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Biomedical subjects

K Mills

Publications and source records attributed to K Mills.

At least 55 records · Page 3Linked to original sources
PubMed1998

Application of magnetic chromatography to the isolation of lysosomes from fibroblasts of patients with lysosomal storage disorders.

A method for the purification of lysosomes from fibroblasts has been developed which uses endocytosis of superparamagnetic colloidal iron dextran particles followed by separation of the iron-containing lysosomes in a magnetic field. This permitted isolation of lysosomes from fibroblasts from patients with infantile sialic acid storage disorder and other lysosomal storage diseases in which a shift in lysosomal density induced by the storage material prevents purification by centrifugation in a Percoll gradient. The magnetic lysosomes isolated from these cells are very similar to those from normal cells as judged by lysosomal marker enzyme activity and 2D-PAGE analysis of the enriched proteins.

Cell Fractionation↗
PubMed1998

Calcium channel antagonist isradipine attenuates cocaine-induced motor activity in rats: correlation with brain monoamine levels.

Cocaine is a widely abused psychomotor stimulant which acts in the central nervous system (CNS) by blocking the reuptake site. It has been estimated that between 30-60 million people have abused cocaine in the United States. Unfortunately, an effective therapy for cocaine abuse is not available. The calcium channel antagonists (CCAs) are commonly used in the therapy of various cardiovascular diseases and are under investigation due to their potential in modulating calcium-dependent neurotransmitter release. The purpose of this study was to evaluate the acute effect of isradipine on cocaine-induced locomotor and stereotypic activity and correlate the changes in dopamine, serotonin and their metabolites--dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), AND 5-hydroxyindoleacetic acid (5-HIAA)--levels in the rat brain. Animals were pretreated intraperitoneally (i.p.) with vehicle or CCAs. After 30 minutes they were administered cocaine (20 mg/kg, i.p.). During this period, motor and stereotypic activity was monitored. In a separate experiment, animals were dosed as described above and were sacrificed by decapitation after the 30-minute treatment period. The nucleus accumbens and caudate nucleus were dissected and analyzed for monoamines using a high-performance liquid chromatography-electrochemical detector (HPLC-ECD). Isradipine (5mg/kg, i.p.) inhibited cocaine-induced locomotor and stereotypic activity by 49% and 36%, respectively, as compared to controls. In the nucleus accumbens cocaine (20 mg/kg, i.p.) increased extracellular dopamine and serotonin levels in the nucleus accumbens by 8% while decreasing serotonin levels by 9%. Cocaine (20 mg/kg, i.p.) produced increased levels of both extracellular dopamine and serotonin (9% and 4%, respectively) in the caudate nucleus. Isradipine (5 mg/kg, i.p.) pretreatment decreased cocaine (20 mg/kg i.p.)-induced extracellular dopamine and serotonin levels in the caudate nucleus by 18% and 8%, respectively. These experiments suggest that a central mechanism may involved in attenuation of cocaine-induced motor behaviors by isradipine.

Animals↗
PubMed1998

Clinical phenotype of desmosterolosis.

We describe a child with lethal multiple malformations and generalised accumulation of desmosterol. The infant had macrocephaly, a hypoplastic nasal bridge, thick alveolar ridges, gingival nodules, cleft palate, total anomalous pulmonary venous drainage, ambiguous genitalia, short limbs, and generalised osteosclerosis. Gas chromatography-mass spectrometry demonstrated an abnormal accumulation of desmosterol in kidney, liver. and brain. Higher than normal levels of the same sterol were detected in plasma samples obtained from both parents. The biochemical phenotype in this infant is highly suggestive of a novel inborn error of cholesterol biosynthesis caused by an autosomal recessive deficiency of 3betahydroxysterol-delta24-reductase. A phenotypic overlap of this case with Raine syndrome was noted; however, desmosterol accumulation was not found on postmortem tissue samples from a previously reported case of this disorder.

Abnormalities, Multiple↗
PubMed1998

Molecular mechanisms of yeast aging.

The life cycle of many organisms involves a progressive decline in fitness and fecundity with age, and yeast is no exception. Many theories have been proposed to explain the mortality of yeast cells, including the increase in cell size and accumulation of bud scars on the cell surface. None of these has survived closed scrutiny. However, recent discoveries might have validated one aging model in which the triggering of a molecular aging clock results in the replication and accumulation of a senescence factor that eventually overwhelms old cells.

DNA, Fungal↗
PubMed1998

Compliance with anti-tuberculosis preventive therapy among 6-year-old children.

There are no published data regarding compliance with anti-tuberculosis preventive therapy among children in Australia and limited published data worldwide. This study aimed to determine the compliance rate among 6-year-old children prescribed preventive therapy for tuberculosis infection. A prospective cohort study was conducted on 78, 6-year-old children prescribed antituberculosis preventive therapy. Compliance was measured by compliance with prescribed preventive therapy as reported by parents who were administered questionnaires on completion of the course. In a subsample of 44 children, the proportion of children who complied with scheduled visits to the hospital, and pharmacy records of isoniazid dispensed were used as measures of compliance. Questionnaire data indicated a reported compliance rate for completion of the 6-month course of preventive therapy of 70.5% (55 children). For those 55 who reported completing the full course, 91% reported missing less than 1 tablet per week. In the subsample of 44 children, only 59% attended all follow-up clinic visits, and 54% collected all 6 months of isoniazid prescribed. Compliance with antituberculosis preventive therapy is suboptimal. Improved methods to measure compliance and strategies to optimise compliance with preventive therapy is required.

