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Biomedical subjects

I MacDonald

Publications and source records attributed to I MacDonald.

At least 19 recordsLinked to original sources
PubMed1998

Time of day effects in, and the relationship between, sleep quality and movement.

The study aimed to measure the effects of a 27-h 'day' sleep-wake regime on actigraphic and subjective sleep variables, and to examine the relationships between these variables. Nine subjects spent 30 days and nights in the laboratory. After sleeping 8 h for each of 8 nights, the subjects had an imposed 27-h 'day', for 18 'days', remaining in bed for 9 h on each sleep period. Sleep periods therefore started 3 h later each day, although subjects' circadian rhythms stayed entrained to 24 h, because subjects were not isolated from the natural light-dark cycle. Time asleep, subjective sleep efficiency and subjective sleep quality, but not movement during sleep, were found to be significantly affected by time of going to bed. There were significant decreases in movement during recovery sleeps following each of two episodes of 26 h sleep deprivation. Over the study there were significant within-subject correlations between subjective sleep quality and subjective sleep efficiency (rav = 0.65), movement during sleep and subjective sleep efficiency (rav = -0.48), and movement during sleep and subjective sleep quality (rav = -0.26). We conclude that sleep movement, despite its low within- and between-subjects variability, is nevertheless a statistically reliable, but weak, indicator of subjective sleep efficiency and quality.

Adult↗
PubMed1997

Effects on Accidents of Time into Shift and of Short Breaks between Shifts.

This study aimed to determine whether there was a peak in accidents in the second to fourth hours within a shift and to compare the effect on accidents of the presence or absence of a break of only eight hours between shifts in a shift cycle ("quick returns"). Archival accident records were obtained for a four-year period from two sister works within the same division of a heavy-industrial organization. The works had many similarities but differed in the shift systems used. One had "quick returns," whereas the other did not. Accident frequencies were analyzed across four variables, site, shift, time on shift, and process code (process code identified the process area in which the worker operated). These were analyzed by hierarchical log-linear analysis, using a significance level of 0.05. The results indicated there was a peak in accidents in the second and third hours into a shift, but provided only slight evidence for a detrimental effect of "quick returns."

Journal Article↗
PubMed1996

Transforming growth factor-beta 1 cooperates with anti-immunoglobulin for the induction of apoptosis in group I (biopsy-like) Burkitt lymphoma cell lines.

Group I Burkitt lymphoma (BL) cell lines, which retain the original biopsy phenotype, have been shown to enter apoptosis in response to a number of external stimuli including serum deprivation, thermal shock, addition of calcium ionophore, and ligation of surface immunoglobulin (Ig) by antibody. Transforming growth factor-beta 1 (TGF beta 1) is known to cause growth arrest in BL lines. Here we show that while it is by itself capable of promoting some degree of apoptosis in group IBL cells, TGF beta 1 cooperates with anti-immunoglobulin to this end. Trimeric soluble recombinant human CD40 ligand (sCD40L) was able to inhibit apoptosis induced by the combination of agonists to some degree, but such rescue proved to be short-lived. Both TGF beta 1 and anti-Ig individually caused BL cells to undergo growth arrest at the G1 phase of cell cycle before their entry into apoptosis: the consequence of sCD40L addition was to maintain the cells in cycle for longer. No induction of the apoptosis-protecting gene, bcl-2, occurred in the presence of sCD40L. These findings are discussed, particularly highlighting the relationship existing between survival and the cell cycle. The strong cooperative effects observed between anti-Ig and TGF beta 1 in promoting apoptosis and the inability of CD40 to signal for long-term rescue raise the potential for a novel therapeutic attack on B-cell lymphoma.

Animals↗
PubMed1996

The difference between activity when in bed and out of bed. II. Subjects on 27-hour "days".

Nine healthy subjects have been studied while exposed to the normal alternation of light and dark, but with their sleep and activity pattern adjusted to a 27-h "day" for 17 imposed "days." Rectal temperature showed clearly the competing influences of 27-h and 24-h components, and these were separated by the method of "purification." The method indicated that the endogenous component had a constant amplitude throughout the experiment and remained entrained to solar (24-h) time; by contrast, the exogenous component followed the imposed 27-h "day" and increased rectal temperature in proportion to the amount of subjects' activity. Wrist movement was used to assess activity while in bed (attempting sleep) and out of bed (when naps were forbidden). While these results confirmed adherence of the subjects to the imposed 27-h "days," they also showed that the dichotomy between "out of bed" activity and "in bed" inactivity depended on the phase relationship between endogenous (24h) and exogenous (27h) components. Thus, the dichotomy was highest and was equal to that during control days (with a conventional 24-h life-style) when the two components were in phase and lowest when the solar and imposed day were in antiphase. This was due to changes in activity, both during time spent in bed and out of bed. We confirm that this protocol can produce valuable information about the properties of the circadian system in humans and the value of the process of purification of temperature data. We have established also that the very simple and noninvasive measurement of wrist movement, coupled with its use to calculate dichotomy indices, provides valuable information that both confirms and extends the results obtained from the more conventional (but also more invasive) measurement of rectal temperature.

