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Biomedical subjects

F Lancaster

Publications and source records attributed to F Lancaster.

11 recordsLinked to original sources
PubMed2000

Persistence of clonal T-cell expansions following high-dose chemotherapy and autologous peripheral blood progenitor cell rescue.

Analysing the regeneration of T lymphocytes after high-dose chemotherapy with autologous peripheral blood progenitor cell rescue (PBPCR) may help elucidate the mechanisms of immune recovery. The T-cell receptor variable beta chain (TCRBV) repertoire of adult patients undergoing high-dose chemotherapy was analysed by flow cytometry, before and after treatment. Four patients were found to have a stable expansion present (TCRBV3, 17, 21 and 22) ranging from 8% to 42% of the CD4(+) or CD8(+) repertoire. We demonstrated that, in these patients, following high-dose chemotherapy and autologous stem cell transplantation, the clonal expansions reappeared in peripheral blood and returned to pretransplant levels. Three expansions (CD3(+)CD8(+)TCRBV3(+), CD3(+)CD4(+)TCRBV21(+) and CD3(+)CD8(+)TCRBV22(+)) were further defined by sequence analysis of the complementarity-determining region (CDR)3 portion within the TCR rearrangements. These were shown to be predominantly clonal, with the same sequences being identified in peripheral blood before and after PBPCR, providing evidence that the overwhelming majority of T cells in these expansions arise from mature lymphocytes. This study demonstrated that patients undergoing autologous PBPCR for high-dose chemotherapy regenerate clonal expansions, consistent with pretreatment levels. They also regenerate T-cell repertoires with each TCRBV family represented to a similar level as that prior to high-dose chemotherapy.

Amino Acid Sequence↗
PubMed1995

Influence of laparoscopic and conventional cholecystectomy upon cell-mediated immunity.

Surgery, trauma and anaesthesia induce a state of transient immunosuppression. Laparoscopic cholecystectomy has several well documented clinical advantages over traditional cholecystectomy and provokes a lower acute phase response, thought to be a result of the smaller wound size. The influence of laparoscopic cholecystectomy (21 patients) and conventional open cholecystectomy (13 patients) upon components of the cell-mediated immune system was investigated. Cell-mediated immunity was studied by in vitro assays of T lymphocyte proliferation to different mitogens, and by natural killer cell cytotoxicity using a standard 51Cr release assay. Blood samples were taken before and 24 h after the start of the operation. In the sample taken after operation there was significant depression of T lymphocyte proliferation to phytohaemagglutinin (stimulation index 149.4 versus 33.3, P < 0.002), staphylococcal enterotoxin B (85.2 versus 52.6, P = 0.01) and toxic shock syndrome toxin (48.4 versus 14.8, P = 0.08) in the group of patients who underwent open surgery, but not in the group treated by laparoscopic surgery. There was a small but statistically insignificant decrease of natural killer cell cytotoxicity in both groups of patients. These findings suggest that laparoscopic cholecystectomy causes less depression of cell-mediated immunity than open cholecystectomy.

Adult↗
PubMed1993

Reduction in circulating levels of CD4-positive lymphocytes in acute pancreatitis: relationship to endotoxin, interleukin 6 and disease severity.

The proportion of peripheral blood mononuclear cells expressing the T helper cell phenotype and levels of antiendotoxin core antibody, interleukin (IL) 6 and C-reactive protein (CRP) were determined within 48 h of admission in a group of 29 patients with acute pancreatitis (16 mild, 13 severe attacks). There was a significant decrease in the proportion of T helper cells (12.2 versus 34.9 per cent, P < 0.01) and significant increases in levels of IL-6 (69.5 versus < 10 pg/ml, P < 0.01) and CRP (119 versus 30.5 mg/l, P < 0.01) in severe compared with mild attacks. During the convalescent stage at 3 months after admission, severe attacks were characterized by a significant increase in the proportion of T helper cells compared with the acute period (22.4 versus 10.6 per cent, P < 0.01). A persistently low proportion of T helper cells was associated with residual pancreatic necrosis. The presence of circulating endotoxin was demonstrated in two mild and two severe attacks using the Limulus amoebocyte lysate assay, and abnormal levels of antiendotoxin core antibodies were found in 70 and 92 per cent of mild and severe attacks respectively. There was a strong inverse correlation between levels of CRP and the proportion of T helper cells in severe disease (r = -0.76, P = 0.004). Translocation of endotoxin from the gastrointestinal tract may partly explain the abnormal levels of T helper cells, IL-6 and CRP.

Acute Disease↗
PubMed1991

Gamma delta T cell receptor-positive cells of the human gastrointestinal mucosa: occurrence and V region gene expression in Heliobacter pylori-associated gastritis, coeliac disease and inflammatory bowel disease.

T cells expressing the gamma delta heterodimer of the T cell receptor (TCR) were studied with respect to their occurrence and expression of gamma delta TCR variable region (V) genes in the normal gastrointestinal mucosa and in a variety of inflammatory conditions. In controls, gamma delta TCR+ cells were a minority population confined to the epithelial compartment of stomach, small bowel and colonic mucosae. Unlike in the periphery, gastro-intestinal gamma delta TCR+ intraepithelial lymphocytes (IEL) were mainly V delta 1+ (89.98 +/- 17.70%); few were V delta 2+ (6.04 +/- 13.8%) or V gamma 9+ (11.38 +/- 10.73%). All gamma delta TCR+ IEL were CD5low; nearly half were CD8+ and the remainder were CD4-CD8- 'double negatives'. There was no significant change from normal in percentages of gamma delta TCR+ IEL in H. pylori-associated gastritis, Crohn's disease and ulcerative colitis. However, in coeliac disease, gamma delta TCR+ IEL were elevated from 2.54% (+/- 1.71) in controls to 29.6% (+/- 16.1) in untreated patients (P less than 0.001) and 18.5% (+/- 7.2) in treated patients (P less than 0.001) and more were CD4-CD8-. Otherwise, gamma delta TCR+ IEL phenotypes were little changed: the majority remained V delta 1+V delta 2-V gamma 9- and all were CD5low. These data suggest that increased gamma delta TCR+ IEL are not a generalized response to intestinal inflammation or to stress proteins, although the typical V delta 1+V delta 2-V gamma 9- CD5low phenotype is retained.

