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Biomedical subjects

M Moore

Publications and source records attributed to M Moore.

At least 343 records · Page 19Linked to original sources

Reaction times and attention in Parkinson's disease.

Ten patients with Parkinson's disease performed a simple reaction time task in which, on hearing a tone, they pressed a button with the left thumb. In the first experiment tones sometimes occurred unannounced and at other times were preceded (by between 0 and 3200 ms) by a warning signal. The second experiment was identical to the first except that the subject had simultaneously to perform a simple continuous task with his right hand. Patients had slower reaction times than controls under all circumstances. In general, however, the effect of a warning signal and the effect of a second task were the same for both groups. In the control group the effect of a warning signal depended on whether or not a second task was being performed. Specifically, the advantage of a warning signal for reaction time was lost after long intervals (greater than 200 ms) when a second task was being performed. Parkinson's disease patients lost this advantage even when they were not performing a second task. Animal studies have suggested that dopamine deficiency results in an increase in neural "noise" in the basal ganglia. The behavioural consequences of this may be that Parkinson's disease patients always perform as if they were carrying out another task at the same time. In contrast, their ability to benefit from a warning signal and to allocate attentional resources are unimpaired.

Adult↗

Functional heterogeneity among cytotoxic clones derived from natural killer cells.

Clones were obtained from highly purified populations of human peripheral blood natural killer (NK) cells propagated in the presence of interleukin-2 and phytohaemagglutinin. Almost all clones were cytotoxic against standard NK targets and many were also able to kill the B lymphoblastoid cell line BSM. This latter property was not necessarily a result of the incorporation of this cell line into the feeder mixture used to derive the clones. In most cloning experiments there was a high degree of concordance between the killing of the NK targets K562 and Molt 4 by panels of clones. In some cases this extended to the killing of BSM targets but in other instances there was no relationship or even an inverse correlation between killing of BSM and other targets. In a single cloning experiment there was no relationship between killing of BSM and Raji targets. In some cases a panel of clones could be divided into two or more distinct groups based on their differential activity towards BSM and K562. Such differences were not solely due to inter-donor variation. These findings were extended by cold target inhibition experiments in which at least three types of clone were identified. In one group of clones, which was nonreactive towards BSM, cold BSM significantly enhanced the killing of K562 in a dose-dependent fashion. These experiments provide evidence for a limited degree of functional heterogeneity among clones derived from human peripheral blood NK cells.

Clone Cells↗

Production of interferon and tumour necrosis factor by cloned human natural cytotoxic lymphocytes and T cells.

Cell lines and clones, derived from natural killer (NK) cell-enriched (B73.1+) peripheral blood lymphocytes (PBL) from several human donors, that expressed distinct surface phenotypes and were cytolytically active against K562 target cells were tested for their capacity to produce interferon (IFN) and tumour necrosis factor (TNF), IFN and TNF were measured firstly in biological assays and secondly in specific immunoassays for alpha-IFN, gamma-IFN and tumour necrosis factor (TNF alpha). It was found that the majority of NK-derived lines and clones were highly cytotoxic towards K562, but generally produced relatively low or undetectable levels of gamma-IFN and TNF alpha following stimulation with phytohaemagglutinin. No alpha-IFN was detected in supernatants from these cells. In comparison, cell lines and clones, derived from T lymphocyte (B73.1-) enriched PBL from the same donors were poorly cytotoxic towards K562, but generally produced higher levels of gamma-IFN and TNF than NK-derived cells. Thus, neither gamma-IFN nor TNF production were shown to correlate well with the capacity of NK-derived or T cell clones to effect cytotoxic action towards K562 in vitro. These results suggest that the co-production of gamma-IFN and TNF is not indicative of cytotoxic potential.

Antigens, Surface↗

The role of Na-hylan in reducing postsurgical tendon adhesions: Part 2.

Na-hylan, a chemically modified sodium hyaluronate jelly, was studied mechanically and histologically as a surgical device to diminish tendon adhesions in rabbit extensor hallucis longus tendons after severe surgical trauma. Na-hylan jelly of high viscoelastic properties was found to be highly effective in decreasing tendon adhesions. Na-hylan jelly of low viscoelastic properties was not effective in diminishing adhesion formation. There was no interference with the tensile strength of tendon healing, and no evidence of acute or chronic inflammatory response to the Na-hylan jelly.

Administration, Topical↗

Epidural butorphanol or morphine for the relief of post-cesarean section pain: ventilatory responses to carbon dioxide.

