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M Loftus

Publications and source records attributed to M Loftus.

9 recordsLinked to original sources
PubMed2000

An analysis of atrophy in the medial mammillary nucleus following hippocampal and fornix lesions in humans and nonhuman primates.

Lesions of the hippocampal formation or transections of the fornix are followed by shrinkage of the medial mammillary nucleus (MMN). We determined whether the shrinkage of this nucleus was due to loss and/or shrinkage of neurons in addition to the loss of neuropil. We examined the MMN in a patient (KB) with an infarct that led to marked atrophy of the left hippocampus and subiculum, leaving the right MMN intact. Unbiased, stereological measurement techniques were used to compare the total cell number and individual neuronal cross-sectional areas in both left and right MMN in this patient and in two control human brains. We also analyzed the MMN in four macaque monkeys that underwent experimental unilateral transections of the fornix. The volume of the MMN on the lesioned side in KB was 55% of the unlesioned side (2.8 mm(3) vs 5.1 mm(3)); the MMN in the monkey cases were reduced to 47-58% of the volume of the nonlesioned side. Neurons in the deafferented MMN of KB and of the monkey subjects were decreased in cross-sectional area (16-20%, P < 0.0001). There was a trend toward decreased cell numbers (11-15%) on the lesioned side in all cases. We have estimated that the loss in cell number and shrinkage of remaining cells contribute negligibly to the 45% reduction in MMN volume. Therefore, the loss of neuropil (dendrites and afferent and efferent axons) appears to be the major contributor to the change in MMN volume.

Aged↗
PubMed1995

Expression of human inducible nitric oxide synthase in a tetrahydrobiopterin (H4B)-deficient cell line: H4B promotes assembly of enzyme subunits into an active dimer.

Murine inducible nitric oxide (NO) synthase (iNOS) is catalytically active only in dimeric form. Assembly of its purified subunits into a dimer requires H4B. To understand the structure-activity relationships of human iNOS, we constitutively expressed recombinant human iNOS in NIH 3T3 cells by using a retroviral vector. These cells are deficient in de novo H4B biosynthesis and the role of H4B in the expression and assembly of active iNOS in an intact cell system could be studied. In the absence of added H4B, NO synthesis by the cells was minimal, whereas cells grown with supplemental H4B or the H4B precursor sepiapterin generated NO (74.1 and 63.3 nmol of nitrite per 10(6) cells per 24 h, respectively). NO synthesis correlated with an increase in intracellular H4B but no increase in iNOS protein. Instead, an increased percentage of dimeric iNOS was observed, rising from 20% in cytosols from unsupplemented cells to 66% in H4B-supplemented cell cytosols. In all cases, only dimeric iNOS displayed catalytic activity. Cytosols prepared from H4B-deficient cells exhibited little iNOS activity but acquired activity during a 60- to 120-min incubation with H4B, reaching final activities of 60-72 pmol of citrulline per mg of protein per min. Reconstitution of cytosolic NO synthesis activity was associated with conversion of monomers into dimeric iNOS during the incubation. Thus, human iNOS subunits dimerize to form an active enzyme, and H4B plays a critical role in promoting dimerization in intact cells. This reveals a post-translational mechanism by which intracellular H4B can regulate iNOS expression.

3T3 Cells↗
PubMed1995

Subunit dissociation and unfolding of macrophage NO synthase: relationship between enzyme structure, prosthetic group binding, and catalytic function.

Macrophage NO synthase is a homodimer of 130 kDa subunits. Each subunit contains an oxygenase domain that binds iron protoporphyrin IX (heme) and tetrahydrobiopterin (H4biopterin) and a reductase domain that binds FAD, FMN, and calmodulin (CaM) [Ghosh & Stuehr (1995) Biochemistry 34, 801-807]. We have studied the dissociation and unfolding reactions of dimeric iNOS in urea to learn how enzyme structure relates to catalysis and prosthetic group binding. The iNOS dimer dissociated between 0 and 2.5 M urea, and the subunits partially unfolded at 2.5 M urea and above. Dimer dissociation was accompanied by loss of NO synthesis activity and release of bound H4biopterin from the protein. However, the dissociated subunits maintained their cytochrome c and ferricyanide reductase activities and retained near stoichiometric quantities of bound heme. The subunit unfolding transition was accompanied by loss of reductase activities and partial loss of bound heme but retention of bound flavins and CaM. The heme iron in the dissociated subunits remained coordinated through axial cysteine thiolate ligation. Kinetic analysis of dimer dissociation showed that loss of NO synthesis correlated with a loss of heme Soret absorbance at 398 nm and an appearance of absorbance bands at 377 and 460 nm, which were attributed to DTT coordination to the sixth position of the heme iron to form a mixed bisthiolate complex. Subunits could reassociate into a dimer when incubated with L-arginine and H4biopterin. Dimer formation correlated with proportional recoveries of NO synthesis and heme Soret absorbance at 398 nm. Thus, dimeric iNOS undergoes separate dissociation and unfolding transitions in urea, and each transition is accompanied by a loss of a specific catalytic function.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗
PubMed1988

Moving to change: action groups in an out-patient setting.

This paper presents an account of setting up and running an "Action Group" in an out-patient setting. The ideas and aims underlying "Action Groups" are presented through a contrast with Social Skills Training. The paper illustrates the way in which this "therapeutic philosophy" informs the details which are attended to in defining such a group's boundaries, procedure and purpose. A typical group session is described, and the paper seeks to illustrate how the therapeutic potency of such work is intimately related to the clarity of the group's boundaries and structure.

Adolescent↗
PubMedDate not supplied

DNA variants of alpha-1-antitrypsin in rheumatoid arthritis with and without pulmonary complications.

Restriction fragment length polymorphisms (RFLPs) of alpha-1-antitrypsin were studied in 99 subjects with rheumatoid arthritis alone, 21 subjects with rheumatoid arthritis and pulmonary fibrosis, 26 subjects with rheumatoid arthritis and bronchiectasis, and 86 controls. No associations with either rheumatoid arthritis itself or with the associated pulmonary disorders were noted in this U.K. Caucasoid population.

Alleles↗
PubMedDate not supplied

Critical times for families with a chronically ill child.

Parents identified difficult times in caring for their chronically ill children. A model describing these critical times was developed through an analysis of parent interviews. Predicting these critical times enables the health care team to optimize and maximize the effectiveness of their interventions.

Adolescent↗