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Biomedical subjects

M Gardiner

Publications and source records attributed to M Gardiner.

35 records · Page 2Linked to original sources
PubMed1994

Defined chromosomal assignment of CLN5 demonstrates that at least four genetic loci are involved in the pathogenesis of human ceroid lipofuscinoses.

We demonstrate here that at least four genetically separate loci are involved in the pathogenesis of human neuronal ceroid lipofuscinoses (NCLs), fatal brain disorders of children. Earlier the assignments of the infantile and juvenile subtypes of NCL to 1p32 and 16p12 had revealed two loci; and here a variant subtype of the late-infantile form of NCL is mapped to a well-defined region on 13q21.1-q32, whereas the clinically similar, classical form of late-infantile NCL was found to represent the fourth, yet-unidentified NCL locus. The linkage disequilibrium was crucial for locus assignment in our highly limited family material, and the data exemplify the significance of this phenomenon in the random mapping of rare human diseases.

Child↗
PubMed1990

Batten disease (Spielmeyer-Vogt disease, juvenile onset neuronal ceroid-lipofuscinosis) gene (CLN3) maps to human chromosome 16.

The ceroid-lipofuscinoses are a group of inherited neurodegenerative disorders characterized by the accumulation of autofluorescent lipopigment in neurons and other cell types. The underlying biochemical defect is unknown. Batten disease (Spielmeyer-Vogt disease, juvenile onset neuronal ceroid-lipofuscinosis) displays autosomal recessive inheritance. Genetic linkage studies were undertaken to determine the chromosomal location of the Batten disease mutation (CLN3). Following identification of linkage to the haptoglobin locus, linkage analysis has been carried out in 42 families by using DNA markers for loci on the long arm of human chromosome 16. The maximal lod score between Batten disease and the locus D16S148 calculated for combined sexes is 6.05 at a recombination fraction theta = 0.00. Multilocus analysis using five loci indicated the most likely order to be HP-D16S151-D16S150-CLN3-D16S148-D16S147. The maximal location score for CLN3 was 48 (equivalent to a lod score of 10.4) in that interval within this fixed marker map.

Chromosome Mapping↗
PubMed1985

Sublethal hemorrhage impairs the acute peritoneal inflammatory response in the rat.

Hemorrhagic shock increases the risk of septic complications in injured patients. In this study, we investigated the effect of sublethal hemorrhage on the acute peritoneal inflammatory response and the clearance of bacteria from the peritoneal cavity of the rat. Sprague-Dawley rats were subjected to sublethal hemorrhage, resuscitated, and then inoculated intraperitoneally with a suspension of viable Escherichia coli in saline. Sham-hemorrhaged rats served as controls. Sublethal hemorrhage decreased survival and impaired the influx into the peritoneum of polymorphonuclear leukocytes and macrophage colony-forming cells. There was no difference between groups in the clearance of viable bacteria from the peritoneum; clearance of blood-borne bacteria was decreased in the hemorrhaged animals. We conclude that sublethal hemorrhage in the rat inhibits the acute peritoneal inflammatory response, but has little or no effect on the early removal of bacteria from the peritoneal cavity.

Animals↗
PubMed1983

Reality orientation with elderly patients in the community: an empirical evaluation.

There is now good evidence that elderly mentally impaired patients can be re-orientated for time, place and person using the technique of reality orientation (RO). To date, all empirical trials demonstrating this have been carried out on elderly institutionalized patients. This technique however might be of greater value to those elderly dementing patients still living with relatives in the community but attending geriatric psychiatry day hospitals, where they could receive RO in a consistent and systematic way. The results of an empirical study of RO with a group of such patients is reported. These showed that day hospital patients could be effectively re-orientated and that concomitant with changes in level of orientation of the patients, there were parallel changes in the patients' behaviour at home, reported stress on relatives and in relatives' mood.

Aged↗
PubMed1982

Influence of blood glucose concentration on brain lactate accumulation during severe hypoxia and subsequent recovery of brain energy metabolism.

