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Biomedical subjects

A L Miller

Publications and source records attributed to A L Miller.

At least 91 records · Page 5Linked to original sources
PubMed1994

Immunological effects of acute and chronic nicotine administration in rats.

We previously demonstrated that acute nicotine administration decreased the response of rat blood leukocytes (PBL) to concanavalin A (ConA). We now extend those findings to a comparison between the effects of acute and prolonged nicotine exposure (ten daily injections), on PBL and splenocytes (SL). A single injection suppressed the PBL response to ConA and phytohemagglutinin (PHA); tolerance developed by ten injections. In contrast, acute nicotine did not affect SL response to ConA and reduced the PHA response only at the highest concentration. Ten nicotine injections enhanced SL responsiveness to PHA. The only change in PBL subsets was an increase in CD8+ cells following ten injections.

Animals↗
PubMed1993

Acute effects of neuroleptics on unmedicated schizophrenic patients and controls.

Acute administration of haloperidol (0.2 mg/kg) produced many more side effects in normal controls than in unmedicated schizophrenic patients. Prior to the neuroleptic challenge, both groups were on the peripheral monoamine oxidase inhibitor, debrisoquin, for at least 1 week, in order to enhance the relative contribution of CNS catecholamine metabolites to those measured in both plasma and urine. The patient group had higher plasma levels of methoxyhydroxyphenylglycol (MHPG) and homovanillic acid (HVA) and higher urinary MHPG output than controls, but there were no effects of haloperidol challenge, compared to placebo challenge. In both groups there were significant declines in plasma HVA levels from 8:30 AM to 12 NOON. These declines were unaffected by the haloperidol challenge. Explanations for the marked differences in behavioral effects of haloperidol on patients and controls include the possibility that dopamine receptor numbers were increased in the brains of the schizophrenic patients.

Adult↗
PubMed1993

Studies of catecholamine metabolism in schizophrenia/psychosis--I.

Acutely psychotic schizophrenic patients not taking antipsychotic medications and control subjects were studied before and during treatment with debrisoquin (DBQ), an inhibitor of monoamine oxidase, which does not penetrate into brain. Homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) were measured in plasma, urine, and cerebrospinal fluid (CSF). Significant differences between patients and control subjects were more easily discerned during treatment with DBQ. In patients, HVA was increased in plasma but not in urine or CSF, although MHPG was increased in all three fluids. There were many significant correlations between plasma MHPG and HVA levels and clinical ratings of psychoticism. Plasma MHPG correlated positively with both the severity of positive and negative symptoms and plasma HVA correlated only with positive symptom severity. These data suggest that both dopamine and norepinephrine (NE) metabolism are disturbed in acutely psychotic schizophrenic patients; disturbed NE metabolism may relate to negative symptoms as well.

Adult↗
PubMed1993

Studies of catecholamine metabolism in schizophrenia/psychosis--II.

Acutely psychotic schizophrenic patients were maintained on debrisoquin (DBQ) throughout 5 weeks of treatment with haloperidol. Treatment with haloperidol caused initial increases in urinary homovanillic acid (HVA) output that returned toward baseline by the 5th week. During haloperidol treatment, plasma levels of HVA tended to decrease, concurrent with increased renal clearance of HVA. Plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) levels and urinary MHPG output both decreased over the course of treatment. The differences in HVA and MHPG metabolism suggest differential effects of treatment on dopamine and norepinephrine systems. Neuroleptic treatment also abolished the marked morning decreases in plasma HVA concentrations (reported in part I).

Adult↗
PubMed1993

Light and heavy lysosomes: characterization of N-acetyl-beta-D-hexosaminidase isolated from normal and I-cell disease lymphoblasts.

We previously reported that I-cell disease lymphoblasts maintain normal or near-normal intracellular levels of lysosomal enzymes, even though N-acetylglucosamine-1-phosphotransferase activity is severely depressed or absent (Little et al., Biochem. J., 248, 151-159, 1987). The present study, employing subcellular fractionation on colloidal silica gradients, indicates that both light and heavy lysosomes isolated from I-cell disease and pseudo-Hurler polydystrophy lymphoblasts possess normal specific activity levels of N-acetyl-beta-D-hexosaminidase, alpha-D-mannosidase and beta-D-glucuronidase. These current findings are in contrast to those of cultured fibroblasts from the same patients, where decreased intralysosomal enzyme activities are found. Column chromatography on Ricinus communis revealed that N-acetyl-beta-D-hexosaminidase in both heavy and light I-cell disease lysosomal fractions from lymphoblasts possesses an increased number of accessible galactose residues (30-50%) as compared to the enzyme from the corresponding normal controls. Endo-beta-N-acetylglucosaminidase H treatment of N-acetyl-beta-D-hexosaminidase from the I-cell lysosomal fractions suggests that the majority of newly synthesized high-mannose-type oligosaccharide chains are modified to complex-type carbohydrates prior to being transported to lysosomes. This result from lymphoblasts differs from previous findings with fibroblasts, where N-acetyl-beta-D-hexosaminidase from I-cell disease and pseudo-Hurler polydystrophy lysosomes exhibited properties associated with predominantly high-mannose-type oligosaccharide chains.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Phosphorylation and subcellular location of alpha-L-fucosidase in lymphoid cells from patients with I-cell disease and pseudo-Hurler polydystrophy.

