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Biomedical subjects

R Miller

Publications and source records attributed to R Miller.

At least 631 records · Page 35Linked to original sources
PubMed1988

Complete trisomy 17p a relatively new syndrome.

A patient with a de novo duplication of 17p is described. A comparison with five other published cases indicates several features in common that seem characteristic of the syndrome. Primary features include, low birth weight, small size, severe mental and motor retardation, heart defect, failure to thrive and peculiar facial traits. The prominent facial features are, a tendency for round and flat mid face, small palpebral fissures, hypertelorism, microcephaly and low set prominent ears.

Abnormalities, Multiple↗
PubMed1988

Distribution of the 124-kd antigen defined by monoclonal antibody AML-1-99 on normal and leukemic myeloid cells.

We have produced a monoclonal antibody (MoAb), AML-1-99, that defines a novel 124-kd protein antigen expressed on a subpopulation of monocytes and on the majority of hematopoietic progenitor cells of the granulocyte-monocyte (CFU-GM), erythroid, and mixed-lineage classes. AML-1-99 is lytic to bone marrow (BM)- and peripheral blood-derived progenitor cells in the presence of rabbit complement (C'). AML-1-99 is not toxic to progenitor cells in the absence of C', nor does it modify their growth when included in colony-forming cultures. Several leukemia cell lines, including HL-60, U937, KG-1a, and Daudi cells, express the antigen on the majority of cells. Freshly isolated leukemia cells from patients with acute myelogenous leukemia (AML) react variably with AML-1-99. Leukemia colony-forming cells from several AML patients express the antigen and could be eliminated by treatment with AML-1-99 and C'. Cell sorting and immune rosette techniques were successfully applied to normal BM and chronic myelocytic leukemia cell populations using AML-1-99 with the result that significant enrichment of CFU-GM could be accomplished. The pattern of reactivity of this MoAb and its apparent molecular weight suggests that AML-1-99 recognizes a newly defined myeloid-associated cell surface antigen.

Antibodies, Monoclonal↗
PubMed1987

Population pharmacokinetics of phenytoin in South African black patients.

In the routine care of 37 patients at the epilepsy outpatient clinic of Baragwanath Hospital, Johannesburg, 100 steady-state serum phenytoin concentrations were measured. Total and free phenytoin as well as albumin serum concentrations were determined. Computer analysed data were fitted to the Michaelis-Menten model for steady-state serum concentrations. As a function of the Michaelis-Menten constant (P less than 0.1) total serum phenytoin concentration provided a significantly better fit than free phenytoin combined with albumin serum concentrations. The Vm and Km of 6.5 mg/kg/d and 13.6 mumol/l respectively, determined by using total serum concentration, could be to estimate phenytoin dosage requirements in a hospital population.

Adolescent↗
PubMed1987

Novel technique for isolation of human lung mast cells.

A novel technique for isolation of human lung mast cells is developed. Human lung tissue was enzymatically digested and the cells were partially purified by centrifugation on Percoll density gradient. Cells obtained at the Percoll density of 1.05-1.09 g/ml were then subjected to a cell sorter equipped with a single argon laser beam (FACS 440). Using four criteria as density, granularity, size and autofluorescence, four major cell populations were identified. One of the major populations contained 70-95% mast cells with a mean and SE values of 88 +/- 11% purity, n = 18 as determined by the measurement of total histamine content, light microscopic observation of stained cells with toluidine blue and estrase, and surface-stained IgE fluorescence antibody. Approximately less than 10% mast cells were identified in the three other major cell populations. Mast cells isolated by FACS were found to be intact, viable (approximately equal to 90%) and functionally normal as determined by the release of histamine evoked after stimulation with ionophone A23187, or challenged with anti-human IgE.

Cell Separation↗
PubMed1987

A nuclear specific glycoprotein representative of a unique pattern of glycosylation.

Whole rat liver nuclei were reacted with UDP-[14C]galactose in the presence of bovine beta(1----4) galactosyltransferase. The reaction mixture was electrophoresed on a reducing sodium dodecyl sulfate-polyacrylamide gel. Autoradiograms of the gel demonstrated a major labeled broad band migrating with an apparent molecular weight of 65,000-66,000. A number of other less prominently labeled bands were also present. The labeled 65,000-66,000 band when cut from the gel and subjected to alkaline reduction while in the gel matrix exclusively yielded a 14C-labeled disaccharide that co-migrated with a [14C]Gal-GlcNAcol standard in descending paper chromatography. Treatment of this disaccharide with beta-galactosidase (beta-D-galactoside galactohydrolase; EC 3.2.1.23) from Aspergillus niger removed all the [14C]galactose label. Treatment of the labeled 65,000-66,000 polypeptide with Endoglycosidase F, however, did not remove the [14C]galactose label. Western transfer blots of sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels performed with horseradish peroxidase-labeled succinyl wheat germ agglutinin, a lectin specific for GlcNAc, on unlabeled nuclei revealed a dominant band at 63,000-64,000. Subjecting 14C-labeled nuclei to this procedure resulted in a shift of the major horseradish peroxidase-labeled succinyl wheat germ agglutinin band to 65,000-66,000. The shifted band was coincident with the [14C]galactose band as visualized on an autoradiogram. A survey of other rat tissue nuclei revealed the same spectrum of [14C]galactose acceptor proteins with a dominant 65,000-66,000 galactose-labeled band.