Adult↗
PubMed1989

Synaptic density of caudate-putamen and visual cortex following exposure to ethanol in utero.

Pregnant Long-Evans rats were fed a liquid diet containing ethanol (30% of total calories) during days 3-19 of gestation. Controls were given ad libitum access to liquid diet lacking ethanol, or pair-fed isocaloric amounts based on consumption by the animals in the ethanol group. Brain development of female offspring was evaluated by analysis of electron micrographs of caudate-putamen and visual cortex. Numbers of presynaptic terminals and synaptic junctions (synaptic density) per unit area were compared for 14- and 28-day-old offspring of dams from the three treatment groups. Synaptic density of the caudate-putamen and visual cortex was not affected by ethanol at 14 or 28 days. Although exposure to ethanol during a period comparable to the first two trimesters of human development with minimal or no undernutrition did not affect numerical density of synapses in visual cortex or caudate-putamen, synaptogenesis of caudate-putamen was altered in offspring of pair-fed animals.

Animals↗
PubMed1987

Prenatal ethanol exposure decreases synaptic density in the molecular layer of the cerebellum.

Pregnant Long-Evans rats were fed a liquid diet containing ethanol during gestation (peak blood ethanol level of 128 mg/dl). Pairfed dams were given isocaloric diet lacking ethanol; and control dams were allowed ad libitum access to liquid diet without ethanol. Subsequent effects of ethanol were measured by morphometric analysis of electron micrographs. Tissue samples from the molecular layer of the cerebellum (sixth lobule) were stained with ethanolic-phosphotungstic acid (E-PTA) and synaptic junctions were counted. Numbers of synaptic junctions per unit area were compared for 14 and 28 day old offspring of ethanol treated, pairfed or control dams. Synaptic density of the molecular layer of the sixth cerebellar lobule was decreased in 28 day old animals which were exposed prenatally to ethanol.

Animals↗
PubMed1987

Voluntary beer drinking in rats.

Female Long-Evans rats (N = 30) were tested for individual preference for beer for a 24 h period and then assigned to beer (BR) (N = 15) or control (CT) (N = 15) groups according to preference. BR animals were allowed ad libitum access to beer, food and water; while CT animals were allowed ad libitum access to food and water for a 21 day period. Beer, food and water consumption levels were recorded daily. Animals were weighed every other day. Blood alcohol levels and pattern of drinking (comparison of beer consumption in light versus dark cycles) were measured in a separate set of animals. At the end of 21 days of drinking, beer was withdrawn from the BR group and all animals were observed for withdrawal symptomology. BR animals ate more food than CT animals days 2 through 13, and then ate less than CT on days 17 through 21. BR animals drank more "total water" (drinking water plus water in beer) than CT. Body weights were not affected. Changes in body temperatures and tail flick latency, and notation of hyperactivity, shivering and tremoring during 8 hours of withdrawal indicated that BR animals were dependent on alcohol.

Alcohol Drinking↗
PubMed1986

Fetal ethanol exposure: a morphometric analysis of myelination in the optic nerve.

Pregnant Long-Evans rats were fed a liquid diet containing ethanol during gestation. Controls consisted of both pair-fed dams and dams fed ad libitum with an equivalent, iso-caloric diet lacking ethanol. Subsequent effects of ethanol measured in the offspring include a significant lag in the rate at which non-myelinated axons are lost in association with the initial overproduction of neurons. Additionally, there was a slight lag in the rate of acquisition of myelinated axons; and altogether there was a large increase in the ratio of non-myelinated to myelinated axons. Frequency spectra of myelinated and non-myelinated axons by size were normal, and the relationship between axon size and myelin lamellae was also normal. Measured against the dynamic, normal background of rapid cell-loss and the progressive development of myelin, morphometric demonstration and evaluation of the comparatively small divergences associated with fetal alcohol exposure are difficult: nevertheless, these results are consistent with and help account for the marginal hypomyelination previously observed by quantitative neurochemistry.

Animals↗
PubMedDate not supplied

Anti-idiotypic T cells suppress rejection of renal allografts in rats.

Kidney allografts between inbred rats differing at the major histocompatibility complex (MHC) are normally rejected, usually within 10 to 12 days. In many strain combinations, however, permanent graft acceptance can be induced by either immunological enhancement or a short course of immunosuppressive chemotherapy. In both cases, prolonged graft survival is accompanied by the appearance in the spleen of a population of suppressor cells. When transferred to a syngeneic host, these cells abrogate or strikingly diminish the rejection response elicited by a renal allograft of the same genotype as the original kidney donor. We have now examined the properties of these suppressor cells and have detected a subpopulation that proliferates in vitro when stimulated by irradiated syngeneic T blasts reactive to MHC alloantigens of the kidney donor strain. Comparable proliferation, however, is not induced either by syngeneic blasts reactive to a third strain or by polyclonal syngeneic blasts. These results support the hypothesis that this subpopulation is anti-idiotypic, with specificity for the idiotypes carried by syngeneic T cells stimulated by the kidney allograft. Such anti-idiotypic cells could function as suppressors.

Animals↗