To determine the safety, efficacy, and the ventilatory responses to carbon dioxide (CO2) of epidurally administered butorphanol or morphine, 122 healthy women who underwent cesarean section with epidural anesthesia were studied. Patients were randomly assigned to receive one of four epidural regimens for the relief of postoperative pain: 5 mg morphine (n = 32), 4 mg butorphanol (n = 30), 2 mg butorphanol (n = 29), or 1 mg butorphanol (n = 31). Epidural morphine provided satisfactory analgesia with slow onset and long duration of approximately 21 hr. When butorphanol was administered, analgesia of rapid onset was seen with increasing duration and effectiveness observed with increasing dose; approximately 8 hr when using 4 mg. Sixty-two percent of the patients who received morphine had pruritus. Somnolence was the main side effect encountered in patients who received epidural butorphanol. The ventilatory response to CO2 was depressed after morphine and after 2 and 4 mg butorphanol, but the duration of depression was more prolonged after morphine. It is concluded that epidural butorphanol is effective in providing pain relief after cesarean section with minor side effects. However, patients must be observed closely because of possible respiratory depression.

Butorphanol↗

Expression of myeloid differentiation antigens on myeloblasts in bone marrow of patients with myelodysplastic syndromes.

Bone marrow myeloblasts in 15 patients with myelodysplastic syndromes were quantitated with monoclonal antibodies using the immunoalkaline phosphatase technique. Positive blasts were identified in 7 of the 15 cases with at least one of three antibodies reactive with acute myelomonocytic leukaemic cells (PMN-6, PMN-29, AML 2-23) which were non-reactive with normal myeloblasts. In 5 of these cases increased PM-81 positivity was associated with expression of at least one of the other antigens (PM-81 antibody reacts with all types of acute myeloid leukaemic cells and a certain percentage of normal myeloblasts). The data suggest an aberration of myeloid differentiation in myelodysplastic syndromes which is reflected in altered surface marker features.

Antibodies, Monoclonal↗

Vasopressin antagonism in the squirrel monkey (Saimiri sciureus).

Vasopressin antagonism and water diuresis (aquaresis) is demonstrated after i.p. or i.v. administration of vasopressin antagonists in a primate species, the squirrel monkey (Saimiri sciureus). Antagonism of vasopressin-stimulated renal medullary adenylate cyclase activity was evaluated in vitro; the most potent antagonists were those with D-tyrosine (alkyl) substitutions at position 2. Aquaresis was evaluated in vivo; the most potent aquaretic agents were again those with D-tyrosine (alkyl) substitutions at position 2. Correlation of in vitro vasopressin antagonist and in vivo aquaretic potencies for a series of antagonists was r = 0.7880 (P less than .05). Renal excretion of electrolytes, creatinine and urea tended to increase slightly as a function of vasopressin antagonist dose; the rates of solute excretion approached but seldom exceeded those rates associated with water diuresis in squirrel monkeys. The vasopressin antagonists antagonized the antidiuretic activity of exogenous vasopressin in vivo. Onset of the aquaretic response to i.v. administration of desGlyd(CH2)5D-Tyr(Et)VAVP was within 30 min; duration was greater than 120 min. These studies establish vasopressin antagonism and aquaresis associated with administration of vasopressin antagonists in a primate species.

Adenylyl Cyclases↗

Expression of HLA-D sub-region products on human colorectal carcinoma.

The major histocompatibility complex (MHC) status of normal, inflamed, pre-malignant and malignant epithelia of the human gastrointestinal tract was investigated by immunocytochemical methods using monoclonal antibodies (MAbs) directed against heavy (alpha)- and light (beta 2m)-chain Class-I molecules and sub-locus products (DP, DQ, DR) of the HLA-D region. Class-I expression on epithelial cells appeared to vary little with pathological status except in the case of 4/32 (13%) colorectal carcinomas in which the antigens were undetectable or scanty. The pattern of Class-II expression was more complex. The antigens were readily detectable on normal stomach epithelium, in villous adenomas and in inflammatory bowel mucosa. In each of these situations DR was the predominant specificity, followed by DP and DQ. Expression on normal colonic epithelium was usually negative but, in the vicinity of a neoplasm or an area of marked leukocyte infiltration, Class-II molecules (DR greater than DP much greater than DQ) were detectable. A similar pattern of non-coordinate expression was found on 23/32 (72%) colorectal carcinomas, but on the remaining 28% no Class-II products were detectable, under conditions wherein stromal leukocytes were strongly stained. The data suggest that in a significant proportion (nearly 30%) of primary colorectal carcinomas, the capacity for Class-II induction, a constitutive or acquired feature of normal colorectal epithelium, is either diminished or lost. Also, tumor Class-II status is not correlated to Dukes' stage or differentiation.

Adenoma↗

Ca2+ homeostasis and cytotoxicity in isolated hepatocytes: studies with extracellular adenosine 5'-triphosphate.