The effects of hypoxaemia on regional cerebral blood flow (CBF) and brain cortical metabolite concentrations were investigated at different blood glucose concentrations in rats under nitrous oxide anaesthesia. Tissue hypoxia of 15-min duration was induced by a combination of arterial hypoxaemia, hypotension, and clamping of the right carotid artery. Blood glucose concentrations were manipulated by varying the food intake in the 24 h before the experiment, and by glucose administration. Cortical CBF doubled during hypoxia on the intact side, but did not differ significantly from control values on the clamped side. In the clamped hemisphere there was a substantial decrease in adenylate energy charge. At brain tissue glucose concentration of 1 mumol g-1 and above, there was an inverse correlation between adenylate energy charge and brain lactate concentration. In starved animals with mean brain glucose of 0.32 +/- 0.00 mumol g-1, lactate concentration was significantly lower, in spite of equally severe disruption of energy state. Recovery of brain adenylate energy charge was worse in fed and glucose-infused groups than in the fasted group. These results demonstrate that limitation of substrate supply during severe hypoxia in the rat allows enhanced recovery of brain energy metabolism following the hypoxic episode.

Animals↗
PubMed1982

Measuring behavioural disturbance of elderly demented patients in the community and its effects on relatives: a factor analytic study.

In recent years increasing interest has centered on the elderly psychogeriatric patient living in the community and the part played by relatives in supporting these patients. There is a need, however, for ways of assessing the behavioural disturbance shown by such patients at home and the effect this behaviour has on relatives. Ratings by relatives of the behaviour at home of elderly dementing patients attending a geriatric psychiatry day hospital, together with the relatives' own ratings of the degree of stress and upset being experienced were obtained. Using the technique of factor analysis was shown that the patient's behaviour and the relative's reaction could be analysed into a number of separate categories and that these were differentially related to each other. Thus, for example, personal distress in the relative was related mainly to the amount of apathetic and withdrawn behaviour shown by the patient, whereas negative feelings held by the relative towards the patient were related only to the degree of disturbance of the patient's mood. The construction of scales measuring these different aspects of patient's behaviour and relative's reaction is described.

Aged↗
PubMed1981

Free fatty acids in the rat brain in moderate and severe hypoxia.

The effects of mild, moderate, and severe hypoxia on cerebral cortical concentrations of free fatty acids (FFAs) were investigated in artificially ventilated rats under nitrous oxide anaesthesia. No change occurred during either mild (arterial PO2 35-40 mm Hg) or moderate (PO2 25-30 mm Hg) hypoxia. The effects of severe hypoxia (PO2 about 20 mm Hg) combined with hypotension (mean arterial blood pressure 80-85 mm Hg) varied with the EEG pattern and the tissue energy state. Thus, a major increase in total as well as in individual FFAs occurred first when EEG was severely depressed (almost isoelectric) and energy homeostasis disrupted. On a relative basis the greatest change occurred in free arachidonic acid. It is concluded tha hypoxia is associated with an increase in the concentrations of FFAs in brain tissue, provided that tissue oxygen deficiency is severe enough to cause tissue energy failure. However, an increase in FFAs does not invariably accompany minor reductions in the adenylate energy charge (EC) of the tissue.

Adenine Nucleotides↗
PubMed1981

Indomethacin improves survival in gram-negative sepsis.

A clinically relevant rat model of peritoneal sepsis was developed through the use of (a) intraperitoneal insertion of rat fecal pellets or (b) live E. coli intraperitoneal injections. Therapy with indomethacin and lidocaine were evaluated in this model. Indomethacin alone, or in combination with appropriate antibiotics, significantly improved survival. Lidocaine did not show an increase in survival. These findings suggest that indomethacin may be beneficial in treatment of human sepsis.

Animals↗
PubMed1977

The prevalence of calcified upper urinary tract stone disease in a random population--Cumbernauld Health Survey.