Animals↗
PubMed1987

Therapeutic drug level monitoring in the management of epilepsy.

A selected group of poorly controlled epileptic patients had their drug plasma concentrations measured. Of those on a single drug, 33% were noncompliant, 33% had drug concentrations in the subtherapeutic or toxic ranges and 34% had levels in the therapeutic range, 86% of which were in the low therapeutic range. In only 9% of the group on multiple drugs were both drug levels in the therapeutic range. Twenty-two per cent of patients were non-compliant for both drugs. Patients were followed up over 12 months with drug level monitoring and dosage adjustments; 49% were seizure-free and 36% had a reduction in seizure frequency of at least 50% over an 8-month period. All but 3.9% were put on a single-drug regimen, and 15.6%, which matched well with the number of non-compliant patients, had no change in seizure frequency. Therapeutic drug level monitoring is a most useful aid in rationalising drug therapy and improving seizure control.

Adolescent↗
PubMed1987

Anorectal temperature sensation: a comparison of normal and incontinent patients.

In the skin, temperature sensation plays an important role in discriminating between gas, liquid and solid. To elucidate the role of temperature sensation in idiopathic faecal incontinence we studied the minimum detectable temperature change in the lower, middle and upper zones of the anal canal and rectum in 33 normal subjects, and 20 patients with idiopathic faecal incontinence. A water perfused thermode was used to vary anorectal temperature from 37 degrees C down to 32.5 degrees C and up to 41.5 degrees C. The temperature change was reported by the patient as the thermode temperature varied from 37 degrees C to each extreme and on return to base line. The anal canal in the control group was highly sensitive to temperature change, the lower rectum was significantly less sensitive (P less than 0.0001). At each level in the anal canal and lower rectum the incontinent group were significantly less sensitive than their controls (P less than 0.005). The mid-rectum had no appreciable sensation in either group. We consider that this sensory deficit may be an important factor in idiopathic faecal incontinence.

Adult↗
PubMed1987

The time course of neuroleptic therapy for psychosis: role of learning processes and implications for concepts of psychotic illness.

In neuroleptic therapy for psychotic illness, clinical improvement is produced more slowly than is central dopamine blockade, and its time course is highly variable between patients. A theory of neuroleptic-responsive psychotic illness thus requires more than dopamine blockade, though that appears to be the first step in the therapeutic process. Some previous explanations given for the protracted time course of neuroleptic therapy are discussed, with emphasis on the hypothesis of delayed inactivation of midbrain dopamine neurones. For various reasons all explanations are unsatisfactory. An alternative hypothesis is proposed in which neuroleptic-responsive psychoses are seen as arising from a hyperactivity of the associations of thought. Such psychoses thus involve a disorder of a high-level learning process, namely the elaboration of memories of thoughts and beliefs. Neuroleptic drugs are envisaged to remedy this process, but not to eradicate the abnormal memories already formed. Psychotic symptoms may thus outlast the start of neuroleptic therapy by many weeks. It is suggested that the pharmacological characteristics of the hypothetical learning process involved in generating psychotic symptoms are analogous to those of a simpler learning process, defineable in animal experiments - namely, the reward component in instrumental conditioning. A preliminary case is made that the relative potency of different neuroleptic drugs in antipsychotic therapy can better be predicted by their relative potency in retarding such a variety of learning, than by other behavioural tests of these drugs.

Antipsychotic Agents↗
PubMed1987

Cell density-dependent vitamin D effects on calcium accumulation in rat osteogenic sarcoma cells (ROS 17/2).

