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Biomedical subjects

N Berry

Publications and source records attributed to N Berry.

At least 55 records · Page 3Linked to original sources
PubMed1990

Protein kinase C and T cell activation.

Understanding the intracellular mechanisms by which binding of ligands, such as hormones and growth factors, to their specific receptors elicits the appropriate cellular response has long been a topic of great interest. Considerable excitement was generated when it was recognised that several receptor-ligand interactions operate via the hydrolysis of inositol phospholipids. This yields, at least, two 'second messengers', namely, inositol 1,4,5-trisphosphate [Ins(1,4,5)P3], which causes the release of Ca2+ from intracellular stores, and 1,2-diacylglycerol (ac2Gro), which activates the serine/threonine-specific enzyme, protein kinase C(PKC), reviewed in [1] and [2]. The pertinent question that follows is, how do PKC activation and elevation of the intracellular Ca2+ concentration evoke cell responses? In this review, attention has been focused on PKC, and the consequences of its activation in resting human T cells. Evidence that PKC activity is, at least partially, responsible for activation of resting human T cells will be examined, and some of the more recent research investigating how PKC activation elicits this cell response will be described.

Animals↗
PubMed1990

Activation of resting human T cells requires prolonged stimulation of protein kinase C.

Purified resting human T cells can be induced to express the alpha subunit of the interleukin 2 receptor and to proliferate by treatment with 12-O-tetradecanoylphorbol-13-acetate plus ionomycin but not with 1,2-dioctanoylglycerol plus ionomycin. Determination of the translocation of protein kinase C showed that 12-O-tetradecanoylphorbol-13-acetate plus ionomycin caused a prolonged membrane association of the enzyme for more than 4 hr, whereas 1,2-dioctanoylglycerol plus ionomycin induced a transient membrane association, which was maximal at 20 min. Delivery of multiple additions of 1,2-dioctanoylglycerol plus ionomycin to the T cells resulted in progressively increased expression of the alpha subunit of the interleukin 2 receptor and proliferation commensurate with the number of multiple additions delivered, suggesting that prolonged protein kinase C activity is required for T-cell activation.

Cell Membrane↗
PubMed1989

Human T cell activation by phorbol esters and diacylglycerol analogues.

Activation of protein kinase C (PKC), by the phorbol ester PMA, or the membrane-permeable diacylglycerol 1-oleoyl 2-acetylglycerol (OAG), had different effects on the proliferation-associated responses of a more than 99% pure population of human T cells. Treatment with PMA or OAG caused down-regulation of the TCR-CD3 complex, but only PMA, in combination with ionomycin, was capable of stimulating IL-2R expression and proliferation. Immunocytochemical staining with antisera specific for the PKC subspecies alpha, beta I, beta II, and gamma showed that untreated resting T cells normally coexpress alpha, beta I, and beta II PKC subspecies, which are distributed diffusely throughout the cell, with some localization around the periphery of the nucleus. There was no difference between the responses of these PKC subspecies to OAG and PMA, redistributing, after 10 min of treatment, to a discrete focal area within the cell. Treatment with OAG resulted in transient redistribution of PKC, maximal at 10 min, while in PMA-stimulated cells, the PKC redistribution was prolonged, persisting for at least 24 h. The results suggest that the difference in cellular response to treatment with PMA and OAG is not a consequence of differential activation of various PKC subspecies.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1989

Expression of protein kinase C subspecies in human leukemia-lymphoma cell lines.

Expression of protein kinase C (PKC) subspecies was studied in various human leukemia-lymphoma cell lines. The PKC in most cell lines examined was resolved into two major fractions corresponding to type II (beta-sequence) and type III (alpha-sequence) PKC of the rat brain. The amounts of these two subspecies greatly varied among the cell lines. Type I PKC (gamma-sequence) was expressed in none of the cell lines tested, but PKCs with undefined structures were frequently detected. The differential co-expression of several PKC subspecies is presumably related to the state of cell differentiation.

Animals↗
PubMed1988

Differential down-regulation of protein kinase C subspecies in KM3 cells.

