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Biomedical subjects

M Banks

Publications and source records attributed to M Banks.

At least 55 records · Page 3Linked to original sources

Expression and activity of signaling molecules in T lymphocytes obtained from patients with metastatic melanoma before and after interleukin 2 therapy.

Recent studies have demonstrated altered expression and function of signaling molecules in T and natural killer cells in patients with cancer. The impairment of immune cell functions in advanced cancer may result from defects in signal transduction. We studied purified T cells obtained from peripheral blood or tumor-involved lymph nodes (LNs) of 45 patients with advanced metastatic melanoma for the presence of abnormalities in expression or activity of various signaling molecules. Western blot analyses demonstrated reduced expression of CD3-zeta in 10 of 11 preparations of T cells obtained from tumor-involved LNs. Similar reduction in expression of CD3-zeta was demonstrated by immunostaining performed in situ on frozen sections of melanoma tissues. Expression of p56(lck) and Zap-70, but not phospholipase C-gamma1, was reduced in these patients' T cells relative to those obtained from normal individuals. In 50% of the patients, reduced expression of CD3-zeta and p56(lck) was observed in T lymphocytes obtained both from tumor-involved LNs and from peripheral blood. To determine whether deficient expression of these signaling molecules is reversible, T cells from melanoma-involved LNs were incubated in the presence of interleukin 2 (IL-2) for 48 h, and lysates from fresh or cultured lymphocytes were compared for changes in expression of signaling molecules. Cells cultured in the presence of IL-2 demonstrated increased expression of CD3-zeta and p56(lck), which approached the levels detected in normal T cells. However, the level of p56(lck) kinase activity did not normalize in any of the LN-derived lymphocytes cultured in the presence of IL-2. Decreased expression of CD3-zeta or p56(lck) observed in the patients' T cells was not reversed by immunotherapy with IL-2 at low or high dose in those patients with metastatic melanoma who failed to respond to therapy. However, in three patients who achieved clinical responses, the initially reduced expression of zeta in peripheral blood T cells normalized following IL-2 therapy.

Humans↗

Soluble interleukin-5 receptor alpha-chain binding assays: use for screening and analysis of interleukin-5 mutants.

Interleukin-5 (IL-5) is a key cytokine for the production, differentiation, and activation of eosinophils. IL-5 is a member of the four helical bundle family of cytokines, and in common with many members of the cytokine family it binds to a heterodimeric receptor composed of a ligand binding alpha-chain and a signal-transducing beta-chain. We have established two receptor/ligand binding assays based on the extracellular domain of the receptor alpha-chain which we have produced as a fusion protein. One assay is based on scintillation proximity fluoromicrospheres and radiolabeled ligand and the other on detection of biotinylated ligand binding to immobilized receptor using a chemiluminescent substrate in a 96-well microtiter plate format. Both receptor binding assays have been optimized for high throughput screening for receptor antagonists. These assays were also used for analytical purposes and the binding of ligand to the receptor alpha-chain was compared directly to receptor binding assays performed on TF-1 cells which express the receptor alpha beta-heterodimer. These three assays have been used to study site-directed mutants of IL-5 to determine the important residues for interaction of the cytokine with each chain of the receptor (P. Graber et al. (1995) J. Biol. Chem. 270, 15762-15769).

Animals↗

Identification of key charged residues of human interleukin-5 in receptor binding and cellular activation.

