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Biomedical subjects

P Saunders

Publications and source records attributed to P Saunders.

At least 37 records · Page 2Linked to original sources
PubMed1997

The mouse Dazla gene encodes a cytoplasmic protein essential for gametogenesis.

RBM and DAZ/SPGY are two families of genes located on the Y chromosome that encode proteins containing RNA-binding motifs, and both have been described as candidate human spermatogenesis genes. Transmission of deletions from father to son has been observed in the case of DAZ, but neither gene family has been shown to be essential for spermatogenesis in human males. The DAZ/SPGY genes are particularly amenable to a knockout approach, as they are found on the Y chromosome in Old World primates and apes, but in other mammals, they are represented only by an autosomal gene, DAZLA, which is also present in Old World primates and apes. It has also been shown that a Dazla homologue is essential for spermatogenesis in Drosophila. Here we show that Dazla protein is cytoplasmic in male and female germ cells, unlike the nuclear RBM protein. Disruption of the Dazla gene leads to loss of germ cells and complete absence of gamete production, demonstrating that Dazla is essential for the differentiation of germ cells.

Animals↗
PubMed1997

Neonatal cleft lip repair: a retrospective review of anaesthetic complications.

A retrospective analysis of the first 50 cases of neonatal cleft lip repair performed at the Hospital for Sick Children is presented. The patient population included 11 expremature infants of less than 45 weeks postconceptual age. There was no mortality at the time of follow-up. There was one case of peroperative hypoxaemia. There was one case of postoperative laryngospasm requiring reintubation. Postoperatively there were four cases of mild hypoxaemia and one patient with transient apnoea. No patients required blood transfusion. Seventy-six percent of patients did not require opioid analgesia. The remainder received a single dose of intramuscular codeine phosphate. The advantages and risks of anaesthesia for cleft lip in the neonatal period are reviewed. Recommendations for safe practice include the selection of gestationally mature infants with no intercurrent illness, avoidance of opioid analgesia, adequate staffing ratios of experienced postoperative nursing care, appropriate monitoring including oximetry and apnoea detectors.

Anesthesia, General↗
PubMed1997

Paying for water.

Water has been taken for granted as an essential public health need since the Victorian sanitary revolution. Water has come back on to the public health agenda in the United Kingdom because of recent policy changes and their untoward environmental and social impacts; along with water privatization and tough new environmental directives, there have been serious water pollution incidents, water shortages, water debt and disconnection. Along with concern about protecting individual rights to a clean safe water supply, there is concern about the ability of national water resources to meet all our communities' needs, without unacceptable environmental damage. A national plan is needed for the conservation of water and protection of water resources and the environment; adequate central funds are needed to see that this happens. There should be greater emphasis on local water management and a key role for local authorities; there should be fair pricing, protection of water supplies for the poorest and most vulnerable, and a ban on water disconnection to domestic users, on public health grounds. More research is needed into the potential adverse health impact of people on prepayment meters disconnecting themselves. There is a place for water metering as the most rapidly deliverable means of controlling peak demand, reducing overall consumption and avoiding a large-scale environmentally damaging solution to supply more water. However, control of leakage offers the largest potential saving and is the most cost-effective means to protect existing water supply. We question whether private water companies, geared to maximizing profit and share dividends, can deliver a national plan for the protection and management of water resources, for the good of the environment and future generations. The public health lobby must become more actively engaged in the debate about the supply, protection and price of our most precious public health asset-water.

Environmental Health↗
PubMed1996

Evidence that glyceraldehyde-3-phosphate dehydrogenase is involved in age-induced apoptosis in mature cerebellar neurons in culture.

Under typical culture conditions, cerebellar granule cells die abruptly after 17 days in vitro. This burst of neuronal death involves ultrastructural changes and internucleosomal DNA fragmentations characteristic of apoptosis and is effectively arrested by pretreatment with actinomycin-D and cycloheximide. The level of a 38-kDa protein in the particulate fraction is markedly increased during age-induced cell death and by pretreatment with NMDA, which potentiates this cell death. Conversely, the age-induced increment of the 38-kDa particulate protein is suppressed by actinomycin-D and cycloheximide. N-terminal microsequencing of the 38-kDa protein revealed sequence identity with glyceraldehyde-3-phosphate dehydrogenase (GAPDH). A GAPDH antisense oligodeoxyribonucleotide blocks age-induced expression of the particulate 38-kDa protein and effectively inhibits neuronal apoptosis. In contrast, the corresponding sense oligonucleotide of GAPDH was completely ineffective in preventing the age-induced neuronal death and the 38-kDa protein overexpression. Moreover, the age-induced expression of the 38-kDa protein is preceded by a pronounced increase in the GAPDH mRNA level, which is abolished by actinomycin-D, cycloheximide, or the GAPDH antisense, but not sense, oligonucleotide. Thus, our results suggest that overexpression of GAPDH in the particulate fraction has a direct role in age-induced apoptosis of cerebellar neurons.