The down-regulation of protein kinase C (PKC) subspecies in KM3 cells (a pre-B, pre-T cell line) has been examined. The PKC from KM3 cells was resolved into two subspecies, type II (mainly beta II) and type III (alpha), upon hydroxyapatite column chromatography. Biochemical and immunocytochemical analysis revealed that, when these cells were treated with 12-O-tetradecanoylphorbol 13-acetate (TPA), the time course of down-regulation of the PKC subspecies was different; type II PKC was translocated and depleted from the cell more quickly than type III enzyme. The results suggest that each PKC subspecies plays a different role in the cellular response to TPA and probably to other external stimuli.

Cell Compartmentation↗
PubMed1988

Isolation of protein kinase C subspecies from a preparation of human T lymphocytes.

Using a preparation of purified human T lymphocytes, we were able to resolve a partially purified protein kinase C (PKC) enzyme fraction into two distinct subspecies, of approximately equal activity. Biochemical and immunocytochemical analysis revealed that these fractions closely resembled the type II (beta) and type III(alpha) PKC subspecies previously identified and characterised from brain tissue. These results provide valuable information for further studies on the role of individual PKC subspecies in T lymphocyte proliferation.

Calcium Chloride↗
PubMed1988

Potentiation of anti-carcinoembryonic antigen immunotoxin cytotoxicity by monoclonal antibodies reacting with co-expressed carcinoembryonic antigen epitopes.

The initial step in ricin A-chain (RTA)-immunotoxin-mediated cell cytotoxicity involves binding to the target cell Ag through the antibody moiety. One of the factors influencing this is the affinity of the antibody component for the target cell Ag. Multiple epitopes on carcinoembryonic Ag have been mapped providing a range of mAb of known specificity. These have been used to show that the cytotoxicity of an immunotoxin containing RTA conjugated to an anti-carcinoembryonic Ag mAb (228-RTA) is potentiated by mAb recognizing different epitopes. The potentiating antibodies also increased the level of target cell binding of antibody 228. Cross-linking of cell bound antibody was not involved because monovalent fragments of a potentiating antibody were effective. The potentiating antibodies modified the binding affinity of 228 antibody increasing the t1/2 of antibody at the tumor cell surface. This increased the dwell time of cell bound antibody and using conjugates of 228 linked to albumin-tetramethylrhodamine it was shown to enhance conjugate endocytosis. These investigations indicate that enhanced antibody affinity leads to increased endocytosis of bound immunoconjugate and potentiates cytotoxicity.

Adjuvants, Immunologic↗
PubMed1988

Comparison of the detection of breast carcinoma metastases by routine histological diagnosis and by immunohistochemical staining.

The detection of metastases in 371 axillary lymph nodes by immunohistochemical staining and by routine histological examination was compared in the surgically removed tissue from 50 consecutive patients with breast carcinoma. The primary tumour and axillary lymph nodes were stained with three monoclonal antibodies directed against epitopes of the human milk fat globule (HMFG1; HMFG2; E29), and an anticytokeratin antibody (CAM 5.2), in a double-bridge immunoalkaline phosphatase staining technique. Metastases revealed by further sectioning through the tissue were identified before the immunohistological comparison. The use of immunohistochemical staining resulted in an increased detection of metastases in both infiltrating ductal carcinoma (13.1%) and infiltrating lobular carcinoma (37.5%), an overall increase of 17.3%. The follow-up data over a minimum period of 2 years is available for these patients.

Adenocarcinoma↗
PubMed1987

Isoelastic uncemented hip arthroplasty--early experience.

With the increasing failure rae with time of cemented total hip arthroplasty there is a growing interest in uncemented total joint replacement. This review of 88 Isoelastic total hip arthroplasties, and 28 Isoelastic hemiarthroplasties suggests that this implant gives results comparable with cemented total hip arthroplasty at a similar time. The Isoelastic hip replacement system uses uncemented components that have been designed to closely approximate the biomechanical properties of the bone into which they are implanted. The surgical technique is demanding, and orthopaedic surgeons who anticipate using uncemented implants should receive thorough training before embarking on an implantation.

