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Biomedical subjects

G Brown

Publications and source records attributed to G Brown.

At least 397 records · Page 22Linked to original sources

Apolipoprotein B detected in the plasma of a patient with homozygous hypobetalipoproteinaemia: implications for aetiology.

A hypobetalipoproteinaemic kindred is described in which the proband manifested the clinical and biochemical features of the homozygous state. Unlike the apparent complete absence of apolipoprotein B in the plasma of the five cases of homozygous hypobetalipoproteinaemia reported so far, we were able to demonstrate minute quantities of this protein (approximately 0.025% of normal) in the plasma of the proband. This finding suggests that the disorder may not result from a structural gene defect but may rather reflect a failure of secretion.

Apolipoproteins↗

An immunohistochemical method for the localization of N-acetylserotonin (NAS) in the central nervous system. Description, validation, and application of the technique.

Antisera to N-acetylserotonin (NAS) were raised in rabbits by coupling NAS to bovine serum albumin (BSA) through a p-carboxybenzyl (PCB) bridge at the indole N. The specificity and applicability of these antisera in immunohistochemistry is reported. The anti-NAS antiserum and a fluorescein-labeled immunoglobulin were employed to investigate the topographic distribution of immunoreactive NAS (INAS) in the hindbrain (mesencephalon, cerebellum, pons, and medulla oblongata). Positive identification of INAS was confirmed in the granular layer of the cerebellum, the tractus spinalis nervi trigemini and the reticular formation. INAS was also identified in Purkinje cells, cerebellar nuclei, nucleus principalis nervi trigemini, nucleus tractus mesencephali, cochlear and vestibular nuclei, the locus coeruleus, and other brain stem regions. The pattern of INAS distribution is independent of serotonin (5-HT) and norepinephrine (NE), although certain loci could contain both INAS and serotonin or INAS and norepinephrine.

Animals↗

Parental influences on children's eating behavior and relative weight.

We investigated the relationship between selected parent behaviors, child mealtime behavior, and infant relative weight. Subjects were 7 male and 7 female children varying in age from 12 to 30 months (mean = 23.9 months). Each subject and parents were observed during the dinnertime meal on two occasions using the BATMAN (Bob and Tom's Method of Assessing Nutrition). The children spent 58% of the mealtime eating. They spent very little time making active decisions about what and how much they ate (food requests = 2% of the time; food refusals = 1% of the time). We found significant correlations between child relative weight and (a) parental prompts to eat (r = .81, p less than .001), (b) parental food offers (r = .51, p less than .05), and (c) parental encouragement to eat (r = .82, p less than .001). Thus, the present study suggests a relationship between certain parental variables and the relative weight of their children.

Body Weight↗

Isolation and characterisation of dimethylsulphoxide resistant variants from the human promyeloid cell line HL60.

The HL60 line can be induced to differentiate into neutrophils by 1.25% dimethylsulphoxide (DMSO) or monocytes by 12-O-tetradecanoylphorbol-13-acetate (TPA). Seven variants of this line have been isolated which do not respond to 1.25% DMSO. Five of these lines can be induced to mature into neutrophils using DMSO concentrations of 1.75% (HL60 m2, m4, Sp1 and Ast3) and 2.0% (HL60 Ast25). Two lines, HL60 Ast1 and 4, showed minimal differentiation even at a concentration of 2.0% DMSO, and 2.25% DMSO was toxic to these cells. Of the seven variant lines, HL60 Ast3, Ast4 and Sp1 failed to differentiate into monocytes in response to TPA. Sublines from HL60 that either require higher concentrations of DMSO to induce maturation or fail to differentiate into neutrophils, such as those described above, can be used to investigate how genetically determined properties within HL60 cells affect the ability to mature into neutrophils.

Antigens, Surface↗

Fibronectin levels in normal subjects and patients admitted to a respiratory intensive care unit.

The mean serum fibronectin level of normal subjects, measured by radio-immunoassay, was 363 micrograms/ml (+/- 72 micrograms/ml; 1 SD). The levels were lower in younger subjects and in females using oral contraceptives. In most patients admitted to a respiratory intensive care unit fibronectin levels were low initially, and only remained low in those cases in which severe complications developed. There were no rapid fluctuations of fibronectin levels measured on a daily basis, suggesting therefore that a consumptive reduction of fibronectin is not a feature. The fibronectin molecule itself has abnormal properties in pathological cases and is poorly precipitable by heparin. These studies do not support the proposal that administration of plasma or cryoprecipitates would be beneficial chiefly because of the fibronectin content.