Bed Rest↗
PubMed1995

Engagement of CD20 suppresses apoptosis in germinal center B cells.

In a screen of 67 monoclonal antibodies (mAb) included in the Blind Panel of B cell antibodies for the 5th International Workshop on Human Leukocyte Differentiation Antigens, only the CD20 mAb--included as a positive control for immunophenotyping studies--was found to suppress the spontaneous apoptosis which occurs in human germinal center (GC) B cells when placed in tissue culture at 37 degrees C. Further detailed study using the 1F5 mAb confirmed this observation, showing that rescue from apoptosis via CD20, while not as efficient as that obtained on ligating CD40, was of similar magnitude to that achieved on engagement of surface immunoglobulin (sIg) by immobilized antibody. Also similar to anti-Ig, the CD20 mAb rescued from apoptosis without priming for the proliferation of GC B cells: this was quite different to its action on resting, non-GC B cells, where it provides a potent priming signal for cell cycle progression in response to IL-4 or anti-CD40. Unlike the survival signal engendered via sIg, CD20 engagement neither mobilized Ca2+ from intracellular stores or opening of a Ca2+ channel with 1F5, nor did it affect the ability of anti-Ig to open a Ca2+ gate in GC B cells. An unexpected feature of CD20-mediated rescue of GC B cells from apoptosis was a failure to turn on Bcl-2 expression.

Antibodies, Monoclonal↗
PubMed1994

Stimulation of human B lymphocytes by phorbol esters reported to be selective in the protein kinase C isoforms they activate.

It is reported here that B cells can be stimulated by two phorbol esters which, in cell free substrate phosphorylation assays, are selective in the PKC isoforms they activate: thymeleatoxin (Thy) stimulates all of the classical (c) or Group A PKCs (alpha, beta 1, beta 2 and gamma) but not PKC delta and epsilon which belong to the novel (n) or Group B PKCs, while 12-deoxyphorbol-13-O-phenylacetate-20-acetate (dPPA) is a specific activator of PKC beta 1. By itself, phorbol 12-myristate, 13-acetate (PMA)--which activates all cPKC and nPKC--was, on a molar basis, some 40-times more potent than either Thy or dPPA which were themselves equipotent at promoting DNA synthesis in resting B cells: the peak response achieved with Thy and dPPA was higher (1.4 x) than that obtained with PMA. In the presence of calcium ionophore, PMA, Thy and dPPA all stimulated a higher (and equivalent) peak response which was achieved at a lower phorbol ester concentration in each case: however, whereas Thy now approached PMA in potency, dPPA remained some 40-times less potent.

B-Lymphocytes↗
PubMed1994

Insulin sensitivity in post-obese women.

1. Both increased and decreased sensitivity to insulin has been proposed to precede the development of obesity. Therefore, insulin sensitivity was measured during a 2 h hyperinsulinaemia (100 m-units min-1 m-2) euglycaemic (4.5 mmol/l) glucose clamp combined with indirect calorimetry in nine weight-stable post-obese women and in nine matched control women preceded by 12 h fasting after 48 h on a standardized diet. 2. Both glucose disposal rate (post-obese women, 9.5 +/- 2.2 mg min-1 kg-1, control women, 11.2 +/- 1.4 mg min-1 kg-1, not significant) and glucose oxidation (3.6 +/- 0.5 mg min-1 kg-1 versus 4.0 +/- 0.7 mg min-1 kg-1, not significant) were similar in the two groups during the last 30 min of the clamp. Lipid oxidation also decreased similarly during the clamp in the post-obese women (from 30.4 +/- 12 to 2.0 +/- 7 J min-1 kg-1) and in the control women (from 33.6 +/- 11 to 5.4 +/- 8 J min-1 kg-1, not significant). Basal plasma concentrations of free fatty acids were similar, but at the end of the clamp free fatty acids were lower in the post-obese women than in the control women (139 +/- 19 and 276 +/- 48 mumol/l, P = 0.02). 3. We conclude that the insulin sensitivity of glucose metabolism is unaltered in the post-obese state. The study, however, points to an increased antilipolytic insulin action in post-obese subjects, which may favour fat storage and lower lipid oxidation rate postprandially.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Central role of CD40 and its ligand in B lymphocyte responses to T-dependent antigens.

In order to mount an effective antibody response to soluble and certain other types of antigens, B cells need help from T cells. Recently, an important receptor-ligand pair has been identified as essential for successful cognate interaction between these two classes of lymphocytes. CD40 was first identified as a receptor-like molecule on B cells which when ligated by antibody could deliver signals to prime for growth, differentiation, or survival. Later its counterstructure--termed CD40 ligand (CD40L)--was discovered to be an inducible type II glycoprotein of helper T cells. In this review, the central role of the CD40-CD40L interaction in the various phases of the B cell response to T-dependent antigens is discussed drawing from both in vitro and in vivo studies.

Animals↗
PubMed1993

Decrease in the size of the myotonic dystrophy CTG repeat during transmission from parent to child: implications for genetic counselling and genetic anticipation.