It is difficult to obtain the true prevalence of stone disease in community. A proper random sample of a population has been studied and a figure of 3.83% of calcified stones have been found in 2,000 subjects. The significance of biochemical, bacteriological, skeletal and other surgical abnormalities is discussed. It is now possible to study individual groups within the population with respect to stone disease.

Adolescent↗
PubMed1977

Hemispheric specialization of language: an EEG study of bilingual Hopi indian children.

Electroencephalographic (EEG) recordings were obtained from electrode placements over the left and right frontal and parietal lobes of the brain in sixteen Hopi Indian children listening to tape recorded children's stories in the Hopi and English languages. Spectral analysis of the EEG data revealed that, for the parietal leads, alpha desynchronization was relatively greater over the right hemisphere for listening to Hopi than for listening to English, which indicates a greater right hemisphere participation in the processing of the Hopi speech. The results of the experiment are directionally consistent with our hypothesis, and imply that linguistic relativity may exist on a neurolinguistic level, such that languages can differ in the relative degree to which they serve as instruments of thought in a propositional, left hemisphere mode, or in an appositional, right hemisphere mode.

Arizona↗
PubMed1975

Involvement of the Golgi Apparatus in the Synthesis and Secretion of Hydroxyproline-rich Cell Wall Glycoproteins.

Pulse labeling of carrot root phloem parenchyma (Daucus carota L. cv. Nantes) tissue with (14)C-proline followed by fractionation of the cytoplasmic organelles on sucrose gradients was used to determine the identity of the membranous organelles involved in the secretion of the hydroxyproline-rich glycoproteins of the cell wall. Identification of the organelles was done through electron-microscopical observations and through the localization of marker enzymes on the sucrose gradients. Enrichment of the organelles involved in secretion was determined by measuring the percentage of the incorporated radioactivity present as (14)C-hydroxyproline. The Golgi apparatus (dictyosome) was found to be a major site of glycoprotein transport. This identification was based on the observed enrichment of dictyosomes paralleling the purification of newly synthesized cell-wall glycoproteins. A marker enzyme for the Golgi apparatus, inosinediphosphatase, banded with the newly synthesized cell wall glycoproteins on sequential isopycnic and rate zonal sucrose gradients. Marker enzymes for the endoplasmic reticulum and the plasma membrane were clearly separated from the dictyosome-rich fraction. UDP-arabinose arabinosyl transferase, an enzyme involved in the glycosylation of the peptide moiety of this glycoprotein, also banded with the dictyosomes on both kinds of gradients. The results suggest an important role of the Golgi apparatus in the biosynthesis and the secretion of the cell wall glycoproteins of higher plants.

Journal Article↗
PubMedDate not supplied

Molecular genetic analysis of neuronal ceroid lipofuscinosis.

The neuronal ceroid lipofuscinoses comprise a group of inherited neurodegenerative disorders characterized by the accumulation of autoflourescent lipopigment in neurones and other cell types. Three main childhood sub-types occur: infantile (Haltia-Santavouri disease, locus CLN1), late-infantile (Jansky-Bielschowsky disease, locus CLN2) and juvenile (Spielmeyer-Sjogren-Vogt, Batten disease, locus CLN3). Inheritance is autosomal recessive. The basic biochemical defect remains unknown. The infantile disease Iocus (CLN1) has been mapped to human chromosome 1p32 and the juvenile disease Iocus (CLN3) to human chromosome 16p12 by linkage analysis. Marker loci in strong allelic association with the disease loci have been identified in each case and haplotype analysis suggests a founder mutation for CLN1 and CLN3. Classical late-infantile disease (CLN2) has been shown not to be an allelic variant of either CLN1 or CLN3. Identification of linked markers has provided a new method for pre-natal diagnosis. Work is in progress to clone CLN1 and CLN3 and to map CLN2. This will allow elucidation of the molecular genetic basis of the neuronal ceroid lipofuscinoses.

Animals↗