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Biomedical subjects

D Chambers

Publications and source records attributed to D Chambers.

At least 37 records · Page 2Linked to original sources
PubMed1999

Long-term myocardial preservation: beneficial and additive effects of polarized arrest (Na+-channel blockade), Na+/H+-exchange inhibition, and Na+/K+/2Cl- -cotransport inhibition combined with calcium desensitization.

BACKGROUND: Polarized arrest, induced by tetrodotoxin (TTX) at an optimal concentration of 22 micromol/L, has been shown to reduce ionic imbalance and improve myocardial preservation compared with hyperkalemic (depolarized) arrest. Additional pharmacologic manipulation of ionic changes (involving inhibition of Na+ influx by the Na+/H+ exchanger [HOE694] and Na+/K+/2Cl- cotransporter [furosemide], and calcium desensitization [BDM]) may further improve long-term preservation. In this study, we (i) established optimal concentrations of each drug, (ii) determined additive effects of optimal concentrations of each drug and (iii) compared our optimal preservation solution to an established depolarizing cardioplegia (St Thomas' Hospital solution No 2: STH2) used during long-term hypothermic storage for clinical transplantation. METHODS: The isolated working rat heart, perfused with Krebs Henseleit (KH) buffer was used; cardiac function was measured after 20 min aerobic working mode perfusion. The hearts (n=6/group) were arrested with a 2 ml infusion (for 30 sec) of the polarizing (control) solution (22 micromol/L TTX in KH) or control+drug and subjected to 5 hr or 8 hr of storage at 7.5 degrees C in the arresting solution. Postischemic function during reperfusion was measured (expressed as percentage of preischemic function). RESULTS: Dose-response studies established optimal concentrations of HOE694 (10 micromol/L), furosemide (1.0 micromol/L) and BDM (30 mmol/L) in the polarizing (control) solution. Sequential addition to the control solution (Group I) of optimal concentrations of HOE694 (Group II), furosemide (Group III), and BDM (Group IV) were compared with STH2 (Group V); postischemic recovery of aortic flow was 29+/-7%, 49+/-6%*, 56+/-2%*, 76+/-3%*, and 25+/-6%, respectively (*P<0.05 vs. I and V). Creatine kinase leakage was lowest, and myocardial ATP content was highest in Group IV. CONCLUSIONS: A polarizing preservation solution (KH+TTX) containing HOE694, furosemide, and BDM significantly enhanced long-term preservation compared with an optimized depolarizing solution (STH2) used clinically for long-term donor heart preservation.

Adenine Nucleotides↗
PubMed1999

Genomic structure and chromosomal mapping of the murine and human Mbd1, Mbd2, Mbd3, and Mbd4 genes.

DNA methylation is essential for murine development and is implicated in the control of gene expression. MeCP2, MBD1, MBD2, MBD3, and MBD4 comprise a family of mammalian, nuclear proteins related by the presence in each of an amino acid motif called the methyl-CpG binding domain (MBD). Each of these proteins, with the exception of MBD3, is capable of binding specifically to methylated DNA. MeCP2, MBD1 and MBD2 can also repress transcription. We describe the genomic structure and chromosomal localization of the human and murine Mbd1, Mbd2, Mbd3, and Mbd4 genes. We find that the highly similar MBD2 and MBD3 proteins are encoded by genes that map to different chromosomes in humans and mice but show a similar genomic structure. The Mbd1 and Mbd2 genes, in contrast, map together to murine and human Chromosomes (Chrs)18. The Mbd3 and Mbd4 genes map to murine Chrs 10 and 6, respectively, while the human MBD3 and MBD4 genes map to Chrs 19 and 3, respectively.

Animals↗
PubMed1998

Cellular mechanisms of resistance to chronic oxidative stress.