Mannose 6-phosphate is a recognition marker used by many newly made acid hydrolases for their transport to lysosomes. Previously, we investigated the incorporation of 32Pi into alpha-L-fucosidase of lymphoid cell lines from a healthy individual (control) and an I-cell disease patient [DiCioccio and Miller, Glycobiology, 1, 595-604 (1991)]. Phosphoserine was found in immunoprecipitable alpha-L-fucosidase of both control and I-cell lymphoid cells, but mannose 6-phosphate was identified only in enzyme of control cells. Extension of this investigation to lymphoid cultures of a pseudo-Hurler polydystrophy patient also identified only phosphoserine in alpha-L-fucosidase. Using [3H]mannose instead of 32Pi, the precise identification of mannose 6-phosphate in alpha-L-fucosidase of control cells, and its absence in alpha-L-fucosidase of I-cell and pseudo-Hurler cells, was established. The stoichiometry of phosphorylation of alpha-L-fucosidase in I-cell, pseudo-Hurler and control lymphoid cells was 3, 4 and 10 mol Pi/mol enzyme, respectively. alpha-L-Fucosidase was located in lysosomes isolated from control, I-cell and pseudo-Hurler lymphoid cells by subcellular fractionation on Percoll density gradients. Both I-cell and pseudo-Hurler lymphoid cells displayed normal intralysosomal activity of alpha-L-fucosidase despite lack of the mannose 6-phosphate marker. Thus, I-cell and pseudo-Hurler lymphoid cells must possess a mannose 6-phosphate-independent mechanism for directing alpha-L-fucosidase to lysosomes.(ABSTRACT TRUNCATED AT 250 WORDS)

Cells, Cultured↗
PubMed1993

Metabolic inhibition enhances Ca(2+)-activated K+ current in smooth muscle cells of rabbit portal vein.

The effect of metabolic inhibition on macroscopic and single-channel K+ currents in isolated rabbit portal vein myocytes was investigated by patch-clamp technique. Depression of adenosine triphosphate synthesis was produced by 2-deoxy-D-glucose (10 mM) and either cyanide (2 mM) or dinitrophenol (50 microM). Outward quasi-steady-state current evoked by a ramp protocol and outward time-dependent current during step depolarizations were increased during metabolic inhibition. The reversal potential for quasi-steady-state current shifted negatively toward equilibrium potential of K+ during treatment consistent with a role for K+ conductance and hyperpolarization of membrane potential. The macroscopic K+ current affected was 1) voltage dependent, 2) inhibited by intracellular Ca2+ chelation and low tetraethylammonium ion (1 mM) but unaffected by 4-aminopyridine (2 mM), and 3) associated with a rise in intracellular Ca2+ assessed by indo 1. Metabolic inhibition caused an increase in voltage-dependent large-conductance K+ channel (120-130 pS) activity in cell-attached patches of myocytes bathed in physiological solution (140 mM K+ in pipette). The channels were blocked in a flickery fashion by tetraethylammonium ion (0.5 mM) and inhibited with charybdotoxin (100 nM). We conclude that metabolic inhibition increases the activity of large-conductance Ca(2+)-activated K+ channels in vascular smooth muscle.

2,4-Dinitrophenol↗
PubMed1993

Calcium buffer injections inhibit cytokinesis in Xenopus eggs.

A slow cortical wave of high calcium accompanies the elongation of cleavage furrows in medaka fish eggs as well as in Xenopus eggs. We explored the role of such waves by injecting calcium buffers into Xenopus eggs at various times before and during first and second cleavage. Injection earlier than about 15 minutes before first cleavage normally starts delays it for hours. Injection between about 15 minutes and a few minutes before cleavage normally starts allows a (short) furrow to form on time but usually yields an eccentric one. This forms away from the injection side, often as far off-center as the egg's equator, and then regresses. Injection soon after it starts quickly arrests elongation of the furrow and eventually induces its regression; while injection a bit later likewise soon arrests elongation but allows delocalized furrow deepening to continue. The dependence of these inhibitory actions upon the dissociation constants and final cytosolic concentrations of the injected buffers indicates that they act as shuttle buffers to suppress needed zones of high calcium in the micromolar range. We conclude that the high calcium that is found within these furrows is needed to induce them, to extend them and even to maintain them. Moreover, while short, eccentric furrows often form as far off center as the equator, they somehow always form along a meridian through the animal pole. This seems difficult to explain by the orthodox, diastral model. Rather, it suggests that the cleavage furrows in Xenopus--and perhaps in animal cells quite generally--are directly induced by a diastema or telophase disc rather than by the asters.

Animals↗
PubMed1993

Self-other differentiation among psychotic and conduct-disordered adolescents as measured by human figure drawings.

