and GaLV, San Francisco strain (GaLV-SF), a virus associated etiologically with lymphocytic leukemia in gibbon apes, have been molecularly cloned. The complete nucleotide sequence of the large terminal repeats (LTRs) of both viruses are reported and compared to the previously published nucleotide sequence of the LTR of another member of the same virus group, the simian sarcoma virus (SSV). Substantial homology is evident among all three LTR sequences. The most striking feature of the GaLV-SEATO LTR is the presence of a 45-bp tandem direct repeat in the U3 region, an area likely to contain transcriptional enhancers. Both GaLV-SEATO and GaLV-SF contain a deletion in U3 when compared to SSV. Each of the three LTRs differ from the other two by short deletions in R-U5 and short additions in U3, as well as by numerous point mutations. The possibility that the structural changes observed in the LTR contribute to the differences in the pathogenic effects of these viruses is discussed.

Animals↗

Monoclonal antibodies detect a spectrin-like protein in normal and dystrophic human skeletal muscle.

Spectrin is the major protein of the erythrocyte membrane skeleton, which is bound to the cytoplasmic surface of the membrane's lipid bilayer and is responsible for cell shape and membrane elasticity. Inability to identify spectrin in other cell types led to the assumption that this protein was unique to erythrocytes. However, spectrin-like proteins have been demonstrated recently in a variety of cell types, including skeletal and cardiac muscle, in several species. We used monoclonal antibodies against human erythrocyte spectrin subunits in an immunocytochemical study to detect related proteins in normal and diseased human skeletal muscle. Six of seven monoclonal antibodies against beta-spectrin determinants were bound at the cytoplasmic surface of muscle fiber plasma membranes, whereas none of six monoclonal antibodies against alpha-spectrin determinants was bound. Muscle fibers of patients with neuromuscular diseases showed similar distribution and specificity of antibody binding to those of normal subjects, but the intensity of binding was increased. In contrast, probable regenerating fibers in muscle of patients with muscular dystrophies showed reduced binding of antibodies, but reduced binding was not seen in fetal muscle fibers nor in those of a patient with a myotubular myopathy. We conclude that human skeletal muscle fibers possess a spectrin-related protein associated with their plasma membrane that shows extensive beta-chain similarities to erythrocyte spectrin but differs significantly with respect to the alpha-subunit. Its function may be associated with the maintenance of membrane and myofibril integrity during contraction, and the increased antibody binding in diseased muscle may reflect a structural rearrangement of spectrin or a compensatory increase in spectrin abundance in response to increased stress on these systems.

Antibodies, Monoclonal↗

Insulin receptors in fetal rabbit lung type II cells.

Insulin binding was studied in type II pneumocytes isolated from fetal rabbit lungs (27 days of gestation) and grown in monolayers in tissue culture. The mean high affinity receptor site number was 11.8 +/- 1.4 X 10(3) (+/-SEM)/cell, with a Kd of 0.45 +/- 0.07 nM (n = 6). Low affinity sites averaged 432 +/- 10.7 X 10(3)/cell, with a Kd of 45.6 +/- 11.8 nM. Incubation of the cells with 5 X 10(-10) M (Bu)2cAMP (DBcAMP) and 10(-3) M methylisobutylxanthine (MIX) for 18 h led to significant increases in the number of high affinity receptor sites and Kd (P = 0.025 and 0.05, respectively). Incubation of the cells with insulin (1 microgram/ml) for 18 h led to a significant diminution in the mean number of high affinity sites to 3.23 +/- 0.68 X 10(3)/cell (P = 0.0025). There was no significant change in the Kd of the high affinity sites. There was also no significant change in the number or affinity of the low affinity sites. When the cells were incubated with insulin in the presence of DBcAMP (5 X 10(-4) M) and MIX (10(-3) M), there was a significant increase in high affinity binding sites to a mean of 8.87 +/- 2.18 X 10(3)/cell (n = 4) compared to the value after incubation in the presence of insulin alone. There was no significant increase in the Kd of the high affinity sites. The following conclusions were drawn from these experiments. 1) Fetal type II pneumocytes possess receptors with high affinity for insulin. 2) The up-regulation of insulin receptor binding induced by high ambient concentrations of insulin in vivo in rabbit fetal lungs and circulating human monocytes does not occur in vitro when isolated pneumocytes are grown in tissue culture. 3) Insulin binding to type II pneumocytes is enhanced by DBcAMP and MIX. 4) Insulin down-regulation of receptor binding is significantly counteracted by DBcAMP and MIX.