Interleukin-5 (IL-5) is a cytokine that plays a major role in the differentiation and activation of eosinophils. In order to identify which charged residues of human IL-5 are important in binding to its receptor and subsequent cellular activation, we have systematically replaced all of the clusters of charged amino acids with alanine residues. The mutants have been expressed in Escherichia coli, renatured, and purified. They were assayed for ability to cause proliferation of the erythroleukaemic cell line TF-1 and the up-regulation of eosinophil adhesion to ICAM-1. In addition, we studied receptor binding using either immobilized recombinant IL-5 receptor alpha-chain or the alpha/beta-receptor complex expressed on TF-1 cells. The key charged residue involved in binding to the beta-chain of the receptor is Glu-12. This residue is in an identical position to those previously identified in IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF) involved in binding to the receptor beta-chain. The alpha-chain binding site is shown to involve the side chains Arg-90 and Glu-109, located in the second beta sheet and after the end of the fourth helix, respectively. It is unique to IL-5 and does not occur in IL-3 or GM-CSF. Understanding the topology of the interaction of IL-5 with its receptor chains will help in the search for rationally designed antagonists of IL-5 function.

Amino Acid Sequence↗

Carboplatin and ifosfamide and selective consolidation in advanced seminoma.

This prospective phase II study assesses the clinical efficacy and complications of a treatment regimen comprising combination chemotherapy with carboplatin and ifosfamide and selective consolidation in advanced seminoma. Of 43 patients who entered the study, between May 1989 and May 1992, 42 were evaluable. 30 achieved a complete remission (71%; 95% confidence interval, 56-84%) after chemotherapy alone. 10 achieved a complete remission (24%; 95% confidence interval, 13-39%) after chemotherapy plus consolidation. 38 of the 42 patients (91%; 95% confidence interval, 83-98%) remained in remission after a median follow-up period of 35 months (20-56 months). No patient experienced nephrotoxic, neurotoxic, or ototoxic effects, or haemorrhagic cystitis. Ten per cent of the patients had leucopenic fever requiring hospitalisation. Twenty-four per cent required platelet transfusions, and 26% required transfusions of packed red blood cells. For patients with seminoma, treatment with carboplatin and ifosfamide and selective consolidation is safe and effective.

Adolescent↗

Brain osmolyte content and blood-brain barrier water permeability surface area product in osmotic edema.

Brain edema was induced in adult rats by intraperitoneal injection of distilled water equivalent to 15% of the animal's body weight. Mean +/- SEM serum osmolality fell from 291 +/- 3 mOsm to 253 +/- 4 mOsm during the next hour while cerebral gray matter water content increased from 79.5 +/- 0.2% to 80.9 +/- 0.2%. Gray matter content of sodium, potassium, taurine, glycine, glutamine, and glutamate were unchanged. However, the blood-brain barrier permeability/surface area product for water decreased by 40%. This alteration in water permeability may represent a response to limit water influx during the first hour of hypoosmotic brain edema.

Animals↗

Effects of gender and listeners' preference on magnitude-estimation scaling of rock music.

The purpose of the present study was to examine the effects of gender and listener preference on magnitude-estimation scaling of rock music. Four groups of young adults were tested: 14 women who liked rock music, 14 women who disliked rock music, 14 men who liked rock music, and 14 men who disliked rock music. Subjects were instructed to assign numerical values to a random series of nine suprathreshold intensity levels of a 10-sec. sample of rock music. Analysis indicated that there was no difference in scaling performance between women and men. There was a difference in scaling performance between the group of women who liked rock music and the group of women who disliked rock music. There was no difference in the way the two groups of men performed the scaling task. These results suggest that men and women perform magnitude-estimation scaling of rock music similarly. Women, however, allow preference to influence how they choose numbers during magnitude-estimation scaling tasks whereas men do not.

Adolescent↗

Effect of personality on magnitude-estimation scaling of complex auditory stimuli.

The purpose of the present study was to examine the effect of the personality trait of extraversion/introversion on magnitude-estimation scaling of complex auditory stimuli. Two groups of subjects, 10 who liked rock music (M age = 22.4 yr.) and 10 who disliked rock music (M age = 21.9 yr.), were tested. Subjects were instructed to assign numerical values to a random series of nine suprathreshold intensity levels of a 10-sec. sample of rock music. Each subject was given the Eysenck Personality Inventory, a test designed to measure the personality trait of extraversion/introversion. Statistical analyses indicated that the personality trait of extraversion/introversion did not appear to have an effect on the way the subjects scaled the rock-music stimulus.

