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J W Burgess

Publications and source records attributed to J W Burgess.

At least 19 recordsLinked to original sources
PubMed1996

Desialylated LDL uptake in human and mouse macrophages can be mediated by a lectin receptor.

We have compared the uptake of desialylated low density lipoprotein (LDL) with other modified forms of LDL in mouse peritoneal macrophages and PMA-activated human U937 monocytes. Neuraminidase-treated LDL (NT-LDL) caused significant cholesterol ester accumulation in both cell types, although the efficiency relative to loading with acetylated LDL (AcLDL) was markedly different, suggesting a very different complement of receptors in the cells. We therefore determined the effect of PMA-activation on lipoprotein receptor expression in U937 cells and found that while scavenger receptor concentration was elevated after PMA-activation, there was no significant change in the expression of the LDL receptor. Receptor specificity of NT-LDL uptake was examined by competition experiments using the degradation assay. This showed that 125I-labelled NT-LDL uptake in U937 cells could largely be accounted for by the persistent expression of the LDL receptor in these cells. In contrast, in mouse peritoneal macrophages where LDL receptor expression is very low, 125I-labelled NT-LDL degradation was also effectively competed by asialofetuin. Surprisingly, 125I-labelled NT-LDL degradation was also effectively competed by AcLDL. Measurement of sialic acid content of AcLDL showed that approximately 14% of the LDL sialic acid, equivalent to 2 to 3 residues per particle, was lost during acetylation of LDL with acetic anhydride. Thus competition between 125I-labelled NT-LDL and AcLDL could be due to lectin receptor binding rather than competition for scavenger receptor binding.

Animals↗
PubMed1996

A role for tyrosine phosphorylation in both activation and inhibition of the insulin receptor tyrosine kinase in vivo.

Upon insulin binding, a conformational change in the insulin receptor (IR) leads to IR beta-subunit autophosphorylation, an increase in IR beta-subunit exogenous tyrosine kinase activity, and the rapid endocytosis of the ligand-receptor complex into endosomes. Previous work has shown that upon internalization, rat hepatic endosomal IRs manifest increased autophosphorylating and exogenous tyrosine kinase activity compared to IRs located at the plasma membrane. As this period of enhanced activity is associated with reduced endosomal IR beta-subunit phosphotyrosine content, it has been proposed that partial dephosphorylation of the internalized IR beta-subunit by an endosomally located phosphotyrosine phosphatase(s) [PTPase(s)] mediates this effect. To test whether endosomal PTPase activity was required for internalization-dependent augmentation of IR tyrosine kinase activity, the present study used the peroxovanadium PTPase inhibitor, bisperoxo(1,10-phenanthroline)oxovanadate anion [bpV(phen)], to block IR dephosphorylation within this subcellular compartment. Rats were pretreated with bpV(phen) before receiving insulin (1.5 micrograms/100 g BW). bpV(phen) inhibited the dephosphorylation of 32P-labeled hepatic endosomal IR by approximately 97% at 15 min post-bpV(phen) injection and prevented a decrease in IR beta-subunit phosphotyrosine content after IR internalization. Fifteen-minute bpV(phen) pretreatment produced a significant reduction (75%; P < 0.001) in maximal insulin-stimulated endosomal IR exogenous kinase activity and decreased IR autophosphorylating activity by 4.3-fold in this subcellular fraction. In conclusion, these findings suggest that an hepatic endosomal PTPase(s) regulates internalization-dependent increases in IR exogenous tyrosine kinase activity.

Animals↗
PubMed1995

Control of p62 binding to TGN38/41 by phosphorylation.

TGN38/41 cycles between the trans-Golgi network (TGN) and plasma membrane, traversing three sorting compartments: the TGN, plasma membrane and early endosome. The targeting signals responsible for this complex itinerary reside in a short cytoplasmic domain of 33 amino acid residues. We show that phosphorylation of the cytoplasmic domain of TGN38 prevents binding of p62--a cytoplasmic protein essential for exocytic vesicle formation. Thus the cycle of TGN38/41 traffic, and by implication the pathway of exocytosis, could be controlled by phosphorylation of the TGN38 cytoplasmic domain.