Antitubercular Agents↗
PubMed1998

Aging in Saccharomyces cerevisiae.

The budding yeast Saccharomyces cerevisiae divides asymmetrically, giving rise to a mother cell and a smaller daughter cell. Individual mother cells produce a finite number of daughter cells before senescing, undergoing characteristic changes as they age such as a slower cell cycle and sterility. The average life span is fixed for a given strain, implying that yeast aging has a strong genetic component. Genes that determine yeast longevity have highlighted the importance of such processes as cAMP metabolism, epigenetic silencing, and genome stability. The recent finding that yeast aging is caused, in part, by the accumulation of circular rDNA molecules has unified many seemingly disparate observations.

Animals↗
PubMed1998

Sporadic chromosome abnormalities in human lymphocytes and previous exposure to chemicals.

Sporadic abnormalities in lymphocyte cultures are often attributed to in vitro culture variations of no clinical significance. The data presented here compare the findings from 11,873 cells of 230 patients referred with histories of previous chemical exposure (usually to mixtures of solvents and/or pesticides) with 27,050 cells from 855 patients referred for other reasons. Detection of 0.38% or more, structural abnormalities (approximately 1 in 30 cells) was 27.2 times more likely in exposed persons than in controls and the finding of a single autosomal trisomic cell was 14.4 times more likely in exposed persons. These highly statistically significant findings were similar to the frequencies of abnormalities reported in other studies of persons exposed to benzene, pesticides, herbicides and irradiation. It is recommended that findings of sporadic abnormalities in lymphocytes be routinely recorded, and patients with positive findings followed up to discover whether there are past histories of significant exposures.

Adolescent↗
PubMed1997

Accelerated aging and nucleolar fragmentation in yeast sgs1 mutants.

The SGS1 gene of yeast encodes a DNA helicase with homology to the human WRN gene. Mutations in WRN result in Werner's syndrome, a disease with symptoms resembling premature aging. Mutation of SGS1 is shown to cause premature aging in yeast mother cells on the basis of a shortened life-span and the aging-induced phenotypes of sterility and redistribution of the Sir3 silencing protein from telomeres to the nucleolus. Further, in old sgs1 cells the nucleolus is enlarged and fragmented-changes that also occur in old wild-type cells. These findings suggest a conserved mechanism of cellular aging that may be related to nucleolar structure.

Cell Division↗
PubMed1997

Redistribution of silencing proteins from telomeres to the nucleolus is associated with extension of life span in S. cerevisiae.

A prior genetic study indicated that activity of Sir silencing proteins at a hypothetical AGE locus is essential for long life span. In this model, the SIR4-42 mutation would direct the Sir protein complex to the AGE locus, giving rise to a long life span. We show by indirect immunofluorescence that Sir3p and Sir4p are redirected to the nucleolus in the SIR4-42 mutant. Furthermore, this relocalization is dependent on both UTH4 a novel yeast gene that extends life span, and its homologue YGL023. Strikingly, the Sir complex is relocalized from telomeres to the nucleolus in old wild-type cells. We propose that the rDNA is the AGE locus and that nucleolar function is compromised in old yeast cells in a way that may be mitigated by targeting of Sir proteins to the nucleolus.

Cell Cycle Proteins↗
PubMed1997

Primary orthostatic tremor with prominent muscle hypertrophy.

A 33-year-old woman had a 6-year history of progressive postural instability on standing and with walking. There was progressive asymmetric lower limb muscle hypertrophy affecting thigh and calf musculature. Surface EMG recordings showed the rapid development of a synchronized motor unit discharge at a frequency of 17.5 Hz on standing, characteristic of primary orthostatic tremor. These observations suggest that primary orthostatic tremor can be associated with gait disturbance and should be considered in the differential diagnosis of unexplained muscle hypertrophy.

Adult↗
PubMed1996

A novel Ca2+-binding protein, p22, is required for constitutive membrane traffic.

We have identified a novel protein, p22, required for "constitutive" exocytic membrane traffic. p22 belongs to the EF-hand superfamily of Ca2+-binding proteins and shows extensive similarity to the regulatory subunit of protein phosphatase 2B, calcineurin B. p22 is a cytosolic N-myristoylated protein that undergoes conformational changes upon binding of Ca2+. Antibodies against a p22 peptide block the targeting/fusion of transcytotic vesicles with the apical plasma membrane, but recombinant wild-type p22 overcomes that inhibition. Nonmyristoylated p22, or p22 incapable of undergoing Ca2+-induced conformational changes, cannot reverse the antibody-mediated inhibition. The data suggest that p22 may act by transducing cellular Ca2+ signals to downstream effectors. p22 is ubiquitously expressed, and we propose that its function is required for membrane trafficking events common to many cells.

Amino Acid Sequence↗
PubMed1996

Cataracts, motor system disorder, short stature, learning difficulties, and skeletal abnormalities: a new syndrome?

We present a 4-generation family in which affected individuals have cataracts, a motor neuronopathy with upper motor neuron signs, short stature, developmental delay, and skeletal abnormalities. An additional symptom is weakness during pregnancy which resolves after delivery. The condition is inherited in an autosomal dominant manner. The manifestations and inheritance are not found in any previously described conditions. We consider that this is a new syndrome.

Abnormalities, Multiple↗