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Biomedical subjects

F Brennan

Publications and source records attributed to F Brennan.

33 records · Page 2Linked to original sources
PubMed1990

Interleukin 7 and interleukin 4 stimulate human thymocyte growth through distinct mechanisms.

One of the major functions of cytokines is their ability to regulate cell growth and differentiation. The complexity of this process has been highlighted by recent studies on murine thymocytes; it has been shown that a number of cytokines interact to regulate thymocyte growth. We have investigated the effects of interleukin 4 (IL-4) and interleukin 7 (IL-7) on human thymocyte proliferation. Although maximal proliferation was dependent upon the presence of the mitogen phytohaemagglutinin (PHA), IL-7 alone stimulated thymocyte growth. In order to determine if this proliferation was due to the induction of IL-2, this pathway was inhibited by the addition of blocking antibody to the IL-2 receptor. Proliferation induced with IL-7 plus PHA, but not that induced by IL-7 alone, could be blocked by this treatment. In contrast, IL-4 stimulated thymocyte proliferation only in the presence of PHA; this proliferation was not inhibited by antibodies to the IL-2 receptor. Our findings show that both IL-7 and IL-4 can act as growth factors for human thymocytes, and that these cytokines stimulate proliferation through distinct mechanisms.

Cell Division↗
PubMed1990

Granulocyte-macrophage colony stimulating factor induces both HLA-DR expression and cytokine production by human monocytes.

The effect of recombinant human granulocyte-macrophage colony stimulating factor (GM-CSF) on the expression of HLA-DR, and the production of the cytokines interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha) by human peripheral blood monocyte-enriched populations was investigated. GM-CSF was shown to induce both the expression of HLA-DR and the cytokines IL-1 and TNF alpha in a dose-dependent manner. In contrast, interferon-gamma (IFN-gamma), which induced major histocompatibility complex (MHC) class II expression, did not induce IL-1 or TNF alpha production. However, IFN-gamma enhanced the cell surface expression of HLA-DR and the production of IL-1 and TNF alpha on monocyte-enriched cells stimulated by GM-CSF. By itself, GM-CSF did not induce surface class II expression on the human monocytic tumour cell line THP-1, whereas it synergized with IFN-gamma to induce surface expression. These cells responded to GM-CSF by producing IL-1 and TNF alpha; Northern blotting showed that mRNA levels of IL-1 and TNF alpha were transiently induced, similar to other cytokines. Our results indicate that GM-CSF is a major macrophage activating factor that is capable of inducing both the expression of HLA-DR and the cytokines involved in T-cell activation by macrophages; therefore, GM-CSF may be of importance in potentiating antigen presenting function.

Blotting, Northern↗
PubMed1989

Persistence of collagen type II-specific T-cell clones in the synovial membrane of a patient with rheumatoid arthritis.

Rheumatoid arthritis is an autoimmune disease characterized by T-cell infiltration of the synovium of joints. Analysis of the phenotype and antigen specificity of the infiltrating cells may thus provide insight into the pathogenesis of rheumatoid arthritis. T cells were cloned with interleukin 2, a procedure that selects for in vivo-activated cells. All clones had the CD4 CDW29 phenotype. Their antigen specificity was tested by using a panel of candidate joint autoantigens. Four of 17 reacted against autologous blood mononuclear cells. Two clones proliferated in response to collagen type II. After 21 months, another set of clones was derived from synovial tissue of the same joint. One of eight clones tested showed a strong proliferative response against collagen type II. The uncloned synovial T cells of a third operation from another joint also responded to collagen type II. The persistence of collagen type II-specific T cells in active rheumatoid joints over a period of 3 years suggests that collagen type II could be one of the autoantigens involved in perpetuating the inflammatory process in rheumatoid arthritis.

Arthritis, Rheumatoid↗
PubMed1989

Coordinate expansion of 'fetal type' lymphocytes (TCR gamma delta+T and CD5+B) in rheumatoid arthritis and primary Sjögren's syndrome.

In the blood of 10 patients with rheumatoid arthritis (RA), the number of TCR gamma delta+T cells and CD5+B cells was 5.5% +/- 4.38 and 34.3% +/- 20.62 (mean +/- s.d.), respectively. In 12 patients with primary Sjögren's syndrome (SS) the mean +/- s.d. of these T and B cell subpopulations was 4.75% +/- 3.85 and 38.75% +/- 22.68. These values were significantly increased as compared with the circulating T and B cells from 22 healthy subjects in whom TCR gamma delta+T cells were 2.09 +/- 1.01 (P less than 0.001 for RA; P less than 0.004 for SS) and CD5+B cells were 18.09% +/- 4.47 (P less than 0.001 for RA and SS). This increase was not influenced by disease activity. Furthermore, there was a marked correlation (P less than 0.001) between the levels of TCR gamma delta +T cells and CD5+B cells. This novel finding of coordinate elevated levels of lymphocytes with fetal phenotypes in RA and primary SS suggests an immunological imbalance that may have implications in these diseases.

Antigens, Differentiation↗
PubMed1989

Medium and long-term complications of endoscopic sphincterotomy for choledocholithiasis.

