PubMed HealthSearch

Biomedical subjects

J W Burgess

Publications and source records attributed to J W Burgess.

17 recordsLinked to original sources

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

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

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

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

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

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

cAMP-dependent protein kinase isozymes with preference for histone H2B as substrate in mitochondria of bovine heart.

Mitochondria from bovine hearts were fractionated by three different procedures and the fractions were characterized by marker enzymes. Highly purified outer membranes, membrane vesicles, and inner membranes, as well as two high-speed soluble fractions, were obtained. Azide (or oligomycin) resistant ATPase was not found to be a marker for outer membranes. The data were consistent with the association of the protein kinase activity with the soluble matrix of the mitochondria. Activity was highest with histone H2B as the substrate, with histone H1 next in preference. In contrast to the mitochondrial protein kinases studied previously, protamine, casein, and phosvitin were very poor substrates and there was no detectable phosphorylation of pyruvate dehydrogenase. Activity was stimulated by cAMP but not by cGMP, calmodulin, or phosphatidylserine--diolein, with or without Ca2+. Two cAMP-dependent isozymes were separated from the soluble fraction of the mitochondria by chromatography on DE-52 columns. Phosphorylation of histone H2B by the isozymes was inhibited by 98% by Kemptide.

Animals

There is less thalamic degeneration in neonatal-lesioned than in adult-lesioned cats after cerebral hemispherectomy.

In order to study age-related processes of degeneration and recovery, the left hemitelencephalon was surgically removed in 5 adult cats and 5 neonatal kittens which were compared to 5 intact controls. After long survival, brains were sectioned in the coronal plane and thionine-stained. Drawings of gross and microscopic thalamic structures were made at 4 planes and computer-digitized to provide 7 measures: total thalamic area at planes A 7.5 and A 8.5; counts of neuroglia, small neurons (31-100 microns2) and large neurons (101-1000 microns2); area of neuroglia, small neurons and large neurons. All cellular measurements were in the ventrobasal complex at planes A 8.0 and A 10.0. Morphological changes were found bilaterally in all lesioned cats. Ipsilateral to the ablation in adult-lesioned cats, thalamic area, large neuron count and glia cells size were markedly and significantly decreased (P less than 0.01), while in neonatal-lesioned cats these changes were present but significantly reduced in magnitude compared to adult-lesioned animals. In addition, adult-lesioned cats showed a marked increase in glial cell numbers (P less than 0.01) and a decrease in small neuron size (P less than 0.01), while kitten-lesioned animals did not show changes in these measures. In the intact side of the brain, the thalamus of adult-lesioned cats was decreased in size (P less than 0.01), and glial cells were decreased in number and size (P less than 0.05), while in kitten-lesioned brains there were few changes. In both lesioned groups large neurons showed a significant increase in size (P less than 0.01). We conclude that neonatal hemispherectomy results in markedly less thalamic atrophy, retrograde neuronal degeneration and gliosis than the equivalent lesion in adults. The changes are discussed in the context of the increased neuroanatomical reorganization and functional recovery which were reported in neonatal- vs adult-lesioned animals.

Aging

Recovery of functions after neonatal or adult hemispherectomy in cats. III. Complex functions: open field exploration, social interactions, maze and holeboard performances.

Complex behavioral patterns were studied in cats with removal of the entire left cerebral hemisphere either as neonates (n = 10) or adults (n = 11), and in intact control cats (n = 24). Adult-lesioned cats showed decreased open field activity in locomotion, rearing and sniffing. Lesioned kittens showed similar deficits at 100 days of age, but by 150 days of age they resembled normal littermates in all 3 measures. In the presence of another cat, adult-hemispherectomized cats violated species-typical body-buffer space, approaching and attacking other cats. By comparison, normal cats never attacked and seldom approached in the open field. Neonatal-lesioned adults showed only occasional approach and a tendency to sit or stiff-walk in the presence of other cats; attacks were rare. Adult-lesioned cats responded poorly to reversal training for preferred arm of a T-maze, whereas neonatal-lesioned adults were significantly more trainable. Similarly, adult-lesioned cats exhibited a search deficit in a baited holeboard, while neonatal-lesioned adults searched normally. Overall, these results demonstrate that in this animal model, enhanced recovery following early vs adult lesions can also be found in relatively complex, spontaneous behavioral responses not previously studied in this regard.

Aging

Recovery of function after neonatal or adult hemispherectomy in cats: I. Time course, movement, posture and sensorimotor tests.

