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Biomedical subjects

J J Murphy

Publications and source records attributed to J J Murphy.

At least 109 records · Page 6Linked to original sources

Coupling of early response gene expression to distinct regulatory pathways during alpha-interferon and phorbol ester-induced plasmacytoid differentiation of B chronic lymphocytic leukaemia cells.

Phorbol esters (phorbol 12-myristate 13-acetate; PMA) and alpha-interferon (alpha-IFN) act through divergent signal transduction pathways to induce B chronic lymphocytic leukaemia cells (B-CLL) to undergo plasmacytoid differentiation in vitro. By using a panel of PMA-inducible early response gene probes we show that these two different effectors are coupled to second messenger pathways that do not converge on a common gene regulatory programme in differentiation of B-CLL cells. Moreover, using the calcium ionophore, A23187, four distinct regulatory classes of early response gene could be defined implying that multiple regulatory pathways may mediate the process of terminal differentiation in B lymphocytes.

B-Lymphocytes↗

Patterns of nuclear proto-oncogene expression during induced differentiation and proliferation of human B chronic lymphocytic leukaemia cells.

Phorbol ester-induced differentiation of human B-chronic lymphocytic leukaemic cells was found to be preceded by a rapid transient induction in expression of the c-jun proto-oncogene, which paralleled that of c-fos. Induced expression of c-myc but not of c-fos/c-jun proto-oncogenes was markedly higher in a proliferating variant leukaemic cell population compared with that seen in typical lymphocytic leukaemia cells. These data suggest that the c-fos/c-jun nuclear oncogenes play a role in induced differentiation, whilst c-myc is more important in the proliferative response of B lymphocytes.

B-Lymphocytes↗

Abnormalities in T-cell associated rearrangement of T-cell receptor gamma chain genes in B-cell chronic lymphocytic leukemia.

Non-random rearrangement of genes encoding the gamma chain of the T-cell antigen receptor is known to occur in a developmentally regulated fashion during thymocyte differentiation. We show here that peripheral blood T lymphocytes from patients with B-cell chronic lymphocytic leukemia display marked abnormalities in the spectrum of gamma variable region gene rearrangements compared with normal peripheral blood. Of seven patients studied, all displayed a reduction of rearrangements into V9 (subgroup V II), while two cases had, in addition, over-representation of specific rearrangements involving subgroup V I; one V 2/4, the other V 5. These observations have a number of implications relevant to mechanisms of disease pathogenesis, and may provide new insight into the basis of T-cell dysfunction that is frequently associated with this condition.

Blotting, Southern↗

Findings at necropsy in the heart of a patient with anticardiolipin syndrome.

A 40 year old man with a history of myocardial infarction and hypertension presented with transient cerebral ischaemic attacks, aortic regurgitation, a raised erythrocyte sedimentation rate, and thrombocytopenia. The anticardiolipin syndrome was diagnosed and he was treated with prednisolone and warfarin. He died two years later after the development of acute heart failure. At necropsy his heart showed widespread arteriolar thrombosis without vasculitis, recanalised large vessel occlusion, and a "post-inflammatory" valvulitis of the aortic valve.

Adult↗

Randomised double-blind placebo-controlled trial of feverfew in migraine prevention.

The use of feverfew (Tanacetum parthenium) for migraine prophylaxis was assessed in a randomised, double-blind, placebo-controlled crossover study. After a one-month single-blind placebo run-in, 72 volunteers were randomly allocated to receive either one capsule of dried feverfew leaves a day or matching placebo for four months and then transferred to the other treatment limb for a further four months. Frequency and severity of attacks were determined from diary cards which were issued every two months; efficacy of each treatment was also assessed by visual analogue scores. 60 patients completed the study and full information was available in 59. Treatment with feverfew was associated with a reduction in the mean number and severity of attacks in each two-month period, and in the degree of vomiting; duration of individual attacks was unaltered. Visual analogue scores also indicated a significant improvement with feverfew. There were no serious side-effects.

Adult↗

25- to 30-nm virus particle associated with a hospital outbreak of acute gastroenteritis with evidence for airborne transmission.

Between November 1 and 22, 1985, an outbreak of acute, nonbacterial gastroenteritis occurred in a 600-bed hospital in Toronto, Ontario, Canada. Illness in 635 of 2,379 (27%) staff was characterized by fatigue, nausea, diarrhea, and vomiting and had a median duration of 24-48 hours. The finding of virus-like particles measuring 25-30 nm in six stool specimens and low rates of seroresponse to Norwalk virus (3/39) and Snow Mountain agent (1/6) suggest that a Norwalk-like virus was responsible for the outbreak. The outbreak was of abrupt onset and high incidence, affecting 79 people in a single day. No common food or water exposure could be identified. The attack rate was greatest (69%) for staff who had worked in the Emergency Room. Of 100 patients and their companions who visited the Emergency Room on November 11-12 for unrelated problems, 33 (33%) developed gastroenteritis 24-48 hours after their visit, versus 0 of 18 who visited the Emergency Room on November 8 (p less than 0.001). An analysis of housekeepers who worked at least once during the period from November 9-13, which included those who became ill during the period of November 9-14, showed that the risk of becoming ill was four times greater for those who visited or walked through the Emergency Room than for those who did not (p = 0.028). These data are consistent with the possibility of the airborne spread of a virus.

Adult↗

Failure of dopexamine to maintain haemodynamic improvement in patients with chronic heart failure.

