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Biomedical subjects

J R Baker

Publications and source records attributed to J R Baker.

At least 163 records · Page 9Linked to original sources
PubMed1991

Long-term improvement of hypercholesterolemia after ex vivo gene therapy in LDLR-deficient rabbits.

Familial hypercholesterolemia (FH) is an inherited disorder in humans that is caused by a deficiency of low density lipoprotein receptors (LDLRs). An animal model for FH, the Watanabe Heritable Hyperlipidemic rabbit, was used to develop an approach for liver-directed gene therapy based on transplantation of autologous hepatocytes that were genetically corrected ex vivo with recombinant retroviruses. Animals transplanted with LDLR-transduced autologous hepatocytes demonstrated a 30 to 50 percent decrease in total serum cholesterol that persisted for the duration of the experiment (122 days). Recombinant-derived LDLR RNA was harvested from tissues with no diminution for up to 6.5 months after transplantation.

Animals↗
PubMed1991

Significance of variation in turnover of glycated albumin on indices of diabetic control.

We measured the half-time of disappearance of 125I-labelled glycated albumins in a rat model of diabetes with continuous infusion of physiological saline and insulin. Our results indicate that (i) in non-diabetic rats, continuous infusion of saline per se did not affect the concentrations of glucose or of fructosamine, and the half-time of disappearance of albumin was unaffected by degree of glycation; (ii) hyperglycaemia (mean plasma glucose concentration of 18-27 mmol/l) caused a small but significant increase in half-time of labelled glycated albumin disappearance from a mean of 42 h to a mean of 47 h; (iii) this effect of hyperglycaemia outweighed any effect of increase in albumin excretion detected in poorly controlled diabetic rats without infusion. We conclude that the effect of hyperglycaemia in slowing turnover of glycated albumin is likely to be insignificant in relation to its effect in promoting glycation, and may be species-dependent. However, in nondiabetics, variation of turnover of glycated albumin may well be significant in explaining the wide interindividual variation in concentration of glycated protein.

Albuminuria↗
PubMed1991

Absence of retroviral sequences in Graves' disease.

An earlier report of HIV-1 gene sequences in thyroid cell genomic DNA from patients with Graves' disease prompted use of the polymerase chain reaction technique to identify such sequences in Graves' disease thyroid tissue and in white blood-cells from these patients. We were unable to confirm the existence of HIV-1-related DNA sequences in Graves' specimens.

DNA, Viral↗
PubMed1991

An unsulphated region of the rat chondrosarcoma chondroitin sulphate chain and its binding to monoclonal antibody 3B3.

The chondroitin sulphate chains of proteoglycans are not uniformly sulphated. Commonly, regions of under- and over-sulphation are found. It is probable that variability in chondroitin sulphation has physiological significance, although such structure-function relationships largely remain unexplored. Chondroitin sulphate from rat chondrosarcoma proteoglycan has been found to possess no oversulphated residues. It is primarily chondroitin 4-sulphate, although a significant proportion of unsulphated disaccharides (14%) are also present. It appears that some unsulphated disaccharides are concentrated only at the point of attachment to the linkage region (i.e. it is the major unsaturated disaccharide remaining attached to chondrosarcoma proteoglycan core produced by chondroitinase ABC digestion). This proteoglycan core binds monoclonal antibody (MAb) 3B3. Although 3B3 principally binds to 6-sulphated 'stubs' of proteoglycan cores [Couchman, Caterson, Christner & Baker (1984) Nature (London) 307, 650-652], given a high concentration of unsulphated 'stubs', it can alternatively bind to these residues. It is also evident that caution must be exercised in using MAb 3B3 to identify chondroitin 6-sulphated proteoglycans.

Animals↗
PubMed1991

Influence of the pontine and medullary reticular formation on synchrony of gamma motoneurone discharge in the cat.