Adolescent↗

The location of redox centers in biological membranes determined by resonance x-ray diffraction. I. Observation of the resonance effect.

We have developed resonance X-ray diffraction methods to locate for the first time intrinsic metal atoms associated with redox centers within biological membrane systems. The study of membranes containing dilute concentrations of resonant scatterers has been made possible by the development of synchrotron radiation sources of X-rays. The technique permits altering the scattering power of a particular atom relative to others by varying the incident X-ray energy. Thus, this method may be used to locate a metal atom within a complex integral protein without chemical modification of the membrane. We present resonance diffraction data taken with synchroton radiation for two different membrane systems: cytochrome oxidase incorporated into lipid vesicles and a photosynthetic reaction center-cytochrome c complex also reincorporated into lipid vesicles.

Cell Membrane↗

The location of redox centers in biological membranes determined by resonance x-ray diffraction. II. Analysis of the resonance diffraction data.

In the preceding paper (Stamatoff, J., Eisenberger, P., Blasie, J.K., Pachence, J.M., Tavormina, A., Erecinska, M., Dutton P.L. and Brown, G. (1982) Biochim. Biophys. Acta 679, 177-187), we described the observation of resonance X-ray scattering effects from intrinsic metal atoms associated with redox centers in membrane proteins on the lamellar X-ray diffraction from oriented multilayers of reconstituted membranes. In this paper, we discuss the possible methods of analysis of such data and present the results of our model refinement analysis concerning (a) the location of the cytochrome c heme iron atom in the profile structure of a reconstituted membrane containing a photosynthetic reaction center-cytochrome c complex and (b) the location of the heme a and a3 iron atoms in the profile structure of a reconstituted membrane containing cytochrome oxidase. The former results are of special importance because they provide a test of the validity of the resonance diffraction data and the methods of analysis, since the location of cytochrome c in the reaction center-cytochrome c membrane profile is known independently of the resonance diffraction experiments.

Animals↗

The specific inhibition of cellular clonogenic proliferation using 211At labelled lectins and antibodies--I.

A monoclonal antibody with a broad anti-human leucocyte specificity, designated BK 19.45 and the plant lectin Concanavalin A have been labelled with the alpha-emitting cyclotron produced radiohalogen astatine-211. Both human and murine tumour cell lines and human leukemic bone marrow samples have been specifically labelled with these radioactive proteins. In all cases the amount of 211At bound to the cells is directly correlated with a decrease in cellular reproductive potential as shown by the ability of the cells to proliferate in a clonogenic assay. For the labelled monoclonal antibody experiments, the radiation dose needed to yield 37% cell survival, the D37 dose, may be achieved with an average of 12 211At atoms/cell.

Animals↗

Variant cell lines from the human promyelocyte line HL60.

The continuous human promyeloid cell line HL60 may be induced to differentiate into neutrophils by the presence of 1.25% dimethylsulphoxide (DMSO) and related compounds [4]. When treated with 12-O-tetradecanoylphorbol-13-acetate (TPA), the cells exhibit may features characteristic of monocytes/macrophages [13]. In both cases, the induced HL60 cells lose their proliferative ability. The availability of this inducible cell line has led to an increasing number of studies aimed at dissecting the process of myeloid differentiation. However, the correct interpretation of such studies may only be reached through the use of appropriate cellular controls; specifically, variant HL60 cell lines which do not differentiate in response to the inducing agents. Here we report the isolation and characterization of two variant cell lines of HL60 which do not differentiate in the presence of 1.25% dimethylsulphoxide but still respond to TPA. Comparison of these HL60 variants with the parental line should facilitate the elucidation of molecular events which regulate myeloid differentiation.

Cell Division↗

Effects of parenteral keyhole limpet hemocyanin or cholera toxin on intestinal immune response to keyhole limpet hemocyanin.