Adolescent↗

Lingual vibrotactile magnitude-estimation scaling using a limited set of suprathreshold stimulus intensities.

The purpose of the present study was to assess feasibility of lingual vibrotactile suprathreshold testing with a limited number of intensities. 25 subjects ranging in age from 18 to 26 years (M = 19 yr.) participated. Two magnitude-estimation scaling tasks were presented to each subject with 1 wk. between tasks. One magnitude-estimation task involved eight suprathreshold intensities and the other involved four. Statistical analyses showed that there was no difference in subjects' responses to the two scaling efforts. In pure research endeavors it might make sense to continue to obtain as many magnitude-scaling data points as possible, but practical prudence may dictate a limited set of suprathreshold intensities for efficiency and subjects' comfort.

Adolescent↗

Aujeszky's disease ELISA using baculovirus expressed glycoproteins.

The genes coding for two Aujeszky's disease virus glycoproteins, gp50 and gIII, were amplified by PCR and inserted into a baculovirus transfer vector. Following co-transfection of insect cells with a modified wild type baculovirus, recombinant virus clones expressing the inserted glycoproteins were detected by ELISA. These clones were then amplified and the expressed products used as the antigen for an ELISA to detect antibodies to Aujeszky's disease virus in pig sera.

Animals↗

Locomotion of aged rats: relationship to neurochemical but not morphological changes in nigrostriatal dopaminergic neurons.

Spontaneous locomotion and motor coordination was evaluated in young (5-6 month old) and aged (24-25 month old) rats. Animals were tested for spontaneous locomotor activity in Digiscan Animal Activity Monitors during the nocturnal cycle. Aged animals exhibited a significant hypoactivity compared to their young counterparts. Evaluation of the time course of activity revealed that the young animals had a cyclical pattern of activity during the 12-hour testing period with clear peaks at 2-4 hours after the initiation of testing and at 8- to 10-hour intervals thereafter. In contrast, the aged animals exhibited a blunted initial activity peak. During the remainder of the test period the aged animals activity was stable with no further peaks in activity. Compared to the young animals the aged animals also (a) remained suspended from a horizontal wire for less time, (b) were unable to descend a wooden pole covered with wire mesh in a coordinated manner, (c) fell more rapidly from a rotating rod and (d) were unable to maintain their balance on a series of wooden beams with either a square or rounded top of varying widths. Histological analysis demonstrated that there was no reduction in the number, area, or length of tyrosine hydroxylase-immunoreactive neurons within the A8, A9, or A10 region of the aged animals. Neurochemical analysis revealed that while DA and HVA levels were not decreased in the aged rats, DOPAC levels, as well as the ratios of DA/DOPAC and DA/HVA, were decreased. These results indicate that neurochemical but not morphological changes within the nigrostriatal dopaminergic system underlie the deficits in motor behavior observed in aged rats.

Aging↗

The effect of preference for rock music on magnitude-estimation scaling behavior in young adults.

The purpose of the present study was to examine the effect of preference for rock music on magnitude-estimation scaling behavior in young adults. Two groups of young adults, 20 who liked rock music and 20 who did not like rock music, were tested. Subjects were instructed to assign numerical values to a random series of nine suprathreshold intensity levels of a 10-second sample of rock music. Analysis indicated that there was a difference in performance by the two groups of subjects on the magnitude-estimation scaling task. The subjects who liked rock music provided significantly lower mean numerical responses than the subjects who did not like rock music for all nine suprathreshold intensities.

Adolescent↗

Effect of preference for rock music on magnitude-production scaling behavior in young adults: a validation.

