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Biomedical subjects

C M Saunders

Publications and source records attributed to C M Saunders.

13 recordsLinked to original sources
PubMed2006

PLCzeta(zeta): a sperm protein that triggers Ca2+ oscillations and egg activation in mammals.

At fertilization in mammals, the sperm activates development by causing a prolonged series of intracellular Ca(2+) oscillations that are generated by increased production of inositol trisphosphate (InsP(3)). It appears that the sperm initiates InsP(3) generation via the introduction of a sperm factor into the egg after gamete membrane fusion. We recently identified a sperm-specific form of phospholipase C (PLC), referred to as PLCzeta(zeta). We review the evidence that PLCzeta represents the sperm factor that activates development of the egg and discuss the characteristics of PLCzeta that distinguish it from the somatic forms of PLC.

Amino Acid Sequence↗
PubMed2004

The cytosolic sperm factor that triggers Ca2+ oscillations and egg activation in mammals is a novel phospholipase C: PLCzeta.

When sperm activate eggs at fertilization the signal for activation involves increases in the intracellular free Ca2+ concentration. In mammals the Ca2+ changes at fertilization consist of intracellular Ca2+ oscillations that are driven by the generation of inositol 1,4,5-trisphosphate (InsP3). It is not established how sperm trigger the increases in InsP3 and Ca2+ at fertilization. One theory suggests that sperm initiate signals to activate the egg by introducing a specific factor into the egg cytoplasm after membrane fusion. This theory has been mainly based upon the observation that injecting a cytosolic sperm protein factor into eggs can trigger the same pattern of Ca2+ oscillations induced by the sperm. We have recently shown that this soluble sperm factor protein is a novel form of phospholipase C (PLC), and it is referred to as PLCzeta(zeta). We describe the evidence that led to the identification of PLCzeta and discuss the issues relating to its potential role in fertilization.

Animals↗
PubMed2002

Sperm phospholipase Czeta from humans and cynomolgus monkeys triggers Ca2+ oscillations, activation and development of mouse oocytes.

Fusion with a fertilizing spermatozoon induces the mammalian oocyte to undergo a remarkable series of oscillations in cytosolic Ca(2+), leading to oocyte activation and development of the embryo. The exact molecular mechanism for generating Ca(2+) oscillations has not been established. A sperm-specific zeta isoform of phospholipase C (PLCzeta) has been identified in mice. Mouse PLCzeta triggers Ca(2+) oscillations in mouse oocytes and exhibits properties synonymous with the 'sperm factor' that has been proposed to diffuse into the oocyte after gamete fusion. The present study isolated the PLCzeta homologue from human and cynomolgus monkey testes. Comparison with mouse and monkey PLCzeta protein sequences indicates a shorter X-Y linker region in human PLCzeta and predicts a distinctly different isoelectric point. Microinjection of complementary RNA for both human and cynomolgus monkey PLCzeta elicits Ca(2+) oscillations in mouse oocytes equivalent to those seen during fertilization in mice. Moreover, human PLCzeta elicits mouse egg activation and early embryonic development up to the blastocyst stage, and exhibits greater potency than PLCzeta from monkeys and mice. These results are consistent with the proposal that sperm PLCzeta is the molecular trigger for egg activation during fertilization and that the role and activity of PLCzeta is highly conserved across mammalian species.

Amino Acid Sequence↗
PubMed2001

Tolerability of hormone therapies for breast cancer: how informative are documented symptom profiles in medical notes for 'well-tolerated' treatments?

Hormonal therapies for cancer are often viewed as a gentler option than many other cancer treatments, but is low toxicity an accurate perception of patients' experiences? Side effects tend to be described as minimal or well tolerated, yet published symptoms from hormonal therapy vary considerably in their descriptions and frequencies. Previous research has highlighted under-reporting of side effects by clinical staff so as part of a wider study examining tamoxifen and goserelin treatment as adjuvant therapy for breast cancer, treatment-related symptoms documented in medical notes were compared with those that patients reported during a research interview. There was a significant difference in the frequency of many side effects reported by the two methods in this study. Sixty four out of 72 (89%) women who had received adjuvant tamoxifen or goserelin had side effects recorded in their medical notes, compared with 74/75 (99%) reporting side effects at interview. We compared the published frequencies of commonly reported symptoms with those found ourselves. The discrepancies between patient-reported and clinician-recorded (usually from clinical trial data) symptom profiles were similar to those found in our study. Without accurate comprehensive side effect profiles for hormone therapies, prospective patients cannot make informed judgements on proposed treatments.

Adult↗
PubMed1995

Dehydration and the dying patient.

This study investigated the relationship between symptoms and dehydration in 82 subjects with malignant disease. Assessment of respiratory tract secretions, thirst, and dry mouth were made during the dying phase, and serum biochemistry was analyzed. Follow-up data were also collected when the patient died. The median time from entry into the study until death was 2 days. All subjects died without artificial fluid therapy. Analysis showed that over 50% of subjects had a serum osmolality of less than 295 mOsm/kg. Contrary to previous anecdotal evidence, no statistically significant relationship was demonstrated between the level of hydration and respiratory tract secretions. Twenty-eight percent of subjects were able to respond to questions; 87% of these had a dry mouth and 83% felt thirsty. No statistically significant association was found between level of hydration and these symptoms. Artificial hydration to alleviate these symptoms in the dying patient may, therefore, be futile. Further work needs to be carried out regarding the cause and treatment of these symptoms in the dying patient.

Adult↗
PubMed1995

On withholding nutrition and hydration in the terminally ill: has palliative medicine gone too far? A reply.

Patients who are dying of cancer usually give up eating and then stop drinking. This raises ethical dilemmas about providing nutritional support and fluid replacement. The decision-making process should be based on a knowledge of the risks and benefits of giving or withholding treatments. There is no clear evidence that increased nutritional support or fluid therapy alters comfort, mental status or survival of patients who are dying. Rarely, subcutaneous fluid administration in the dying patient may be justified if the family remain distressed despite due consideration of the lack of medical benefit versus the risks. Some cancer patients who are not imminently dying become dehydrated from reversible conditions such as hypercalcaemia. This may mimic the effects of advanced cancer. These conditions should be sought and fluid replacement therapy should be given along with the specific treatments for the condition.

Brain Diseases↗
PubMedDate not supplied

Quality of life during treatment for cancer.

Assessment of quality of life produces a hard outcome measure of treatment which allows us to tailor therapy to the patient's needs. This article look at ways in which quality of life can be measured and at its clinical importance in the treatment of cancer.

Humans↗
PubMedDate not supplied

Current management of breast cancer.

The last decade has seen many changes in the management of breast cancer, both in surgical treatment and in systemic therapy, which can reduce the mortality rate by 25%. At the same time attention has turned to improving not only length of survival but also quality of life. These changes plus new developments in breast cancer treatment are reviewed here.

Adult↗