This study evaluated whether subcutaneous priming with either keyhole limpet hemocyanin (KLH), a protein antigen lacking toxic properties, or cholera toxin (CT), whose toxic activity is known to modulate immune responses, would enhance or suppress the local intestinal IgA response to KLH. In rabbits given KLH into chronically isolated ileal loops, subcutaneous priming and boosting with the same antigen resulted in increased serum and loop fluid IgG anti-KLH, but loop fluid IgA anti-KLH was not statistically significantly different from controls. With subcutaneous administration of CT, loop fluid IgA anti-KLH and serum IgG anti-KLH showed a suggestion of an earlier rise than in controls, but were not significantly different. The failure of subcutaneous KLH or CT to enhance local intestinal IgA immune response to KLH indicated that the feasibility of parenteral priming must be determined individually for each antigen to which intestinal immunity is desired.

Animals↗

Aberrations in lymphocyte subpopulations and function during psychological stress.

Eight trainees in psychiatry taking their final oral fellowship examinations were compared with 16 controls to determine the effect of stress on their immune system. Two measures of stress were utilized to distinguish the highly stressed subjects from those minimally stressed. T cell subpopulations, B cell numbers, mitogen reactivity, natural killer cell activity, plaque forming cell responsiveness, antigen specific T suppressor cell activity, and hormone levels were studied 2 weeks before and 2 weeks after the exam. The results demonstrated transiently elevated numbers of T and B lymphocytes but impaired plaque forming cell and mitogen responsiveness in the highly stressed group prior to their exam which normalized later. The results support the concept that stress may significantly alter the immune response in man.

Adult↗

Studies of human myeloid antigens using monoclonal antibodies and variant lines from the promyeloid cell line HL60.

Monoclonal antibodies were produced using mice immunized with the human promyeloid cell line HL60. Two antibodies are described which identify antigens selectively expressed by myeloid cells. Studies using normal bone marrow and myeloid leukaemia cells demonstrated that one of these antibodies (AGF4.48) identifies an antigen expressed throughout the promyeloid to neutrophil stages of maturation. In contrast, the second antibody (AGF4.36) identifies an antigen expressed at the promyeloid to metamyeloid stages and is absent from most blood neutrophils. The HL60 line can be induced to differentiate into neutrophils by 1 . 25% dimethylsulphoxide (DMSO) (Collins et al., 1978). Variant lines from HL60, unresponsive to 1 . 25% DMSO, lack the 'transient' myeloid antigen (AGF4.36) and show a reduced expression of the myeloid antigen (AGF4.48). The variant lines can be induced to mature using higher DMSO concentrations (1 . 5-1 . 75%) and do not express the 'transient' antigen (AGF4.36) during their maturation. The use of these lines in studies of myelopoiesis is discussed.

Animals↗

A prospective study of children with head injuries: II. Cognitive sequelae.

A 2 1/4-year prospective study of children suffering head injury is described. Three groups of children were studied: (a) 31 children with 'severe' head injuries resulting in a post-traumatic amnesia (PTA) of at least 7 days; (b) an individually matched control group of 28 children with hospital treated orthopaedic injuries; and (c) 29 children with 'mild' head injuries resulting in a PTA exceeding 1 hour but less than 1 week. Individual psychological testing was carried out as soon as the child recovered from PTA, and then again 4 months, 1 year, and 2 1/4 years after the injury. A shortened version of the Wechsler Intelligence Scale for Children (WISC), the Neale Analysis of Reading Ability and a battery of tests of specific cognitive functions were employed. The mild head injury group had a mean level of cognitive functioning below the control group, but the lack of any recovery; during the follow-up period indicated that the intellectual impairment was not a consequence of the injury. In the severe head injury group, the presence of cognitive recovery and a 'dose-response' relationship with the degree of brain injury showed that the intellectual deficits were caused by brain damage. Some degree of cognitive impairment was common following head injuries giving rise to a PTA of at least 2 weeks. Conversely no cognitive sequelae, transient or persistent, could be detected when the PTA was less than 24 hours. The results were less consistent in the 1-day to 2-week PTA range, but the evidence suggested that a broadly defined threshold for impairment operated at about that level of severity of injury. Timed measures of visuo-spatial and visuo-motor skills tended to show more impairment than verbal skills but otherwise there was no suggestion of a specific pattern of cognitive deficit. Recovery was most rapid in the early months after injury, but substantial recovery continued for 1 year with some improvement continuing n the second year in some children, especially those with the most severe injuries. Age, sex and social class showed no significant effects on the course of recovery.