The incubation of isolated rat hepatocytes with extracellular adenosine 5'-triphosphate (ATP) resulted in an inhibition of Ca2+ efflux. The ATP-induced Ca2+ accumulation as determined by the increase in phosphorylase a activity and the Ca2+-sensitive fluorescent indicator (2-[(2-bis-[carboxymethyl]-amino-5-methylphenoxy)-methyl]-6-methoxy-8- bis-[carboxymethyl]aminoquinoline-tetrakis-[acetoxymethyl]ester) (Quin 2-AM) was associated with both the hydrolysis of ATP and the phosphorylation of a 110 kDa protein. No significant alteration in the intracellular ATP level was observed. The appearance of surface blebs and cytotoxicity followed the rise in cytosolic Ca2+, suggesting that the increased free Ca2+ may be responsible for the loss of viability. When a calmodulin inhibitor, 1-[bis(4-chlorophenyl)methyl]-3-[ 2-(2,4-dichlorophenyl)-2-[(2,4-dichlorophenyl)methoxy] ethyl]-1H- imidazolium chloride (calmidazolium), was included in the medium prior to ATP addition, bleb formation was reduced and the loss of viability was completely prevented, indicating that a Ca2+-calmodulin process may be involved in the initiation of cytotoxicity.

Adenosine Triphosphate↗

The effect of alphanapthylthiourea (ANTU)-induced acute injury on lung binding of antibody to angiotensin converting enzyme (ACE).

The effects of ANTU-induced acute pulmonary capillary injury on lung and serum ACE functional activity and the specific accumulation of radio-labelled anti-ACE in lung were explored. Rats were injected either with ANTU or the solvent and sacrificed at various intervals up to one week after injection. All ANTU-injected animals developed pulmonary edema and bilateral pleural effusions which resolved by the one week time point. At no time was there any significant change in serum ACE levels. The specific activity of total lung ACE however rose from 11.0 +/- .95 (mean +/- SEM) to 18.4 +/- 1.1 by two hours after ANTU; by 24 hours, however, solubilized lung ACE had fallen significantly to 6.9 +/- .79 (p less than .01). Total lung ACE had returned to control values by one week. In parallel groups of animals the accumulation of 125I-labelled anti-ACE (AA) or normal sheep immunoglobulin (NSG) was compared in control and ANTU-treated rats. The ratio of the radioactivity in the lungs of AA--injected animals to that in NSG--injected animals fell significantly after ANTU administration (5.0 +/- .88 to 1.2 +/- .28 at 2 hours) suggesting that immunoreactive ACE had fallen despite an increase in ACE functional activity. The decreased binding of AA at the early time points perhaps reflects internalization of endothelial cell ACE in response to injury and an inability of the antibody to interact with the enzyme. The reduction in binding at 24 hours (1.38 +/- .47) correlates with a reduction in total lung ACE. ANTI-ACE may be a useful reagent for quantitating endothelial cell damage following lung injury.

Animals↗

Proliferative and cytotoxic responses of human peripheral blood lymphocytes to autologous malignant effusions. An analysis at the clonal level.

Peripheral blood lymphocytes from five patients were stimulated initially in mixed lymphocyte:tumour culture (MLTC) with autologous malignant effusions and cloned by limiting dilution in interleukin-2 prior to phenotyping and assay for different functional capabilities namely proliferative responsiveness to autologous and allogeneic tumours in the primed lymphocyte test (PLT) and cytotoxicity (CTX) toward a range of fresh tumour and cell line targets. For individual clones the two functional activities tended to be mutually exclusive. Clones (or 'cloids' containing more than one PLT precursor) from three of four tumours analysed were responsive to autologous tumour cells in the PLT of which two shared antigens with allogeneic tumours of similar tissue provenance. All phenotyped PLT positive clones were T3+T4+T8-. Cytotoxic clones were generated from all MLTCs. Their target cell repertoire (based on an analysis of greater than 30) was generally broad including cell lines sensitive to natural killer (NK) cells, and less frequently and to a weaker extent, fresh autologous and allogeneic tumours. An ovarian carcinoma was exceptional, insofar as the CTX of 8/9 clones was apparently restricted to the autologous tumour. Phenotypically cytotoxic clones were T3+T4-T8+, less usually T3+T4+T8-, but invariably B73.1- (a monoclonal antibody reactive with the peripheral blood NK subset). Analysis at the clonal level emphasises the diversity of responses to putative human tumour-associated antigens, and the need to identify the critical functionally active molecules in the MLTC.

Aged↗

Lymphokine activated killing of fresh human leukaemias.