Ten patients with chronic heart failure were given a continuous infusion of dopexamine after an initial stage of dose titration. On the dose selected the cardiac index initially rose by 56%, as a result of an increase in both heart rate and stroke volume index. Systemic vascular resistance fell by 34% and the mean arterial pressure did not change. Within 18 hours of the start of the continuous infusion, however, all the variables except heart rate had returned to preinfusion values. Nine of the 10 patients were withdrawn from the 48 hour study, six because of haemodynamic deterioration and two because of side effects. If the premature loss of therapeutic effect reflects an intrinsic property of this agent, dopexamine may be of limited clinical value.

Adrenergic Agonists↗

Mobile nylon bag for estimating intestinal availability of rumen undegradable protein.

The objective was to develop a method for estimating intestinal availability of rumen undegradable protein. One-gram samples of six feedstuffs were placed into small (3.5 X 5.5 cm) nylon bags (pore size 48 micron). Bags were heat sealed and ruminally incubated in a polyester mesh (lingerie) bag in quadruplicate for each of six time periods (0, 2, 4, 8, 12, 24 h). Two bags from each rumen incubation time were inserted into the small intestine via a duodenal cannula at the rate of one bag per 45 min. Bags were mechanically washed either upon removal from the rumen--for determination of rumen degradability, or when recovered from the feces--for estimation of intestinal availability. Dried bags plus contents were digested intact for nitrogen analysis. Rumen degradable protein and apparent intestinal availability of undegradable protein (based on 8 h of rumen incubation) for corn gluten meal, fish meal, meat and bone meal, soybean meal, canola meal, and alfalfa hay, respectively, were 11.8, 95.0; 28.5, 82.8; 46.7, 73.0; 55.1, 99.3; 69.7, 79.2; and 68.8, 71.2. Results support the use of this technique as a rapid method for estimating both ruminal degradability, and intestinal availability of rumen undegradable protein.

Animals↗

Effect of protein concentration and protein source on the degradability of dry matter and protein in situ.

Degradability of DM and CP was determined in situ for barley, canola meal, corn gluten meal, barley silage, and four concentrate mixtures. Crude protein percent of concentrate mixtures 1 to 4, respectively, were barley plus canola 1, 15.1; barley plus canola 2, 21.0; barley plus corn gluten 1, 17.1; and barley plus corn gluten 2, 19.6. Degradability of each feedstuff was measured on each of four basal diets consisting of barley silage and one of the above concentrate mixtures fed in the proportion 40:60 (DM). The resulting CP percent of diets containing concentrates 1 to 4 were 12.3, 16.1, 13.8, and 16.4. Effective degradability for DM and CP, assuming a rumen outflow rate of .08 h-1, were: barley 77.7 and 79.8; canola meal 60.9 and 66.6; corn gluten meal 18.9 and 11.0; barley silage 47.0 and 81.1; barley plus canola 1, 76.4 and 77.4; barley plus canola 2, 72.5 and 71.8; barley plus corn gluten 1, 72.8 and 55.8; barley plus corn gluten 2, 70.2 and 47.4. With two exceptions (DM degradability of concentrate 4 and CP degradability of concentrate 2), basal diet had no significant effect on effective CP or effective DM degradability. Crude protein degradability of concentrate mixtures 1 to 4, respectively, as measured (77.4, 71.8, 55.8, and 47.4) was similar to degradability estimated on the basis of their ingredient content (75.7, 72.1, 49.6, and 43.0).

Animal Feed↗

Analysis and isolation of leukaemic and residual normal B lymphocyte populations from patients with chronic lymphocytic leukaemia.

Two colour fluorescent staining using anti-Leu-1 and anti-B1 monoclonal antibodies has been combined with continuous flow microfluorimetry to analyse and isolate the T and B cell populations in B cell chronic lymphocytic leukaemia (B-CLL) patients. In Rai stage 0 patients two distinct B1 positive populations were detected and sorted; one was Leu-1- and the other Leu-1+. Analysis of the isolated populations showed that the former (Leu-1- B1+) represented the residual normal B cells, whereas the latter represented monoclonal CLL B cells. Short term culture of these cells in vitro showed that the Leu-1+ B1+ population secreted IgM, but not IgG, following PMA stimulation.

Antibodies, Monoclonal↗

Expression of functional interleukin 2 receptors on chronic lymphocytic leukaemia B lymphocytes is modulated by recombinant interleukin 2.

In 16 of 18 chronic lymphocytic leukaemia (CLL) patients examined, a significant proportion of B cells in the leukaemic clone bound monoclonal antibodies specific for the interleukin 2 (IL-2) receptor site (CD25). B lymphocytes from patients tested showed a direct response to recombinant interleukin (rIL-2) during culture in vitro as shown by: (a) a ligand-mediated upregulation in the level of IL-2 receptor (IL-2R) expression (12 of 12 patients), (b) an increase in cell size (eight of nine patients), (c) an increase in 3H-thymidine uptake (four of six patients). Taken together, this evidence suggests that the majority of leukaemic B cells from all the CLL patients examined expressed functional IL-2 receptors in vitro. Intriguingly, maximal receptor upregulation or increase in cell size was achieved at a lower concentration (50 u/ml) of rIL-2 than was required to achieve maximal 3H-thymidine incorporation.

B-Lymphocytes↗

Membrane damage by hemolytic viruses, toxins, complement, and other cytotoxic agents. A common mechanism blocked by divalent cations.

Hemolytic viruses, bacterial and animal toxins, the components of activated complement, cationic proteins, and detergents induce a sequence of permeability changes at the plasma membrane that are in every case sensitive to changes in ionic strength and to divalent cations. Individually, each agent exhibits positive cooperativity; when two agents are present together, they show synergy. It is concluded that such cytotoxic agents damage membranes by a common mechanism. Hence permeability changes are unlikely to depend on the formation of specific, protein-lined channels, as previously envisaged in the case of activated complement or certain bacterial toxins.

Animals↗