Rat osteogenic sarcoma cells have been used widely as a model system to study actions of 1,25(OH)2D3 and other hormones in osteoblastlike cells. However, some of the pleiotypic manifestations of hormones in these cells vary greatly dependent upon the cell population density and other conditions of culture. Therefore, we have studied the effect of cell density on the relationship between 1,25(OH)2D3 and the initial 45Ca accumulation in ROS 17/2 cells in order to establish conditions suitable for studying the effect of 1,25(OH)2D3 on calcium fluxes in these cells. Cells were grown in the presence and absence of 1,25(OH)2D3 for 48 hours and then incubated for 4 min in the culture medium containing 0.5 microCi/ml of 45CaCl2. In high population density cultures, 0.25-1.0 pg/ml of 1,25(OH)2D3 stimulated the intracellular accumulation of 45Ca (cpm/mg protein), whereas 80 pg/ml or higher concentrations inhibited accumulation of 45Ca. In low density cultures, concentrations less than 80 pg/ml had no effect, 80-120 pg/ml increased the intracellular accumulation, and as much as 200 pg/ml failed to show the inhibitory effect. These results indicate that the ROS 17/2 cell responses to 1,25(OH)2D3 are biphasic--low concentrations stimulating and high concentrations inhibiting 45Ca accumulation. The sensitivity of the cells to 1,25(OH)2D3 increases as the cell population density increases. These observations suggest that the culture density and dose-response relationship must be carefully defined in in vitro studies utilizing osteogenic cell culture systems.

Animals↗
PubMed1987

Early manifestations of vitamin D effects in rat osteogenic sarcoma cells.

We have recently demonstrated that 48 hour exposure of ROS 17/2 cells to low concentrations of 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) (1.0 pg/ml) stimulated the cellular accumulation of 45Ca, and exposure to high concentrations (160 pg/ml) inhibited such accumulation. In the present study, short-term (15 min) effects of the sterol on 45Ca accumulation in ROS 17/2 cells were compared with the long-term (48 hours) effects in order to clarify mechanisms responsible for 1,25(OH)2D3 control of calcium metabolisms in ROS 17/2 cells. ROS 17/2 cells were grown for 48 hours in the presence and absence of 1,25(OH)2D3 and then incubated for an additional 15 min in the presence and absence of 1,25(OH)2D3 immediately before measuring 45Ca accumulation. Cellular 45Ca was measured after incubating the cells in the medium containing 0.5 microCi/ml of 45CaCl2 for 4 min at 25 degrees C. The effect of actinomycin D was determined by preincubating the cells in 0.1 microgram/ml of actinomycin D for 45 min at 25 degrees C. Exposure to low concentrations (1.0 pg/ml) of 1,25(OH)2D3 for either 48 hours or 15 min increased 45Ca in the cells by 10-20%. An additional 15 min exposure following 48 hour exposure yielded an increase in the cellular 45Ca similar to that after 48 hours or 15 min exposure. Exposure to high concentrations (160 pg/ml) for either 48 hour or 15 min decreased cell 45Ca by approximately 20%. An additional 15 min exposure to the high concentrations did not change the 48 hour effect. Actinomycin D reversed early inhibitory effects of high concentrations, but had no effect on the early stimulatory effects of low concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Requirement for mitogen, T cell-accessory cell contact, and interleukin 1 in the induction of resting T-cell proliferation.

The role of interleukin 1 (IL-1) and accessory cells (AC) in mitogen-driven, resting human peripheral blood T lymphocyte proliferation was examined utilizing highly purified T-cell preparations. Such preparations fail to respond to optimal concentrations of the lectin phytohemagglutin (PHA) or interleukin 2 (IL-2), indicating the functional depletion of monocytes (Mo.) and of activated T cells, respectively. The requirement for Mo. and IL-1 was quantitatively determined by adding known loads of Mo. and of recombinant human IL-1 alpha or beta forms (r-hIL-1, alpha/beta) to T-cell preparations and monitoring the resultant proliferative responses to the mitogens PHA, concanavalin A (Con A), the anti-CD3 monoclonal antibody (mAb) Leu 4, and Sepharose beads-linked Leu 4. Although some mitogens induced IL-2r gene transcription and surface expression in T cells, all mitogens tested failed to drive T cells to proliferate in the absence of Mo. r-h IL-1, as well as Mo.-conditioned media, failed to support the proliferation of mitogen-treated T cells. However, r-h IL-1 significantly amplified the proliferative responses of mitogen-treated T cells when suboptimal loads of Mo. were added. Both r-h IL-1 alpha and beta forms behaved identically in all the aforementioned experiments. The necessity of T cell-Mo. contact for T-cell proliferation was established by demonstrating that T cells separated from Mo. by a semipermeable membrane which allowed free diffusion macromolecules failed to proliferate to the mitogens tested. In contrast to lectins and anti-CD3 mAb phorbol-12-myristate-13-acetate (PMA) induced on its own a modest proliferative response which was greatly enhanced by r-h IL-1 independent of the addition of monocytes. The mechanism of r-h IL-1 action in supporting PMA-primed, T-cell proliferation involved the induction of IL-2 synthesis. We conclude that IL-1 does not substitute for the need for Mo. in supporting mitogen-driven T-cell proliferation. Mitogens, direct accessory-T-cell contact, and IL-1 each act, in this order, to bring about resting T-cell proliferation. The distinct behavior of PMA might relate to its ability to substitute for monocyte contact in promoting the progress of T cells through the cell cycle.

Antigen-Presenting Cells↗