The relative susceptibility of 10 human leukaemias comprising acute phase leucocytes from 5 acute myeloid and 5 lymphoid neoplasms, and 2 immunoblastic lymphomas to killing by peripheral blood mononuclear cells (PBMC), before and after target cell treatment with phytohaemagglutinin (PHA), and by interleukin-2 (IL-2) activated peripheral blood lymphocytes (PBL) was investigated in short term 51Cr release assays using effector cells from 10 allogeneic donors. Optimal lectin-dependent cellular cytotoxicity (LDCC) was verified against K562 and L1210 cells and lymphokine-activated killing (LAK) against K562 and Daudi cells. Under these conditions, the majority of the leukaemias tested revealed only a finite sensitivity to any of the cytotoxic mechanisms, which was dependent on the donor origin of the effectors. The leukaemias were more consistently susceptible to LDCC than LAK and removal of adherent cells to enrich for the latter activity in effector populations, was ineffective. Lymphocytes from a patient in long term (greater than 5 yr) remission exhibited LAK against the autologous target E84, a natural killer (NK)-sensitive acute myelomonocytic leukaemia. These cells failed to cross-compete for lysis of K562 by LAK cells, suggesting the existence of different recognition structure(s) on the two targets.

Cell Line↗

Studies of the enhancement of natural cytotoxicity by the streptococcal immunopotentiator OK432.

The immunopotentiator OK432, a product of Streptococcus pyogenes A3, enhanced the natural killer (NK) activity of unseparated human peripheral blood mononuclear cells (PBM) and separated, nonadherent lymphocytes (PBL) containing less than 0.5% contamination with monocytes. Following treatment with OK432, both unseparated and non-adherent cell preparations produced interferon (IFN) alpha and gamma and low levels of interleukin-2 (IL-2). However, in the presence of neutralising amounts of anti-IFN alpha and gamma antisera, the NK enhancing effect of OK432 was not fully inhibited. Filtered supernatants derived from OK432-treated PBM or PBL also enhanced the NK activity of fresh PBM. In this instance, in most experiments, the NK enhancing effect of supernatants (from non-adherent cells) was fully inhibited by anti-IFN antisera. However, in some experiments, enhancement of NK activity by anti-IFN antisera-treated supernatants was still found. It is suggested that the presence of IL-2 or, possibly, other as yet uncharacterized factors secreted following OK432 treatment, account for this residual enhancement of NK activity.

Antibodies↗

A new immunoassay using monoclonal antibodies HMFG1 and HMFG2 together with an existing marker CA125 for the serological detection and management of epithelial ovarian cancer.

A new method with a low pH step to dissociate serum complexes has been developed to measure serum levels of antigens associated with ovarian cancer. The antigens are detected by monoclonal antibodies HMFG1 and HMFG2 and have been compared to an existing ovarian cancer associated antigen detected by the antibody CA125. Elevated HMFG1 was found in 56%, and elevated HMFG2 in 65% of 924 sera from 85 patients with ovarian cancer. CA125 was elevated in 85% of these sera. When the three markers were used in conjunction, 95% of sera from patients with ovarian cancer were positive--compared with 7% in sera from healthy control subjects. Therefore, the combination of HMFG1, HMFG2 and CA125 increases the diagnostic accuracy. If all three markers are normal in a patient previously treated for ovarian cancer then no further positive information regarding disease status can be obtained by ultrasound and CT scanning.

Antibodies, Monoclonal↗

Growth and development in the haemopoietic system: the role of lymphokines and their possible therapeutic potential in disease and malignancy.

Some cells can produce soluble factors which modify the behaviour and/or growth pattern of other cells. These 'factors' are broadly referred to as cytokines and may be further classified on the basis of the cells which were first characterized as the producer cells. For example, lymphokines are the soluble products of lymphocytes and monokines are the soluble factors released by mononuclear phagocytes. Although useful, this nomenclature is in many respects misleading since protein sequence and gene structure analysis has shown that 'lymphokines' may not only be produced by lymphocytes, but by various other types of cells as well. Fortunately, with the advent of molecular techniques, the number of cytokines has decreased drastically and what was once an increasingly large number of factors is now becoming restricted to a manageable few. What remain, however, still pose conceptual and mechanistic problems. These have mainly arisen as a result of the assay systems used to detect and define the lymphokines and the problems in extending the findings to normal physiology. Almost exclusively, lymphocytes have been stimulated to produce and export their soluble factors in response to nonphysiologic stimuli, such as lectins, and the various lymphokines have been characterized on the basis of in vitro test systems. Therefore, for reasons which will become obvious later, many of the in vitro findings have been difficult to corroborate in in vivo situations. Nonetheless, the results obtained with these factors are sufficiently intriguing to warrant serious consideration regarding their relevance in normal haemopoiesis, their possible therapeutic potential and their involvement in disease.

Cell Line↗

Intubating conditions following pre-induction priming with alcuronium.

Three priming doses of alcuronium have been investigated and, using a logistic transformation technique, the priming dose required to produce adequate intubating conditions in 99% of patients at 60 seconds following the second dose of alcuronium has been deduced. This dose, 106.5 micrograms/kg is extremely high and may be unsafe if used, since 30% of our patients complained of side effects when given a priming dose of only 50 micrograms/kg.

Adult↗