Elasticity↗
PubMed1985

Paget's disease of the nipple. Immunohistochemical localization of milk fat globule membrane antigens.

The authors have used the indirect immunoperoxidase technique to examine the presence and distribution of milk fat globule membrane antigens in 12 cases of mammary Paget's disease using two monoclonal antibodies, HMFG-1 and HMFG-2. These stain breast epithelial cells but do not stain normal epidermis. The Paget's cells showed a similar pattern of cytoplasmic staining to that seen in the underlying intraduct or invasive carcinoma, therefore confirming them to be malignant ductal cells. To support this one of the cases was stained with the antibody LE 61 which is specific for nonepidermal epithelial cytokeratins. The result was strongly positive in Paget's cells in the epidermis but not in squamous cells.

Antibodies, Monoclonal↗
PubMed1985

The prognostic value of the monoclonal antibodies HMFG1 and HMFG2 in breast cancer.

The monoclonal antibodies HMFG1 and HMFG2 identify antigens of the milk fat globule membrane which are also found on breast epithelial cells. Immunohistochemical staining was performed using both antibodies on formalin fixed, paraffin embedded sections of 93 breast carcinoma, 36 histologically benign lesions and 29 histologically normal breast tissue blocks. In both normal and benign breast disease the staining was largely extracellular whilst in malignant tissue the staining was variable and often intracellular. Nine carcinomas did not stain with either antibody. The staining patterns of malignant tissues were graded and no correlation was found between the grades and survival or indices of prognosis, (the oestrogen receptor status, Bloom's grade and the presence or absence of metastases to the axillary nodes.) This study indicates that with the present methods available for grading staining patterns, although of diagnostic value, these monoclonal antibodies are unlikely to assist in determining either the degree of tumour differentiation or prognosis in breast carcinoma.

Antibodies, Monoclonal↗
PubMed1982

Psychological factors in breast feeding versus bottle feeding in the Third World.

Some readers may be aware of the sociopolitical and moral issues associated with the theme of Brenda Meldrum's article (Bulletin, June 1982) about breast and bottle feeding in the 3rd world. For over a decade many groups (e.g. War on Want; World Development Movement) have been concerned that unnecessary bottle feeding has almost certainly resulted in considerable infant disease and mortality in the 3rd world. Morever, such groups have been well aware of the high psychological value of formula foods; and have attributed this mainly to the aggressive and fundamentally dishonest way in which food companies promote their breastmilk substitutes. In 1979, in response to the bad publicity resulting from the campaigning of 3rd world agencies, Nestle and others agreed to adopt a voluntary code of practice proposed by World Health Organization and UNICEF. However, commercial interests have prevailed--baby food sales in 3rd world account for 2 1/2% of 1 transnational group's turnover--and the malpractices have continued. In view of this we feel that it is appropriate to amend Brenda Meldrum's conclusion to: While transnational corporations continue to actively promote their baby food products in the 3rd world, there can be no reversal to the old, exclusive breastfeeding of traditional practice, and that infants that would otherwise have lived will continue to die. The boycott campaign is continuing and might we suggest that BPS members who organize conferences give some thought to the possibility of requesting that their caterers do not use products of these companies. A list of companies may be obtained from New Internationalist (February 1982) or from us.

Advertising↗
PubMed1980

An evaluation of a rehabilitation workshop.

Staff awareness of the steps involved in rehabilitation was assessed before and after a multidisciplinary workshop concerned with the aims, methods and principles of rehabilitation in psychiatry. Results were compared with similar assessments derived from a matched control group which was not exposed to any educational programme. The data suggest severe limitations in staff performance on the rehabilitation problem solving task which was used. Performance was not improved by the workshop, and the limitations of staff opinion as measures of the educational value of the workshop were clearly demonstrated. These results are consistent with other findings, and demonstrate the need to evaluate educational programmes provided in the Health Services.

Evaluation Studies as Topic↗