The medium and long-term complications of endoscopic sphincterotomy for choledocholithiasis were examined in patients referred to an endoscopy centre in an area general hospital. One hundred and thirty-eight patients were reviewed between 6 months and 7 years after successful endoscopic sphincterotomy for choledocholithiasis. The procedure was carried out post-cholecystectomy in 69 (50%) and with the gallbladder in situ in 69 patients. Four post-cholecystectomy patients and 10 with intact gallbladders had died by the time of review. A postal questionnaire was completed by the remaining 124 patients. Sixty-two post-cholecystectomy and 49 with gallbladders still intact remained symptom-free at follow-up. Eight patients had had the sphincterotomy as a preliminary to cholecystectomy. There were persistent symptoms in three post-cholecystectomy and two with intact gallbladders. Medium to long-term complications are uncommon after endoscopic sphincterotomy for choledocholithiasis.

Adult↗
PubMed1988

Role of HLA class II and cytokine expression in rheumatoid arthritis.

HLA class II expression is notable in rheumatoid arthritis. We have investigated the mechanism of HLA class II regulation in the joints and found local synthesis, as judged by mRNA levels to be high. The role of antigen presentation in maintaining class II mRNA was explored, and blocking presentation by using monoclonal antibodies to HLA class II inhibited synthesis of mRNA for HLA-DR alpha chain. HLA class II expression is maintained by cytokines and so cytokine production in rheumatoid joints was investigated. It was chosen to use mRNA analysis by slot blotting as a screening assay, and the expression of many cytokines was detected. Levels of these were maintained in culture in the absence of extrinsic stimulation.

Antibody Formation↗
PubMed1983

Nifedipine in the treatment of hypertension.

Nifedipine, a calcium antagonist with a predominant vasodilator action, was evaluated for the treatment of hypertension. A 20 mg-tablet, with a slower absorption and a more sustained blood-level than provided by the 10 mg-capsule was administered to 20 patients. The duration of the trial was 20 weeks. All patients achieved a significant reduction in both systolic (p less than 0.05) and diastolic (p less than 0.001) blood-pressure (B.P.), but 10 patients were withdrawn before completion of the trial period. Two patients, although achieving a fall in B.P. which was significant, did not reach to target level (less than 160/90) on maximal dosage, one patient suffered a stroke due to a cerebral infarct, and seven patients were withdrawn because of side-effects due mainly to vasodilatation. The remaining 10 patients obtained a satisfactory response. In nine patients, who had achieved a satisfactory result, there was no change in plasma renin activity (P.R.A.) during chronic nifedipine administration.

Absorption↗
PubMed1983

Calcium and phosphorus metabolism during total parenteral nutrition.

Calcium and phosphorus metabolism and balance were studied in 151 patients receiving total parenteral nutrition (TPN). Hypercalciuria was common, with mean (+/- SD) urinary calcium excretion 17.5 +/- 3.9 meq/24 hours (n = 2610). There was a significant positive correlation between urinary calcium excretion and parenteral calcium intake (r = 0.34, p less than 0.001). There was also a positive correlation between calcium balance and parenteral calcium intake (r = 0.61, p less than 0.001) in patients without extra-renal losses. Positive calcium balance was achieved with parenteral calcium intake greater than 15 meq/24 hours. Urinary phosphorus excretion correlated positively with parenteral phosphorus intake (r = 0.50, p less than 0.001). Phosphorous balance also correlated positively with parenteral phosphorus intake (r = 0.78, p less than 0.001). Positive phosphorus balance was achieved with parenteral phosphorus intake above 15 mmol/24 hours. Fifty-three patients received 1,000 IU vitamin D once weekly and showed no significant change in serum calcium. Ninety-eight patients received 1,000 IU vitamin D twice weekly and showed a gradual but significant mean increase over time in serum calcium.

Adolescent↗
PubMedDate not supplied

Benchmarking best practice for external ventricular drainage.

Sharing of best practice and use of all available evidence is important in developing effective clinical guidelines for nursing practice. This can be achieved through benchmarking. Sharing of good practice and achieving consensus guidelines can avoid repetition of effort by nurses engaged in similar fields of practice. The Pan London Neuroscience Practice Development Forum was established in 1998 to share best practice within the field of neuroscience nursing across London. The Pan London Forum has now achieved consensus and developed evidence-based clinical guidelines for the management of external ventricular drainage. Within the scope of this article, the principles of external ventricular drainage will be highlighted, before identifying the evidence base for nursing management of patients. Approaches for troubleshooting common problems will also be discussed and the benchmarked clinical guidelines will be presented.

Benchmarking↗
PubMedDate not supplied

Primary malignant melanoma of the meninges.

A case of primary malignant melanoma of the meninges is described in which the clinical presentation is that of visual loss and limb weakness. Clinically a diagnosis of carcinomatous meningitis was made and subsequently malignant cells were found in the cerebrospinal fluid (CSF). At autopsy the diagnosis of primary malignant melanoma of the meninges was made.

Diagnosis, Differential↗