Oxidative stress is implicated in several pathologies such as AIDS, Alzheimer's disease, and Parkinson's disease, as well as in normal aging. As a model system to study the response of cells to oxidative insults, glutamate toxicity on a mouse nerve cell line, HT-22, was examined. Glutamate exposure kills HT-22 via a nonreceptor-mediated oxidative pathway by blocking cystine uptake and causing depletion of intracellular glutathione (GSH), leading to the accumulation of reactive oxygen species and, ultimately, apoptotic cell death. Several HT-22 subclones that are 10-fold resistant to exogenous glutamate were isolated and the mechanisms involved in resistance characterized. The expression levels of neither heat shock proteins nor apoptosis-related proteins are changed in the resistant cells. In contrast, the antioxidant enzyme catalase, but not glutathione peroxidase nor superoxide dismutase, is more highly expressed in the resistant than in the parental cells. In addition, the resistant cells have enhanced rates of GSH regeneration due to higher activities of the GSH metabolic enzymes gamma-glutamylcysteine synthetase and GSH reductase, and GSH S-transferases activities are also elevated. As a consequence of these alterations, the glutamate resistant cells are also more resistant to organic hydroperoxides and anticancer drugs that affect these GSH enzymes. These results indicate that resistance to apoptotic oxidative stress may be acquired by coordinated changes in multiple antioxidant pathways.

Animals↗
PubMed1998

Religious sanctions and rates of suicide worldwide.

In order to understand differences in suicide rates between the countries affiliated to the International Association for Suicide Prevention (IASP), the present paper investigates whether there is a relationship between the existence of religious sanctions and aggregate national suicide rates as reported to the World Health Organization. Through their participation in this study, 49 IASP national representatives reported on the existence of religious sanctions against suicide. It was discovered that countries with religious sanctions were less likely to return rates of suicide to the WHO. Comparative analysis revealed that the average reported rates for countries with sanctions are lower than those for countries without religious sanctions. The difference is particularly significant for females. Overall, then, at an aggregate level, it would appear that an inverse relationship does exist; however, while countries with religious sanctions against suicide return lower rates of suicide, as recorded by the WHO, recording and reporting procedures may be affected by the existence of sanctions, thus diminishing the reliability of reported rates. Furthermore, distinctions between rates among the different denominations seem to have been somewhat blurred, in particular between Catholics and Protestants, to the extent that in certain societies Catholics have a higher reported rate of suicide--despite the fact that, doctrinally, Catholicism is more severe in the condemnation of suicide than the majority of Protestant churches (with a few notable exceptions, such as the Orthodox Calvinists).

Attitude to Health↗
PubMed1998

Euthanasia and related practices worldwide.

The present paper examines the occurrence of matters relating to the ending of life, including active euthanasia, which is, technically speaking, illegal worldwide. Interest in this most controversial area is drawn from many varied sources, from legal and medical practitioners to religious and moral ethicists. In some countries, public interest has been mobilized into organizations that attempt to influence legislation relating to euthanasia. Despite the obvious international importance of euthanasia, very little is known about the extent of its practice, whether passive or active, voluntary or involuntary. This examination is based on questionnaires completed by 49 national representatives of the International Association for Suicide Prevention (IASP), dealing with legal and religious aspects of euthanasia and physician-assisted suicide, as well as suicide. A dichotomy between the law and medical practices relating to the end of life was uncovered by the results of the survey. In 12 of the 49 countries active euthanasia is said to occur while a general acceptance of passive euthanasia was reported to be widespread. Clearly, definition is crucial in making the distinction between active and passive euthanasia; otherwise, the entire concept may become distorted, and legal acceptance may become more widespread with the effect of broadening the category of individuals to whom euthanasia becomes an available option. The "slippery slope" argument is briefly considered.

Ethics, Medical↗
PubMed1998

Euthanasia and the terminally ill: can the civil killing of others be eroded?

The present paper assesses attitudes towards the ending of life among a sample of 100 terminally ill hospice patients. Such a sample best provides an insight into the demand for euthanasia in this most extreme of circumstances. Of the completed interviews (64), 43 patients were fully aware of the implications of their condition; 35 expressed a definite opinion regarding euthanasia, 22 of whom favored the individual's right to choose the timing of death. Only 6 of these 22 were fully competent at the time of the interview and were not suffering from any depressive disorder. The implications of these results point to the need to consider the prevalence of depression, anxiety, and related disorders among those who seek an end to life. A failure to do so is likely to affect legislation worldwide, and, in turn, civilization itself.

Attitude to Death↗
PubMed1997

Does hyperglycaemia have an influence upon colour vision of patients with diabetes mellitus?