24 psychotic-spectrum adolescents were compared with 23 conduct-disordered adolescents on a self-other drawing differentiation task. Of the 24 psychotic-spectrum disordered adolescents, 14 received the diagnosis of Psychotic Disorder NOS (Group 1) and the remaining 10 had diagnoses of Schizophrenia, Bipolar Disorder with Psychotic Features, and Schizoaffective Disorder (Group 2). Interestingly, less impaired adolescents (Groups 1 and 3, the conduct-disordered group) showed significantly more difficulty than the more impaired adolescents (Group 2) on self-other differentiation as measured by their differentiated drawings.

Adolescent↗
PubMed1993

Animistic thinking in psychotic versus conduct-disordered hospitalized adolescents.

25 adolescents showing a Psychotic-spectrum Disorder were compared with 24 adolescents showing Conduct Disorder on a task eliciting reasons for attributing life to an ambiguous pictorial stimulus (dough on a beach). Consistent with expectations from earlier research, the psychotic adolescents showed greater modes of animistic thinking (attributions of life to nonlife forms) than conduct-disordered youth, associated with theorized merging between self and the nonhuman environment. Implications are discussed.

Adolescent↗
PubMed1992

Binding receptors for alpha-L-fucosidase in human B-lymphoid cell lines.

An established mechanism for directing newly made acid hydrolases to lysosomes involves acquisition of mannose 6-phosphate residues by the carbohydrate portion of acid hydrolases followed by binding to specific membrane-bound transport receptors and delivery to lysosomes. Two distinct phosphomannosyl receptors (CI-MPR and CD-MPR) have been identified. Alternative mechanisms for trafficking acid hydrolases exist. This report examines means for the possible receptor-mediated intracellular transport of alpha-L- fucosidase in lymphoid cells. The binding of alpha-L-fucosidase to intact cells and to total cell membrane preparations, in conjunction with immunoassays of solubilized membrane preparations, revealed the presence of CI-MPR and CD-MPR on human lymphoid and fibroblast cell lines. The mean level of CD-MPR in nine lymphoid cell lines was 7.2-fold greater than CI-MPR. The mean level of CI-MPR in two fibroblast lines was 3.8-fold greater than CD-MPR. The mean content of CI-MPR was 19.5-fold greater in the fibroblasts than in the lymphoid cells. The CD-MPR content of fibroblasts and lymphoid cells was nearly equivalent. Among these cell lines were a fibroblast and a lymphoid line from the same individual. These results indicate that human B-lymphoid cells are deficient in CI-MPR and suggest that modulation of expression of CI-MPR and CD-MPR in lymphoid cells differs from that in fibroblasts, including cell lines with identical genomes. No specific receptor capable of binding alpha-L-fucosidase independent of mannose 6-phosphate was demonstrable, despite published results that support the existence of a mannose 6-phosphate independent trafficking mechanism in lymphoid cells for this enzyme.

B-Lymphocytes↗
PubMed1992

Purification and characterization of human lymphoblast N-acetylglucosamine-1-phosphotransferase.

N-Acetylglucosamine-1-phosphotransferase (GlcNAcPTase) was solubilized with 2% Tergitol NP-10 from cultured human lymphoblast cells and purified 3840-fold with 14% recovery using lentil lectin-Sepharose 4B, DEAE-Sephacel and Sephacryl S-400 chromatographies. The partially purified enzyme requires the non-ionic detergent Tergitol NP-10 and a divalent cation, Mn2+ or Mg2+, for its activity and exhibits an optimal pH at 7.2-7.5 in Tris-maleate buffer. Kinetic studies demonstrated an apparent Km of 24 microM for the donor UDP-N-acetylglucosamine and of 117 mM for the artificial acceptor alpha-methylmannoside. The GlcNAcPTase is inhibited by UDP and UDP-glucose, and by negatively charged phospholipids including phosphatidylserine, phosphatidylglycerol and phosphatidic acid. The apparent mol. wt of the human lymphoblast GlcNAcPTase is approximately 1000 kDa, which is analogous to that reported for the partially purified enzyme from rat liver (Waheed et al., 1982).

Chromatography, Affinity↗
PubMed1992

Changes in aldose reductase after crush injury of normal rat sciatic nerve.

The response of aldose reductase (AR) to crush injury was studied in normal rat sciatic nerve. Enzyme activity and immunoreactivity of AR were determined at intervals of 1, 5, 14, 28, and 35 days after crush and correlated with histologic and immunocytochemical observations. During nerve degeneration in the distal segments of crushed nerves, a significant reduction in AR activity was detected. At 5 and 14 days, coincident with Schwann cell proliferation, enzyme activity decreased by nearly two- and fourfold, respectively. Although activity of AR increased by 28 days during nerve regeneration, it was not restored to normal levels at 35 days. Similar reductions were observed with the immunoblotting of the enzyme. Quantitative analysis of immunogold labelling on electron micrographs confirmed that proliferating as well as remyelinating Schwann cells contained reduced gold particle density compared to Schwann cells of noncrushed myelinated fibers. Immunoblots of P0, a marker for the degree of Schwann cell differentiation or myelination, showed that the temporal sequence of changes in P0 paralleled that of AR. Thus expression of AR is a function of differentiated or mature Schwann cells. The putative volume regulatory role of AR in Schwann cells may become superfluous during Wallerian degeneration.

Albumins↗