Cats with removal of the left hemitelencephalon (hemispherectomy) as neonates (n = 12) or in adulthood (n = 14), were compared using a battery of 16 neurological and behavioral tests given when they were young adults (kittens) or at least 5 months after the lesion (adults). The neonatal-lesioned subjects grew normally and performed markedly and significantly better than adult-lesioned cats in 13 tests covering the wide range of movement, posture and sensory functions which were assessed. None of the animals recovered tactile placing of the right forelimb or a normal vision in the right visual field. However, the overall recovery was outstanding for all cats such that the neonatal-lesioned were hard to differentiate from intact controls in their spontaneous, daily activities. Because the lesions were similar in the two age-at-lesion groups, and since numerous functions were followed for prolonged, comparable postlesion time, we conclude that, after hemispherectomy in the cat, there definitely is greater functional recovery if the lesion is sustained early in life. We propose that the enhanced recovery of function in neonatal-lesioned cats is largely due to the extensive anatomical reorganization which we have demonstrated in ongoing studies, and which contrasts with a lesser remodeling in adult-lesioned cats.

Age Factors

Recovery of function after neonatal or adult hemispherectomy in cats. II. Limb bias and development, paw usage, locomotion and rehabilitative effects of exercise.

To investigate the relationship of age-related processes in the recovery of complex motor functions of the limbs, a variety of neurobehavioral assessments were applied to cats with either neonatal (n = 9) or adult (n = 11) removal of the entire left hemitelencephalon (hemispherectomy). Neonatal-lesioned kittens showed no paw preference in reaching for a manipulandum between 5 and 8 weeks of age; thereafter they developed a preference (5.6%) for the unimpaired left limb which persisted throughout adulthood. Adult-lesioned cats showed a significantly greater left bias (13.9%) than neonatal-lesioned cats and they exhibited more abnormal movements and postures when reaching with the impaired limb. Exercising the impaired limb, was effective in reversing the paw preference bias in all lesioned cats. To master a food retrieval task with the impaired limb, adult-lesioned cats required more trials than the neonatal-lesioned group, extensive food deprivation and at least 1 month of postsurgical recovery. However, after mastering this task all cats could continue to perform it indefinitely in their home cages. In a paw print analysis of locomotion, only adult-lesioned cats showed abnormalities including splayed paws, decreased stride length, and adduction of the right hind limb. The results support the 'Kennard Principle' of enhanced recovery following neonatal vs late brain lesions for the present complex motor patterns and are interpreted in the context of neural plasticity and anatomical reorganization during development.

Adaptation, Physiological

Social spiders.

Explore the source record for details and available documents.

Animals

Pharmacological doses of insulin equalize insulin receptor phosphotyrosine content but not tyrosine kinase activity in plasmalemmal and endosomal membranes.

Following insulin administration to intact rats, the insulin receptor kinase activity of subsequently isolated cell fractions was significantly augmented. Of interest was the observation that the endosomal insulin receptor tyrosine kinase displayed four- to six-fold greater autophosphorylation activity than that of plasma membrane. Surprisingly, the endosomal insulin receptor tyrosine kinase displayed a decrease in beta-subunit phosphotyrosine content compared with that seen in the plasma membrane. These observations prompted the suggestion that insulin receptor tyrosine kinase phosphotyrosine dephosphorylation mediated by an endosome-specific phosphotyrosine phosphatase(s) yields activation of the endosomal insulin receptor tyrosine kinase. In a previous study we examined the effect of subsaturating doses of injected insulin. In this work we evaluated insulin receptor tyrosine kinase activity and phosphotyrosine content in plasma membrane and endosomes after a receptor-saturating pharmacological dose of insulin (150 micrograms/100 g body weight). At this dose the phosphotyrosine content per receptor was reduced compared with that seen earlier at insulin doses of 1.5 and 15 micrograms/100 g body weight. Endosomal insulin receptor tyrosine kinase was greater than that seen at the lower nonsaturating insulin doses. Furthermore, endosomal insulin receptor tyrosine kinase activity exceeded that of the plasma membrane, despite retaining about the same phosphotyrosine content per receptor. These data are consistent with the view that insulin receptor tyrosine kinase activity may be regulated by a particular pattern of phosphotyrosine content on the beta-subunit wherein both activating and inhibitory phosphotyrosine residues play a role.

Amino Acid Sequence