Amino Acid Sequence↗
PubMed1995

Selective activation of the rat hepatic endosomal insulin receptor kinase. Role for the endosome in insulin signaling.

Insulin administration activates the insulin receptor kinase (IRK) in both plasma membrane (PM) and endosomes (ENs) raising the possibility of transmembrane signaling occurring in the endosomal compartment. Peroxovanadium compounds activate the IRK by inhibiting IR-associated phosphotyrosine phosphatase(s). Following the administration of the phosphotyrosine phosphatase inhibitor bisperoxo(1,10-phenanthroline)-oxovanadate (V) anion (bpV(phen)) activation of the hepatic IRK in ENs preceded that in PM by 5 min. When colchicine treatment preceded bpV(phen) administration IRK activation in ENs was unaffected but was totally abrogated in PM. Insulin receptor substrate-1 tyrosine phosphorylation followed the kinetics of IRK activation in ENs not PM and a hypoglycemic response similar to that achieved with a pharmacological dose of insulin ensued. These studies demonstrate that ENs constitute a site for IR-mediated signal transduction.

Animals↗
PubMed1995

In vivo insulin mimetic effects of pV compounds: role for tissue targeting in determining potency.

Peroxovanadium (pV) compounds activate the insulin receptor kinase in hepatocytes and inhibit the dephosphorylation of insulin receptors in hepatic endosomes with highly correlated potencies (Posner, B. I., R. Faure, J. W. Burgess, A. P. Bevan, D. Lachance, G. Zhang-Sun, J. B. Ng, D. A. Hall, B. S. Lum, and A. Shaver J. Biol. Chem. 269: 4596-4604, 1994). After intravenous administration, K2[VO(O2)2(picolinato)].2H2O [bpV(pic)], VO(O2) (picolinato) (H2O)2 [mpV(pic)], K[VO(O2)2(picolinato)].3H2O [bpV(phen)], and K[VO(O2)2(4,7-dimethyl-1,10-phenanthroline)].1/2H2O [bpV(Me2phen)] produced 50% of their maximal hypoglycemic effect at doses of 0.04, 0.04, 0.32, and 0.65 mumol/100 g body wt, respectively. In contrast, their potencies as inhibitors of dephosphorylation were bpV(pic) = bpV(phen) > mpV(pic) = bpV(Me2phen). bpV(pic) stimulated [14C]glucose incorporation into rat diaphragm glycogen in vivo, and its effect was dose dependent, synergistic with insulin, and evident in other skeletal muscles. In contrast, bpV(phen) displayed no effect on glycogen synthesis in skeletal muscle. mpV(pic) stimulated and bpV(Me2phen) had no effect on glycogen synthesis in the diaphragm. bpV(pic) augmented rat diaphragm insulin receptor kinase 2.2-fold with a time-integrated response 70% that of insulin. In contrast, the effect of bpV(phen) was delayed and much reduced. Thus, the in vivo potencies of pV compounds reflect differing capacities to act on skeletal muscle. The ancillary ligand within the pV complex may target one tissue in preference to another.

Animals↗
PubMed1994

Peroxovanadium compounds. A new class of potent phosphotyrosine phosphatase inhibitors which are insulin mimetics.

Twelve peroxovanadium (pV) compounds, each containing an oxo ligand, one or two peroxo anions, and an ancillary ligand in the inner coordination sphere of V, were synthesized, crystallized, and characterized by 51V NMR as > 95% pure. These compounds activated the insulin receptor kinase (IRK) of cultured hepatoma cells, stimulated lipogenesis in adipocytes, and inhibited the in situ dephosphorylation of autophosphorylated IRs and epidermal growth factor receptors of rat liver endosomes. The phosphotyrosine phosphatase inhibitory and IRK activating potencies of these compounds were linearly correlated (r = 0.74; p < 0.003), decayed in parallel in solution, and varied considerably with the ancillary ligands within these compounds. In vivo administration activated rat liver IRK in parallel with its tyrosine phosphorylation. Co-administration of insulin plus pV was markedly synergistic in both respects. pV administration significantly decreased circulating insulin and plasma glucose concentrations; the latter to levels seen after a dose of insulin yielding > or = 50% occupancy of IRs in vivo. Two compounds (mpV(pic) and mpV(2,6-pdc)) displayed relative specificity as phosphotyrosine phosphatase inhibitors by inhibiting IR dephosphorylation to a significantly greater degree than epidermal growth factor receptor dephosphorylation. Thus, pV compounds are the most potent phosphotyrosine phosphatase inhibitors described to date. Their capacity to activate IRK appears to derive from their phosphotyrosine phosphatase inhibitory activity. Their hypoglycemic action is due to a direct tissue effect.