Discharges of gamma motoneurones were recorded from cut filaments of the nerve to the gastrocnemius medialis muscle in the cat decerebrated at an intercollicular level. Gamma motoneurones exhibited a background discharge in the absence of intentional stimulation, or could be made to discharge by continuous, innocuous stimulation of the skin of the heel. The discharges were periodic and regular (low coefficient of variation of interspike intervals), and no correlation was observed between the discharges of pairs of individual gamma efferents. Electrolytic lesion of the ipsilateral pontine and medullary reticular formation in the nucleus subcoeruleus, the nucleus reticularis gigantocellularis or the nucleus reticularis magnocellularis, invariably decreased regularity of discharge and resulted in short term synchrony. Lesions of the peri-aqueductal grey, the nucleus raphe dorsalis or the midline raphe nuclei did not induce synchrony. Surgical lesions in the locus coeruleus caused irregular firing and synchrony only when the lesion extended into the adjacent nucleus subcoeruleus. We conclude that monoaminergic neurones of the nucleus subcoeruleus, or a closely associated tegmental field, with axons descending through the gigantocellularis and magnocellularis fields, are the most likely origin of the bulbospinal control of synchronizing influences on gamma motoneurone discharge.

Animals↗
PubMed1991

Thyroid stimulating and thyrotrophin binding-inhibitory immunoglobulin activity in patients with systemic lupus erythematosus having thyroid function abnormalities.

In order to determine whether thyroid function abnormalities seen in patients with systemic lupus erythematosus (SLE) are associated with autoantibodies directed against the TSH receptor, 28 patients with SLE who demonstrated abnormal thyroid function tests were evaluated for the presence of anti-TSH receptor antibodies. Anti-TSH receptor antibody activity was evaluated by assessing cAMP production in vitro in FRTL-5 (rat thyroid) cells (TSI) and the ability of the subjects' IgG to block the binding of thyrotrophin to its receptor in vitro (TBII). Complete thyroid function tests, including TRH testing, also were performed. Ten of the 28 patients demonstrated TSI activity, ranging from 133% to 183% of control. Five patients also had evidence of TBII activity, ranging from 22% to 90% inhibition (of control TSH binding levels), with 2 patients having evidence of both types of antibodies. Neither the TSI nor TBII activity in these patients was associated with the abnormal thyroid function tests. However, there were significantly more patients with TBII activity who had elevated TSH levels (3 of 4 vs 1 of 24, p less than 0.05), suggesting a potential physiologic response to TSH receptor blockade. These results indicate that patients with SLE and thyroid function abnormalities can demonstrate TBII and TSI activity in their serum. However, these antibodies do not necessarily correlate with specific abnormalities of thyroid function.

Antibodies, Antinuclear↗
PubMed1991

Correlation between the discharges of motor units recorded from the same and from different finger muscles in man.

1. Cross-correlation analysis of the discharges of individual motor units recorded from various different finger muscles has been performed during weak, isometric, voluntary contractions in man. 2. The dominant feature in 88% of the cross-correlograms studied was a narrow, central peak, the area of which significantly exceeded that expected for independent processes (P less than 0.001). The highest bin counts in these central peaks were mostly within 5 ms of time zero in the histograms, and the base of these peaks extended between 5 and 31 ms (modal value = 13 ms with 90% of the values lying between 8 and 18 ms). The width and displacement of the central cross-correlogram peaks were similar irrespective of whether the contributory spike trains were recorded from motor units active in the same finger muscle or recorded from motor units in different, co-activated finger muscles. 3. The time course of the central peaks in this study was found to be consistent with the hypothesis that it is generated by the joint occurrence of EPSPs evoked in motoneurones by branches of common stem presynaptic fibres using the theoretical model developed by Kirkwood (Kirkwood & Sears, 1978). The model parameters providing the best fit with our experimental data imply that synaptic contacts on motoneurones made by these common inputs lie on average peripherally in the dendritic tree and generate small (less than 300 microV) EPSPs superimposed on a high level of background synaptic noise. 4. Minima (troughs) were found either side of the central peak in 27% of the cross-correlograms studied, and their appearance was invariably associated with a large central peak. These secondary features could not be modelled with the same operator parameters that describe the central peaks. Their presence was particularly noticed in association with very regular discharges from the output motoneurones. 5. Smaller and broader secondary peaks symmetrically displaced 30-55 ms either side of the large, narrow central peak were observed in 7% of the cross-correlograms studied. We suggest that these secondary features which were found at lags shorter than the interspike interval of the contributory motor unit spike trains reflect the autocorrelation functions of the spike trains of common input fibres. On this basis the observed displacement of these secondary peaks from the primary feature in the cross-correlogram indicate firing rates for common input fibres in the range 18-33 impulses s-1. 6. In a small number of cases (1.4%) the cross-correlogram was flat and indistinguishable from the results of cross-correlating independent spike train data.