Achievement↗

A prospective study of children with head injuries: III. Psychiatric sequelae.

A 2 1/4-year prospective study of children suffering head injury is described. Three groups of children were studied: (a) 31 children with 'severe' head injuries resulting in a post-traumatic amnesia (PTA) of at least 7 days; (b) an individually matched control group of 28 children with hospital-treated orthopaedic injuries; and (c) 29 children with 'mild' head injuries resulting in a PTA exceeding 1 hour but less than 1 week. A retrospective assessment of the children's pre-accident behaviour was obtained by parental interview and teacher questionnaire immediately after the accident and before the behavioural sequelae of the injury could be known. Further psychiatric assessments were undertaken 4 months, 1 year and 2 1/4 years after the initial injury. The mild head injury group showed a raised level of behavioural disturbance before the accident but no increase thereafter. It was concluded that head injuries resulting in a PTA of less than 1 week did not appreciably increase the psychiatric risk. By contrast, there was a marked increase in psychiatric disorders following severe head injury. The high rate of new disorders in children with severe head injuries who were without disorder before the accident, together with the finding of a dose-response relationship with the severity of brain injury, indicated a causal relationship. However, the development of psychiatric disorders in children with severe head injuries was also influenced by the children's pre-accident behaviour, their intellectual level, and their psychosocial circumstances. With the exception of social disinhibition and a slight tendency for the disorders to show greater persistence over time, the disorders attributable to head injury showed no specific features.

Amnesia↗

No impairment of local intestinal immune response to keyhole limpet haemocyanin in the absence of Peyer's patches.

The role of Peyer's patches in the local intestinal and serum antibody responses to keyhole limpet haemocyanin (KLH) was studied in rabbits with chronically isolated ileal loops. Four weekly doses of 400 microgram KLH were administered into loops prepared with and without Peyer's patches. Isotype-specific IgA and IgG anti-KLH in loop secretions collected twice each week and in sera collected weekly were assessed by enzyme-linked immunosorbent assay. Fluid IgA anti-KLH in loops without Peyer's patches first showed a statistically significant increase on day 25, 1 week later than control loops with Peyer's patches. However, some animals in the group without Peyer's patches showed a rise as early as day 7, and the differences from controls were not statistically significant at any time. No statistically significant rise in fluid or serum IgG anti-KLH occurred in either group. Thus, Peyer's patches were not essential for local intestinal antibody response to KLH, a soluble macromolecular antigen. The findings suggest that the innumerable small lymphoid nodules in the gastrointestinal tract, or other mechanisms of antigen processing, play an important role in local intestinal immune responses.

Animals↗

Evaluation of heroin maintenance in controlled trial.

Ninety-six confirmed heroin addicts requesting a heroin maintenance prescription were randomly allocated to treatment with injectable heroin or oral methadone. Progress was monitored throughout the next 12 months by research workers operating independently of the clinic. Heroin can be seen as maintaining the status quo, with the majority continuing to inject heroin regularly and to supplement their maintenance prescription from other sources; it was associated with a continuing intermediate level of involvement with the drug subculture and criminal activity. Refusal to prescribe heroin while offering oral methadone constituted a more confrontational response and resulted in a higher abstinence rate, but also a greater dependence on illegal sources of drugs for these who continued to inject. Those offered oral methadone tended to polarize toward high or low categories of illegal drug use and involvement with the drug subculture, and were more likely to be arrested during the 12-month follow-up. There was no difference between the two groups in terms of employment, health, or consumption of nonopiate drugs. Refusal to prescribe heroin resulted in a significantly greater drop out from regular treatment.

Adolescent↗

Endometrial carcinoma after Hodgkin disease in childhood.

A 34-year-old patient developed metastic endometrial carcinoma after Hodgkin disease in childhood. She had ovarian failure after abdominal irradiation and chemotherapy for Hodgkin disease, and received exogenous estrogens, a treatment implicated in the development of endometrial cancer in menopausal women. Young women on replacement estrogens for ovarian failure after cancer therapy may also have increased risk of endometrial carcinoma and should be examined periodically.

Adenocarcinoma↗