Adipocytes↗
PubMed1994

17 alpha-ethinylestradiol increases transcytosis of asialoglycoproteins in rat liver.

We have measured the hepatobiliary transcytosis of asialofetuin (ASF) and low density lipoprotein (LDL) in rats following treatment with 5 mg of 17 alpha-ethinylestradiol/kg of body weight for 3 days. The rate of appearance of both ligands in bile was increased 5-fold in estradiol-treated rats compared with controls. In contrast, no increase was observed in the transcytosis of dimeric IgA. The majority of the ASF recovered from the bile of estradiol-treated rats was undegraded, indicating transcytic delivery rather than lysosomal discharge. No increase in the rate of endocytosis of ASF was observed. When transcytosis of 125I-LDL was measured in the presence of excess ASF the rate decreased by approximately 70%. Moreover, sialidase treatment of LDL in vitro increased the biliary appearance of LDL 2-fold in estradiol-treated rats, suggesting that the effect of estradiol on both ligands was mediated via the asialoglycoprotein receptor. We conclude that 17 alpha-ethinylestradiol increases the transcytosis of ASF and LDL through mechanisms that alter the intracellular trafficking of the asialoglycoprotein receptor.

Animals↗
PubMed1993

The psychotherapy of giving medications: therapeutic techniques for interpersonal interventions.

We believe that the duration and mileu of medication visits can be appropriately and effectively used for ongoing psychotherapy in patients who must come for the prescription and follow-up of psychiatric medications. Many physicians make unplanned therapeutic suggestions as a matter of course; in contrast, when interventions are planned, codified, and examined with respect to patient's needs and physician's personal internal responses, their effectiveness and consistency can be enhanced. Specific interventions such as role modeling mental health, identifying transference reactions, and addressing family systems process are easily and effectively made, without being onerous or threatening to patients with severe mental illness. Overall, our clinical experience suggests that planned psychotherapy can be advantageously combined with pharmacologic treatment to enhance patients' overall response.

Adult↗
PubMed1992

Decrease in beta-subunit phosphotyrosine correlates with internalization and activation of the endosomal insulin receptor kinase.

In a previous study, we showed that the rat hepatic insulin receptor (IR) kinase of endosomes (ENs) was transiently activated to levels exceeding those of plasma membrane (PM) receptors following insulin injection. Phosphatase treatment of EN receptors abolished IR kinase activation implicating beta-subunit autophosphorylation as a mediator of the activation process (Khan, M. N., Baquiran, G., Brule, C., Burgess, J., Foster, B., Bergeron, J. J. M., and Posner, B. I. (1989) J. Biol. Chem. 264, 12931-12940). In the present study, the phosphotyrosine (PY) content of the IR beta-subunit in PM and ENs was estimated by two different methods. In one method, direct in vivo labeling with 32Pi followed by receptor immunoprecipitation was carried out. In the second method, immunoblotting with antibodies against the submembrane domain of the IR beta-subunit, encompassing residue 960 (alpha 960), and with antibodies against PY (alpha PY) was used to determine the content of PY/beta-subunit in PM and ENs following injection of insulin. By both methods, it was found that the PY content of PM IR was significantly greater than that of IR in ENs. With doses of 1.5 micrograms of insulin/100 g body weight (50% receptor occupancy) or 15 micrograms/100 g body weight (receptor saturation), the PY/beta-subunit of PM IR attained a level 2.0 to 2.5-fold of that observed for the IR of ENs. Surprisingly, the IR of ENs incorporated 3 to 5 times more PY/beta-subunit than those of PM consequent to autophosphorylation. Exogenous IR kinase activity (poly(Glu:Tyr)) in PM changed only slightly with insulin dose. In contrast, EN receptors exhibited a dose-dependent increase in kinase activity coincident with the decrease in PY/beta-subunit levels. A comparison of the proportion of receptor and kinase activity immunoprecipitated by alpha PY both before and after autophosphorylation indicated that ENs but not PM contained a small population of lightly phosphorylated but highly activated receptors. Since Thr12-Lys (IR kinase residues 1142-1153) efficiently inhibited IR autophosphorylation of both PM and EN receptors, Tris phosphorylation of beta-subunit regulatory tyrosines was unlikely. These results may be explicable by a dephosphorylation-dependent activation of IR kinase, as seen with the src family of tyrosine kinases.