Action Potentials↗
PubMed1991

Variation in the degree of synchronization exhibited by motor units lying in different finger muscles in man.

1. Cross-correlation analysis was performed on the discharges of motor units recorded from the same or from different finger muscles during weak, voluntary isometric contractions in man. 2. In 88% of cases such cross-correlograms contained a narrow central peak indicating synchronization between the firing of the contributory motor units. Expressed in terms of the synchronization index, b (peak area/total number of reference plus response spikes) the amount of synchronization found in these different recordings ranged from b = 0.0057 to b = 0.1436 (n = 1230). The duration of the synchronization (measured across the base of the peak) ranged from 5 to 31 ms (mode = 13 ms). 3. For each pair of motor units examined the amount of synchronization between their firing varied from minute to minute of a long recording. In around half the cases studied this variation appeared to correspond to variation in the firing rates of the two motor units whereas in the other half of cases tested no relationship was found between the firing rates and the amount of synchronization. 4. Some motor unit pairings consistently showed more synchronization than other motor unit pairings within the same muscle. A frequency histogram of the synchrony measurements from all of the motor unit pairings tested in that muscle showed a unimodal and continuous distribution. 5. Some subjects consistently showed two or three times more motor unit synchronization than others in equivalent recordings. This rank order of motor unit synchronization in different subjects was found to be the same in all muscle pairings tested. 6. A similar distribution in the amount of motor unit synchronization found in different muscle pairings was found in all subjects tested. In the first place the firing of motor units which act on widely separated fingers was less synchronized than the firing of motor units acting on adjacent fingers. Secondly, motor units acting on the lateral fingers (thumb, index) showed less synchronization in their discharges than motor units acting on medial fingers (ring, little). Finally the firing of motor units in the finger flexor muscles were less synchronized than the firing of motor units in either the finger abductor or the finger extensor muscles. 7. The synchronization of motor unit activity in different muscles indicates the presence of a widespread projection pattern for the branches of some last-order input fibres to finger muscle motoneurones.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1991

Effect of task on the degree of synchronization of intrinsic hand muscle motor units in man.

1. Recordings were made of the firing of pairs of intrinsic hand muscle motor units active under different task conditions in man. The different tasks were defined as isometric contractions producing force in one of three different directions: finger abduction, finger extension, or finger flexion. The degree of motor-unit synchronization associated with each of these task conditions was compared with the use of cross-correlation analysis. 2. The average amount of synchronization between the firing of motor units recorded from within first dorsal interosseous muscle (IDI) was greater during index finger extension than during index finger abduction (n = 8 motor-unit pairings, 3 subjects). In addition, for another sample population of motor units, the average amount of synchronization was greater during index finger abduction than during index finger flexion (n = 11 motor-unit pairings, 4 subjects). 3. In a further series of experiments, one motor unit of each pair was recorded from second dorsal interosseous muscle (2DI), whereas the other motor unit of each pair was recorded from 1DI. The average amount of synchronization for these motor-unit pairings was greater during extension of the index and middle fingers than during abduction of the index and middle fingers (n = 8, 4 subjects). For another sample population of such motor-unit pairings, the average amount of synchronization was found to be greater during abduction of the index and middle fingers than during flexion of the index and middle fingers (n = 11, 4 subjects). 4. In approximately one-third of cases, it was not found possible to maintain the same firing rates from two motor units in 1DI when active under different task conditions. For instance, the "reference" motor unit might consistently fire at a faster rate than the "response" motor unit when active during index finger extension but consistently fire at a slower rate than the response motor unit when active during index finger abduction. Where such motor-unit pairs have been studied in detail, the pattern of task dependence in their synchronization was found to be similar to that described above for motor-unit pairs in which the firing rates remained constant under the different task conditions.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1991

Taxonomy, evolution and life cycles.

