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Biomedical subjects

G Brown

Publications and source records attributed to G Brown.

At least 325 records · Page 18Linked to original sources

The effect of dietary fatty acids on the gastric production of prostaglandins and aspirin-induced injury.

We have investigated in man the effect of dietary supplementation with evening primrose oil (linoleic acid 72%, gamma-linolenic acid 9%) on gastric immunoreactive PGE2 release and aspirin-induced mucosal injury. Twenty healthy volunteers received in a randomized crossover evening primrose oil (2 g b.d.) and olive oil (control) for 2 weeks each. During the last 48 hours of each period, five doses of aspirin 900 mg were taken. In gastric washings on day 7, evening primrose oil had enhanced immunoreactive PGE2 release from a mean of 38 ng/30 min (olive oil) to 80 ng/30 min (P less than 0.05). This, however, was not able to protect against aspirin-induced gastric blood loss which rose from a mean (95% confidence limits) of 1.3 (0.7-2.1) microliters 10 min-1 (evening primrose oil day 7) to 9.4 (5.4-16.5) microliters 10 min-1 (day 14). Although not effective against aspirin, similar dietary supplementation might assist in preventing peptic ulcer recurrence.

Adult↗

The development of cell lineages: a sequential model.

The concept of cell lineage and the empirical characterization of specific lineages provide valuable insight into the problems of developmental biology. Of central interest is the decision-making process that results in the diversification of cell lines. Studies of the haemopoietic system, in which stem cells can be committed to one of at least six pathways of differentiation, have suggested that the restriction of differentiation potentials is a progressive and stochastic process. We have recently proposed an alternative model which hypothesizes that lineage potentials during haemopoiesis are expressed individually and in a predetermined sequence as progenitor cells mature. The model first arises from experimental studies which show that both normal myeloid progenitor cells and a human promyeloid cell line, which are able to differentiate towards either neutrophils or monocytes, express these potentials sequentially in culture. The close linear relationship between other haemopoietic progenitor cells is inferred from collective data from studies of bipotent progenitor cells and of haemopoietic proliferative disorders. If the development of haemopoietic cell lineages shows a tendency to follow a particular program, such a mechanism is likely to operate throughout development. In this paper we consider the evidence in favour of programmed events within progenitor cells implementing diversification, and the implications of predetermined and restricted pathways of embryonic development.

Animals↗

Expression of epithelial membrane and 3-fucosyl-N-acetyllactosamine antigens in cervix uteri with particular reference to adenocarcinoma in situ.

The staining patterns obtained with antiepithelial membrane antigen (anti-EMA) and the monoclonal antibody to 3-fucosyl-N-acetyllactosamine (AGF 4:48) in the uterine cervix in intraepithelial and invasive neoplasia were compared to determine a possible role in differential diagnosis of reactive and neoplastic conditions. Both early invasive and in situ adenocarcinoma stained equally intensely with both agents and both antibodies stained diffusely tubal metaplasia, endometrial lined glands, and even occasional areas of normal endocervical mucosa. It is concluded that these agents are unlikely to be of use in the routine histological differentiation of glandular and squamous cervical dysplasia or neoplasia, but immunostaining with anti-EMA may help differentiate between reactive and metaplastic changes in endocervical glands and adenocarcinoma in situ.

Adenocarcinoma↗

Characterization of a novel nuclear envelope protein restricted to certain cell types.

The monoclonal antibody AGF2.3 identifies a nuclear envelope protein that is restricted to certain cell types. In particular, this antigen shows a reduced level of expression during haemopoietic cell maturation. In this study, we have examined the relationship of this protein to known nuclear envelope proteins that have a similar molecular mass. Antigen extraction and immunoelectron microscope studies revealed that the AGF2.3 protein is an integral membrane protein present at both the inner and outer aspects of the nuclear envelope. The protein is not associated with nuclear pores and therefore is distinct from pore complex proteins. The AGF2.3 protein does not have ATPase activity. Therefore, this protein is also distinct from a myosin heavy chain-like ATPase that is associated with the nuclear envelope. The AGF2.3 antibody identifies a novel nuclear envelope protein. Further studies of the biochemical nature of the AGF2.3 protein should provide insight into novel cellular processes at the nuclear envelope relating to the lineage or maturation status of cells.