It has been suggested that variations found in colour vision upon repeated testing may be due to fluctuations in the plasma glucose level, but the results of studies to date are conflicting. Therefore, the aim of this study was to investigate whether a short-term increase in plasma glucose concentration had an influence on colour vision in patients with non insulin-dependent diabetes mellitus (NIDDM) (n = 16). The colour vision and plasma glucose levels were monitored every 30 min for a total period of 4 h during three test conditions: two when the plasma glucose levels were increased by the administration of glucose, either orally (n = 8) or intravenously (n = 8), and one when the plasma glucose was relatively stable during fasting conditions (n = 8). The results indicate that the colour vision, as assessed by the Desaturated D15, appears to be unaffected by the short-lived increases in plasma glucose concentrations.

Aged↗
PubMed1996

Stress fracture of the pubic ramus in female recruits.

During a four-month period we observed 12 stress fractures of the inferior pubic ramus in 11 military recruits undergoing basic training. Eleven of these were in women. This high number was considered to be caused by the introduction of mixed training of male and female recruits; this forces women to increase their stride length when marching. The presenting symptom was chronic groin pain which failed to settle with rest, and the clinical diagnoses were confirmed by radiographs in all but one patient who was diagnosed by 99mTc bone scanning. Since the required stride length has been reduced there have been no new cases of stress fracture of the pelvis.

Adolescent↗
PubMed1995

Shigella in Tulsa County, 1993: epidemiology, day care center association, and control.

Tulsa County experienced an epidemic of Shigella sonnei infection and diarrheal disease during 1993. Of the 298 cases documented, 262 occurred in day care centers. There were 227 epidemiologically-linked secondary cases, primarily in parents and siblings. The mode of transmission was primarily person-to-person among family members and children in day care centers. In addition, transmission may also have occurred as the result of fomities in some day care centers. Control was achieved by antibiotic therapy, inspection, and retraining all day care centers' staffs in hand washing techniques and infection control concepts.

Adolescent↗
PubMed1995

Patients who make a dentist most anxious about giving injections.

The patient is not the only person in the dental operatory who may be feeling anxious about injections. A questionnaire mailed to 3,000 alumni of a California dental school of study the effects on dentists of administering local anesthesia showed that they, too, can be anxious during the procedure. Of the 3,000 questionnaires sent out, 711 valid ones were returned. This paper analyzes the answers of 545 respondents to one of the questionnaire's open-ended questions, "Is there one type of patient that seems to make you the most anxious about giving injections? If so, please describe this type of patient." Two-thirds of the responses to this question described anxious patients as the main source of the dentist's anxiety. The next most frequent response (16 percent) identified children as the main source of anxiety. Six percent of the dentists wrote that no particular type of patient bothers them when giving an injection.

Adult↗
PubMed1994

The molecular basis of instability of the singed(very weak) mutation in Drosophila melanogaster.

The singed(very weak) mutation was created by the sequential addition of two P transposable elements to the singed gene. The mutation can be somatically unstable through the action of a dominant maternal effect mutation on the second chromosome. It is also unstable in the germ line in these conditions. Sequencing of the region of the P insertions in the mutation reveals that the two inserted elements have single internal deletions, and the larger of the two is a copy of the KP element. The mutation will generate, at high frequencies, strongly singed and pseudo-wild type products by reversions occurred in the germline. These are the result of the precise excision of the smaller and the larger elements respectively. By PCR amplification of dissected thoraces we show that the somatic instability of the mutation, from a weak to a strong singed phenotype, is also caused by the excision of the smaller of the two elements.

Animals↗
PubMed1994

Analysis of CAG trinucleotide repeats from mouse cDNA sequences.

A number of human single gene disorders are now known to result from abnormal expansion of trinucleotide repeats. Spinal muscular bulbar atrophy, myotonic dystrophy, Huntington's Disease, spinocerebellar ataxia and dentatorubral-pallidoluysian atrophy are all caused by expansions of CAG repeats. Abnormal expansion of trinucleotide repeats has only so far been described in humans, and no mouse models exist for these diseases. In order to investigate trinucleotide repeat stability in mice, the Genbank and EMBL nucleotide databases were screened to find genes containing CAG repeats. Of the sequences selected, 32 were from mouse, and in 12 of these the repeat was in transcribed sequence and contained at least seven perfect repeats. These repeats were then analysed by PCR to evaluate the degree of variability of repeat length in the various genes. Two of the genes containing variable length CAG repeats, seven in absentia homologue 1b (Sinh1b), and choline acetyl transferase (Chat), which had not previously been mapped in the mouse genome, were mapped by linkage analysis in an interspecific backcross. Sinh1b maps very distally on the X chromosome, and Chat maps to chromosome 14.

Animals↗