Three lectures were given, the first on haplodiploidy in the Oxyurida (Nematoda), the second on rodent Oxyurida and the third on the life cycle of Leishmania (Kinetoplastida, Trypanosomatidae). The oral communications and posters were divided into five subsections, covering systematics at supraspecific, specific and subspecific levels, evolution, and life cycles of parasites with hosts in both aquatic and terrestrial environments. A wide range of topics was discussed, including recent developments in the fields of genetics and cellular and molecular biology, and computer-assisted numerical taxonomy.

Animals↗
PubMed1991

The immunopathogenesis of AIDS.

In summary, the understanding of the pathogenesis of immune dysfunction in HIV infection is incomplete. New mechanisms by which HIV disrupts the immune system through alterations in basic biochemical events in CD4 T cells are continually being discovered. In a positive light, because of the complexity involved in HIV-mediated induction of immune suppression, logic suggests there is potential for reversing some of these processes.

Acquired Immunodeficiency Syndrome↗
PubMed1990

A competitive assay of lipoprotein: proteoglycan interaction using a 96-well microtitration plate.

A method for the microassay in vitro of lipoprotein: proteoglycan interactions is described. The wells of a plastic 96-well microtitration plate are coated with low density lipoprotein. A limiting quantity of biotin-conjugated proteoglycan is allowed to bind to each coated well, and the amount of the latter retained in wells is estimated spectrophotometrically through subsequent binding of alkaline phosphatase-conjugated avidin. Many of the incubation parameters (e.g., time, pH, salt concentration, divalent cations), which influence the extent of binding of biotin-conjugated proteoglycan, have been studied and optimized. The effect upon binding of introducing different levels of proteoglycans or lipoproteins at the interaction step can be measured readily. Thus, the orders of increasing relative binding affinities were found to be high density lipoprotein less than Lipoprotein (a) less than low density lipoprotein; rat chondrosarcoma proteoglycan less than bovine nasal cartilage proteoglycan less than human aorta proteoglycan; chondroitin 4-sulfate less than chondroitin 6-sulfate less than dermatan sulfate for lipoproteins, proteoglycans, and glycosaminoglycans, respectively.

Animals↗
PubMed1990

Rapid detection of spatial pattern by Fourier analysis.

Fast Fourier transform analysis can be used to accurately and rapidly detect pattern in large two-dimensional arrangements of points, such as the locations of cells in culture or plants in a unit square. We present here a sample study of pattern in spatial random point processes. This is evidently the first time that Fourier transform-based cross-correlation techniques have been applied to the analysis of point processes of biological origin. Radial profiles of the power spectra and autocorrelation estimates revealed a nearly constant interpore distance of 0.49 +/- 0.04 mm in the locations of eccrine gland pores on the surface of human skin. Additionally, gland-free areas may exist near hair follicles.

Algorithms↗
PubMed1990

Effects of beta-D-xyloside on morphogenesis and cytodifferentiation in cultured embryonic mouse molars.

Embryonic mouse molars were grown on a semi-solid medium supplemented with 2 mM beta-D-xylopyranoside (beta-xyloside), a specific inhibitor of proteoglycan synthesis. The induced glycosaminoglycan depletion in the extracellular matrix was monitored by immunohistochemistry employing monoclonal antibodies to chondroitin 4- and chondroitin 6-sulfates. beta-Xyloside inhibited formation of the dental bell and delayed the appearance of the first odontoblasts. Odontoblast functional differentiation proceeded in the absence of chondroitin sulfate in the basement membrane. Predentin secreted in the presence of beta-xyloside triggered the polarization of ameloblasts, but did not allow the maintenance of polarized odontoblasts. These results support the hypothesis that, in the tooth germ, chondroitin sulfate proteoglycans participate in the regulation of cell kinetic-dependent morphogenesis (Mark et al., 1990. Differentiation 43, 37-50). On the other hand, the possibility that chondroitin sulfate might play a role in odontoblast terminal differentiation is definitively ruled out.

Ameloblasts↗