Antibodies, Monoclonal↗

Changes in insulin receptor expression in HL60 cells induced to differentiate towards neutrophils or monocytes.

HL60 is a human promyeloid cell line capable of differentiating towards monocytes or granulocytes when treated with appropriate agents. Changes in insulin receptor number, affinity and mRNA levels were observed when HL60 cells were induced to differentiate with 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or dimethylsulphoxide (DMSO). Total and high-affinity insulin receptor numbers decreased following treatment of HL60 cells with DMSO, whereas total insulin receptor number increased and high-affinity receptor number decreased in cells treated with TPA. Three distinct insulin receptor mRNA species of 9.1, 6.3 and 2.8 kb were identified in HL60 cells. The larger 9.1 and 6.3 kb species were increased in both TPA- and DMSO-treated HL60 cells, and the 2.8 kb mRNA was reduced in differentiated cells. Thus HL60 cells differentiated towards monocytes or granulocytes showed similar changes in the levels of individual insulin receptor mRNAs, but displayed contrasting alterations in low-affinity insulin binding. Three HL60 variant lines, which have different capacities to respond to inducers of monocyte and neutrophil differentiation, showed similar levels of total insulin receptors, but differed in their expression of high-affinity receptors. The data provide evidence for the existence of two distinct insulin receptors.

Blotting, Northern↗

Changes in phosphoproteins during commitment of HL60 cells to monocyte differentiation: evidence for multiple protein kinase involvement.

The human promyeloid cell line HL60 differentiates toward monocytes when treated with TPA. We have analyzed, by two-dimensional gel electrophoresis, the phosphoprotein patterns within HL60 cells, labeled to equilibrium with [32P]orthophosphate when cells were treated with suboptimal (1 nM), optimal (5 and 10 nM), and supraoptimal (40 and 100 nM) concentrations of 12-O-tetradecanylphorbol-13-acetate (TPA) as regards the induction of differentiation. No change was detected in the phosphoprotein pattern at 1 nM TPA, whereas four phosphoproteins showed increased levels of phosphorylation at 5 and 10 nM TPA. When cells were treated with 40 and 100 nM TPA, in total eight and ten proteins, respectively, were phosphorylated, including the above four proteins. Two proteins were dephosphorylated when cells were treated with 40 and 100 nM TPA. A 15-kd protein, phosphorylated when HL60 cells were treated with 5 nM TPA, was observed as an intense spot in autoradiographs of total cellular phosphoproteins of two variant HL60 cell lines that are unable to differentiate toward monocytes and prior to treatment with TPA. In the case of three variant cell lines, which like HL60 differentiate toward monocytes, the phosphoprotein spot was almost absent. Thus, paradoxically, the 15-kd phosphoprotein is affected by TPA although its constitutive level of expression or increased phosphorylation state is inversely related to the potential for monocyte differentiation. This observation, together with the TPA dose-response effects on protein phosphorylation, is discussed in relation to multiple protein kinase involvement.

Cell Differentiation↗

Epithelial wound healing enhanced by transforming growth factor-alpha and vaccinia growth factor.

Epidermal regeneration following middermal injuries to skin requires both proliferation and migration of keratinocytes. Epidermal growth factor (EGF) stimulates the proliferation of keratinocytes in culture, and topical administration of EGF accelerates epidermal regeneration of partial thickness burns or split-thickness incisions in vivo. Transforming growth factor-alpha (TGF-alpha) and vaccinia growth factor (VGF) have substantial sequence homology with EGF, and all appear to bind to the same receptor protein. Whether TGF-alpha or VGF can affect epidermal wound healing in vivo is not known. The present studies show that topical administration of TGF-alpha or VGF in antibiotic cream to partial thickness burns (second degree) accelerated epidermal regeneration in comparison with untreated or vehicle-treated burns. Low levels of both TGF-alpha and VGF (0.1 microgram per milliliter) appeared to be more effective than EGF in stimulating epidermal regeneration. Regenerated epithelium from burns treated with TGF-alpha or VGF appeared normal histologically. This finding suggests that topical application of selected growth factors may be useful in accelerating healing of partial thickness injuries.

Animals↗

Reliability of DSM-III diagnoses for major depression and generalized anxiety disorder using the structured clinical interview for DSM-III.