Amino Acid Sequence↗
PubMed1992

Neurocognitive impairment in dramatic personalities: histrionic, narcissistic, borderline, and antisocial disorders.

Thirty-seven patients with personalities in the dramatic cluster (DSM-III-R histrionic, narcissistic, borderline, and antisocial) and 40 controls matched for age and gender were evaluated on 16 neurocognitive variables. The evaluation screened for deficits in functions of attention, memory, language, abstraction, and behavior planning/sequencing. Analysis of variance revealed significant deficits in neurocognitive performance among patients with dramatic personalities, particularly in subtests requiring multi-step, multi-element associative operations.

Adult↗
PubMed1991

Relationship of depression and cognitive impairment to self-injury in borderline personality disorder, major depression, and schizophrenia.

Self-injury was studied in 64 adults with borderline personality disorder, major depression, or chronic paranoid schizophrenia. Subjects were rated according to acute depression, chronic depression, self-injurious behaviors, and neurocognitive deficits, as measured by cognitive function examination. Borderline patients showed more self-injurious behaviors and more chronic depressive symptoms than the major depression or schizophrenia groups. Self-injury was not significantly correlated with acute or chronic depression in any group, but self-injury was correlated with neurocognitive deficits in borderline and schizophrenic groups. The results are explained in the context of a neurocognitive model of psychotic thought process in borderline disorder and schizophrenia.

Adaptation, Psychological↗
PubMed1991

The Personality Inventory Scales: a self-rating clinical instrument for diagnosis of personality disorder.

A personality inventory was developed as an aid in securing history and beliefs relevant to the assessment of personality structure and the diagnosis of personality disorders. The inventory was developed by restating DSM diagnostic criteria in everyday language, rewording the resulting statements in the form of True/False questions, and placing these questions in a short, self-paced booklet which subjects could complete in about 15 minutes. The following assessments were made and discussed: construct validity, split-half reliability, test-retest reliability, comparison with a standardized interview, and comparison with actual clinical assessments. The personality inventory is discussed as a useful accompaniment to the diagnostic interview in clinical settings and for research into personality structure and personality disorders.

Adolescent↗
PubMed1989

The development of social group formation in normal and mentally retarded persons from early childhood through old age: neuropsychiatric, developmental, and cognitive implications.

To test the hypothesis that mentally retarded persons exhibit identifiable styles of social grouping, the size and sex composition of spontaneous social groups were studied in 570 mentally retarded and 3,030 nonretarded persons from preschool-elderly ages. Both populations showed similar developmental trends: group sizes increased through childhood, decreased thereafter until middle age, and increased again in the elderly. However, mentally retarded persons formed smaller groups at all ages: solitary individuals predominated with few groups larger than dyads. A subgroup of lower-functioning retarded persons formed even smaller groups. Nonretarded females were more aggregative than males, but mentally retarded persons showed no such sex differences.

Adolescent↗
PubMed1989

Effects of preschool environments on nonverbal social behavior: toddlers' interpersonal distances to teachers and classmates change with environmental density, classroom design, and parent-child interactions.

Toddlers' interpersonal spacing patterns were studied in environments of different density and design. Results showed that an apparently spacious (74 m2) classroom may produce behavioral changes reminiscent of crowding in young children. When more space (864 m2) was available: (1) children increased interpersonal distances overall; (2) children aggregated more with classmates and teachers, fragmenting into subgroups which were separated from the class overall. With visual dividers added to the classroom to facilitate subgrouping, toddlers formed larger subgroups with teachers. Parent/child behavior during separation also affected distances: longer hand-holding and verbalization were found in children who stayed further from others.

Child, Preschool↗