Recently an unstable trinucleotide CTG repeat, located within the 3' untranslated region of a gene on 19q13.3 was discovered in kindreds with myotonic dystrophy (DM). The age-of-onset/severity of DM shows a good correlation with CTG repeat size, and pedigrees and data reported to date have shown a striking trend toward amplification of the size of the CTG repeat during transmission from parent to child. The amplification has been accepted as the biological explanation for anticipation in the clinical severity observed in many families with DM. In this paper we report on 3 families where CTG amplification decreased during transmission from parent to child. In one case there was a gene conversion event, while in the remaining 2 there was a simpler reduction in the size of the repeat length. The changes appear to have been accompanied by a reduction in clinical severity in the child when compared to the parent. These observations are discussed in terms of their clinical implications and the biases that may exist in much of the reported data.

Adolescent↗
PubMed1992

Leber's hereditary optic neuropathy: a model for mitochondrial neurodegenerative diseases.

A number of human diseases have been attributed to defects in oxidative phosphorylation (OXPHOS) resulting from mutations in the mitochondrial DNA (mtDNA). One such disease is Leber's hereditary optic neuropathy (LHON), a neurodegenerative disease of young adults that results in blindness due to atrophy of the optic nerve. The etiology of LHON is genetically heterogeneous and in some cases multifactorial. Eleven mtDNA mutations have been associated with LHON, all of which are missense mutations in the subunit genes for the subunits of the electron transport chain complexes I, III, and IV. Molecular, biochemical, and population genetic studies have categorized these mutations as high risk (class I), low risk (class II), or intermediate risk (class I/II). Class I mutations appear to be primary genetic causes of LHON, while class II mutations are frequently found associated with class I genotypes and may serve as exacerbating genetic factors. Different LHON pedigrees can harbor different combinations of class I, II, or I/II mtDNA mutations, as shown by the complete sequence analysis of the mtDNAs of four LHON probands. The various mtDNA genotypes included an isolated class I mutation, combined class I+II mutations, and combined class I/II+II mutations. The occurrence of such genotypes supports the hypothesis that LHON may result from the additive effects of various genetic and environmental insults to OXPHOS, each of which increases the probability of blindness.

Adolescent↗
PubMed1990

Apparent Smith-Lemli-Opitz syndrome in a child with a previously undescribed form of mucolipidosis not involving the neurons.

A diagnosis of Smith-Lemli-Opitz syndrome was made shortly after birth in a small-for-dates infant, on the basis of a characteristic face, penoscrotal hypospadias, bilateral postaxial hexadactyly, and bilateral syndactyly of toes 2-3. The clinical course was marked by failure to thrive, severe delay, refractory myoclonic jerks beginning at age 2 months, and increasing hepatosplenomegaly. He developed corneal clouding and increased gingival hypertrophy and died at age 18 weeks. Autopsy disclosed widespread storage of mucopolysaccharides and lipids within the macrophages and, to a lesser extent, parenchymal cells, of all organ systems. There was extensive demyelination of the cerebral white matter, and dystrophic calcification in the cerebrum, cerebellum, and brainstem. There was no evidence of primary neuronal involvement in the storage. Although the chance concurrence of 2 uncommon diseases is rare, a causal link between the clinical anomalies and the storage disorder cannot be argued convincingly on the basis of one case. Careful pathologic studies of other children who die with clinical signs compatible with Smith-Lemli-Opitz syndrome are indicated.

Brain↗
PubMed1989

Use of the polymerase chain reaction for the differential cross screening of libraries cloned into phage-lambda-based vectors.

We describe a simple and rapid method that can be used to identify sequences present in any two DNA libraries (either genomic or cDNA), provided only that the libraries are in different vectors with different cloning sites. This procedure makes use of the polymerase chain reaction (PCR) to amplify the inserts of one library. The product of the PCR reaction is then used to screen a second library to identify sequences which are common to both. We illustrate the use of this method for the systematic isolation of human X-chromosome-linked genomic clones that harbor sequences expressed in human chorioretinal tissue.

Animals↗
PubMed1988

In situ detection of rubella RNA and antigens in cultured cells.

We developed in situ hybridization and immunofluorescent procedures to detect rubella RNA and antigens in tissue-cultured cells infected with rubella virus. cDNA fragments of the rubella virus E1 structural gene were used as probes for in situ hybridization to detect rubella RNA sequences in Vero cells infected with rubella virus. Using antibodies against rubella proteins, indirect immunofluorescence detected rubella virus structural proteins in Vero cells infected with rubella virus. The immunofluorescence method has also been applied to study the expression of rubella polypeptide E1 in transfected COS cells and may be applied to the detection and study of persistent rubella virus infection in human tissues.

Animals↗
PubMed1988

Recurrent and residual renal calculi in children.

One hundred and thirteen children with non-metabolic urinary tract calculi were operated on between 1960 and 1983. One hundred were followed up for 3 to 17 years (mean 8.2). Seventeen children (15%) developed recurrent calculi after complete clearance at the initial operation and in 13 of these the stones recurred within 5 years. Proteus urinary infection was a constant feature of stone recurrence. Five patients required re-operation for removal of the recurrent calculus. Small residual caliceal fragments were left behind in 17 children but only 3 required surgical removal.

Adolescent↗