This study examined the interrater reliability of generalized anxiety disorder (GAD) and major depressive disorder (MDD) diagnoses derived from the Structured Clinical Interview for DSM-III (SCID). Using videotaped interviews, paired raters made independent diagnoses of 75 psychiatric outpatients. The percent agreement of the raters was 82% for MDD and 86% for GAD; the respective kappa values were .72 and .79. The results indicated that the SCID can be employed reliably to differentiate MDD from GAD. The SCID is recommended for further research with these disorders.

Adult↗

Self-reported depressive symptoms that differentiate recurrent-episode major depression from dysthymic disorders.

The Beck Depression Inventory (BDI) was administered to 168 outpatients diagnosed with recurrent-episode, major-depression disorders and 99 outpatients diagnosed with dysthymic disorders. The mean ratings of 18 BDI items, except for Sense of Failure, Punishment, and Crying, were comparable in both groups; the mean total-BDI score and mean number of BDI items rated were higher for the major depressive disorders than for the dysthymic disorders. A backward stepwise-discriminant analysis revealed that Suicidal Ideas and Loss of Appetite were the two symptoms that most meaningfully distinguished between the two groups. The major depressive patients described more suicidal ideation and loss of appetite than did the dysthymic patients. The results supported the contention that self-report instruments may be useful in differentiating recurrent-episode major depression from dysthymic disorders.

Adult↗

Treatment of retinal detachment with congenital optic pit by krypton laser photocoagulation.

Five patients with a congenital pit of the optic nerve and serous detachment of the macular retina were treated with krypton laser photocoagulation to the juxtapapillary region in an attempt to induce resolution of the retinal detachment. The subretinal fluid resolved after laser therapy in four of the patients. In the fifth, the retinal detachment was successfully treated with pars plana vitrectomy. One patient developed a macular hole and decreased visual acuity, despite resolution of the subretinal fluid.

Adolescent↗

Cleavage from the N-terminal region of beta Bp crystallin during aging of the human lens.

Polyclonal antisera have been made to synthetic peptides that correspond to the N-terminal (residues 1-12) and C-terminal (residues 195-204) sequences of bovine beta Bp crystallin. Both anti-beta Bp1-12 and anti-beta Bp195-204 recognize specifically the beta Bp component of bovine lens. In the young human lens, anti-beta Bp195-204 recognizes predominantly the 26,000 MW form of beta Bp, while in older lenses this same antiserum recognizes mainly the 22,000 MW in vivo proteolysis product. In contrast, during aging of the normal human lens anti-beta Bp1-12 recognizes only decreasing amounts of the 26,000 MW form of beta Bp, with no binding to the 22,000 MW form of this polypeptide. These results suggest that during aging of the normal human lens, the N-terminus of beta Bp is the preferred site of in vivo proteolysis.

Adolescent↗

Taking the measure of anxiety and depression. Validity of the reconstructed Hamilton scales.

The ability of the Hamilton Psychiatric Rating Scale for Depression (HRSD) and the Hamilton Anxiety Rating Scale (HARS) to discriminate major depressive disorder (MDD) from generalized anxiety disorder (GAD) was studied in 120 psychiatric outpatients and cross-validated with another 71 outpatients. Factor and discriminant analyses were used to develop revised anxiety and depression scales that were less positively correlated with each other, showed greater internal consistency, and differentiated MDD and GAD better than the original scales. The recombined scales also displayed higher rates of correctly assigning the samples to these disorders than did the original scales.

Adult↗

The expression of 3-fucosylated-N-acetyl lactosamine carbohydrate determinants in renal tumours.

The distribution in renal tumours of 3-fucosyl-N-acetyl lactosamine has been studied by using the monoclonal antibodies AGF 4.36 and AGF 4.48 and immunoperoxidase methods on tissue sections. Seven of 19 nephroblastomas and 12 of 30 renal cell carcinomas contained the epitope. In nephroblastomas the epitope was found on the terminals of type B tubules in six cases and in one case on the type A or neoplastic tubules. In renal carcinoma the antigen was found on the surface of tumour cells. The results suggest that in kidneys bearing nephroblastomas ureteric bud elements may grow into the tumour from the adjacent kidney.

Antibodies, Monoclonal↗