The purpose of the presence study was to examine the effect of preference for rock music on magnitude-production scaling behavior in young adults as an attempt to validate further the 1993 magnitude-estimation scaling results obtained by Fucci, Harris, Petrosino, and Banks. Two groups of young adults, 20 who liked rock music and 20 who disliked rock music, were tested. Subjects were instructed to adjust the intensity of a 10-sec. sample of rock music in response to seven written stimuli presented in random order. Analysis indicated that there was a significant difference in performance by the two groups of subjects on the magnitude-production scaling task. Those subjects who liked rock music adjusted the intensity of the music to higher levels than did the subjects who disliked rock music.

Adolescent↗

Elevated levels of prostaglandin E2 in the liver of rats fed a choline deficient diet: possible involvement in liver tumor promotion.

The effect of feeding a choline deficient (CD) diet, an efficient liver tumor promoting regimen, on the prostaglandin metabolism in the liver of male Sprague-Dawley rats was investigated. The possible biological significance of the alteration was examined using hypolipidemic peroxisome proliferators and modifiers of prostaglandin metabolism such as indomethacin and menhaden oil in the short term assay of the induction of enzyme altered foci in the liver. A CD diet, when fed for 10-30 days, induced 2-2.5 times increases in the levels of prostaglandin E2 (PGE2) in the liver, while the hypolipidemic peroxisome proliferators, 4-chloro-6(2,3-xylidino) pyrimidinylthio(N-hydroxyethyl)-acetamide (BR931) and di(2-ethylhexyl)-phthalate (DEHP), markedly reduced the levels of this metabolite. The addition of BR931 or indomethacin to a CD diet suppressed the diet-induced elevations of PGE2 and a substitution of fats in a CD diet with menhaden oil had the same effect. Furthermore, both indomethacin and menhaden oil added to a CD diet suppressed the induction of gamma-glutamyltranspeptidase positive hepatocyte foci in the liver of rats initiated with a single dose of diethylnitrosamine after 8 weeks of the dietary promotion. The results suggest that altered prostaglandin metabolism may be involved in the liver tumor promoting effect of a CD diet.

Animals↗

Aujeszky's disease ELISA: cross-reactions with other herpesvirus antisera.

The production of antibodies in pigs to 11 herpesviruses was investigated in relation to their ability to cross-react with Aujeszky's disease virus (suid herpesvirus 1--SHV1). Of the herpesviruses tested only two, sheep herpesvirus (caprine herpesvirus 1) and dog herpesvirus (canid herpesvirus 1), failed to produce homologous virus antibodies. Only the antibodies to bovine herpesvirus 1 (BHV1) produced a cross-reaction by SHV1 enzyme-linked immunosorbent assay (ELISA). No SHV1 neutralizing antibodies were detected in any of the herpesvirus antisera. A cross-reaction with SHV1 by a serum from a pig naturally infected with BHV1 or with any of the other herpesviruses tested was considered unlikely.

Animals↗

Regulation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity in mouse uterine epithelial cells.

The regulation of 3-hydroxy-3-methylglutaryl-CoA reductase was studied in mouse uterine epithelium. The enzyme was rapidly inactivated during incubation with ATP/Mg2+ in vitro, and could be re-activated by incubation with partially purified rat liver phosphoprotein phosphatase. Enzyme activity was rapidly inhibited by mevalonate injection in vivo to approx. 30% of control. The percentage of total enzyme active in vivo was measured by inclusion of NaF in the isolation buffers. The percentage of enzyme active in vivo 18 h after stimulation by oestrogens remained at approx. 25% after inhibition of activity by mevalonate injection, cholesterol feeding or progesterone pretreatment. However, 9 h after oestrogen stimulation, cholesterol feeding inhibited enzyme activity to 57% of control, 94% of which was in the active form. We conclude that, although all components for a reversible phosphorylative regulation of 3-hydroxy-3-methylglutaryl-CoA reductase activity are present in uterine epithelial cells, a role in the rapid changes in epithelial enzyme activity has not been demonstrated.

Animals↗