1-Methyl-3-isobutylxanthine↗

Neuropsychological performance of sexual assaulters and pedophiles.

Persons who had been arrested for sexual assault were administered the Luria-Nebraska Neuropsychological Battery and the results compared to a group of normal controls. The sexual assaulters performed significantly worse on 7 of the 14 scales of the battery. The data were then broken down into three groups: (1) those who had forcibly assaulted postpubescent victims, (2) those subjects who had sexually molested a prepubescent child, and (3) normal controls. A discriminant analysis correctly classified 68% of the subjects on the basis of their neuropsychological performance alone.

Adult↗

Self-monitoring of blood glucose levels and intensified insulin therapy. Acceptability and efficacy in childhood diabetes.

Prospective studies have shown that children and adolescents with diabetes have a high prevalence of serious complications and a sharp reduction in life expectancy. Recently, self-monitoring of blood glucose levels has become available and, for the first time, provides a method for determining the concentration of blood glucose with considerable accuracy. We have introduced this method of control assessment to our pediatric diabetic patient population in conjunction with a program of intensified insulin administration (two or more injections per day). This is a report of the ready acceptance of these methods by children and adolescents and their parents (53/63, or 84%). The effectiveness of this program is evidenced by a progressive and significant reduction in the percentage of glycosylated hemoglobin during a period of 18 months in a majority of the subjects. These observations suggest that improved glycemic control can be achieved in young diabetics by using multiple insulin injections and self-monitoring of blood glucose levels. Whether such control can lead to a better long-term outlook for diabetics remains to be seen.

Adolescent↗

Ventricular enlargement in major depression.

Major depression accompanied by psychosis may be a separate nosological entity from nonpsychotic depression. Investigators have noted behavioral and biochemical differences in psychotic and nonpsychotic patients, as well as differences in response to treatment. A previous study using computed tomography (CT) found enlargement of the lateral cerebral ventricles in patients with manic-depressive illness with psychotic symptoms. The present study examined CT scans of patients with major affective illness that was accompanied by hallucinations, delusions, or both. The ventricles of the depressed group were significantly larger than those of a group of normal controls.

Adult↗

Neuropsychological performance in schizophrenics with histories of substance abuse.

Both schizophrenia and substance abuse have been associated with cerebral impairment, although the neuro psychological performance of schizophrenic patients with substance abuse histories has not been examined. In this study, the Luria-Nebraska Neuropsychological Battery was administered to schizophrenic patients with or without histories of substance abuse. The study found that the schizophrenics without substance abuse histories showed evidence of cerebral dysfunction, while those schizophrenics with histories of substance abuse could not be differentiated from normal.

Adult↗

Comparison of reverse passive antiglobulin haemagglutination with double antibody radioimmunoassay for estimation of total human serum IgE.

Serum IgE levels can be measured by reverse passive antiglobulin haemagglutination (RPAH) using trypsin-treated human red cells coupled to anti-human IgE by chronic chloride. The results are read after only 90 min incubation. RPAH and double antibody radioimmunoassay have been used to measure IgE levels in 100 sera, with levels ranging from 5 to 43,000 international units (i.u.)/ml. Correlation between the two assays was high over the whole range, provided that affinity-purified anti-IgE was used in the RPAH test. When two non-affinity-purified anti-IgE reagents were used in the RPAH, correlation was poor for sera with levels below 1000 i.u./ml. It is concluded that RPAH tests for IgE are of comparable sensitivity and specificity to radioimmunoassay procedures, and provide a useful simple, yet more rapid alternative.

Antibodies, Anti-Idiotypic↗

Molecular cloning and partial characterization of unintegrated linear DNA from gibbon ape leukemia virus.

We have cloned the complete genome of an oncogenic primate retrovirus, the San Francisco isolate of gibbon ape leukemia virus, in a lambda phage vector. DNA sequence analysis and restriction endonuclease mapping of the inserted linear provirus demonstrated 9-base pair inverted repeats at its ends, flanking direct terminal repeats 470 base pairs in length. The (-) strong stop region of this DNA showed surprisingly low sequence homology to that of another gibbon ape leukemia virus isolate from an animal with similar disease. Analysis of the clone also revealed the terminal phosphate configuration of the linear provirus. The recombinant phage is suitable for direct use as a hybridization probe to detect homologous retroviral sequences in human cell lines.

Animals↗