Aging↗
PubMed1995

Cloning and expression of a rat placental cDNA encoding a novel cathepsin L-related protein.

Cathepsin L is a major lysosomal cysteine protease produced by mouse placenta and fibroblasts. This study characterizes a novel cathepsin L-related mRNA expressed in rat placenta. Immunological and nucleotide screening of a rat placenta library identified six positive clones, the largest, pCLRP-9, being 924 base pairs in length. The combined sequences of all the clones contain an open reading frame of 711 nucleotides, a termination codon, a polyadenylation site, and 197 nucleotides of 3' untranslated region, but lack the 5' translation initiation codon. The pCLRP nucleotide sequence showed 60-64% identity to those of mouse, rat, and human cathepsin L. The deduced amino acid sequence of pCLRP codes for 237 amino acids, which align with the carboxy-terminal sequence of cathepsin L and has the active site residues characteristic of the cysteine protease family. Northern blot analysis showed hybridization of pCLRP with a major mRNA transcript of 1.3 kilobases expressed in placenta, but not kidney or liver. In contrast, a cDNA for mouse pro-cathepsin L hybridized with a transcript of 1.7 kilobases expressed in rat kidney, as well as placenta. During late gestation, steady-state levels of rat placental pCLRP mRNA were highest on day 18, whereas those of mouse procathepsin L were greatest on day 20 of gestation. Antiserum to mouse cathepsin L cross-reacted with four proteins of molecular weights 36,000 to 42,000 in rat placental culture medium, of which two were absent in the kidney. These data indicate that rat placenta expresses several species of cathepsin L-type proteins, which may be involved in placental function and nutrient supply.

Amino Acid Sequence↗
PubMed1994

An inexpensive device for perioperative positioning of pediatric patients.

Intraoperative positioning of the pediatric patient during venous access procedures is crucial. Currently such patients are positioned with a sandbag beneath the shoulders and in a head-down position. This has significant limitations because the bag must be removed for subsequent on-table radiography. The authors have devised a simple inexpensive technique that obviates this need and facilitates the procedure. They have used the device in over 80 patients undergoing venous access. No problems relating to the device have been noted, and on-table x-rays are readily facilitated.

Catheterization, Central Venous↗
PubMed1991

The epidemiology of dementia: GMS-AGECAT studies of prevalence and incidence, including studies in progress.

The paper reviews the main studies using the AGECAT computerised diagnostic system for the diagnosis of dementia in community studies of prevalence and incidence. It is suggested that variations in reported rates may be due to the use of unstandardised methods, and the paper reviews the oldest established standardised interview: the Geriatric Mental State. The AGECAT system is outlined, and the studies of its diagnostic validity indicated. Arguments are presented against the inclusion of cognitive tests in such instruments, and for the critical evaluation of the concepts of mild dementia. The use of AGECAT in the US/UK Diagnostic Project, and in the Liverpool study of Continuing Health in the Community is described. In addition, preliminary information is given on the Liverpool ALPHA study, the MRC UK multi-centre study, studies organised by the Pan American Health Organisation (Argentina, Chile, Cuba), the Eurodem concerted action (based in Rotterdam) and the WHO multi-site studies. Individual studies in Spain and Portugal are also discussed.

Aged↗
PubMed1989

Improvement of platelet counts in steroid-unresponsive idiopathic immune thrombocytopenic purpura after short-course therapy with recombinant alpha 2b interferon.

In 13 patients with severe steroid-refractory idiopathic immune thrombocytopenia (ITP), a short course of recombinant alpha 2b interferon (IFN), given at a dose of 3 MU for 12 doses, caused a significant increase in platelet count in 11 patients. The rise in platelet count occurred following completion of the short course of IFN in 10 patients and occurred during therapy in one patient. Three patients showed an increase to normal platelet counts within 14 days of discontinuing the drug, eight showed a partial response, with a platelet count increase from 30 to 100 x 10(9)/L, and two patients showed minimal response. One complete responder relapsed at 5 months from initial response, and a further course of alpha 2b IFN caused a second prompt response with a rise of platelet count to supranormal levels. Short-course alpha 2b IFN can be recommended as a therapy for severe ITP. Responses are seen in splenectomized and nonsplenectomized subjects, and thrombocytopenia is not exacerbated during treatment.

Autoimmune Diseases↗
PubMed1988

A comparative study of combination chemotherapy versus marrow transplant in first remission in adult acute lymphoblastic leukaemia.

The results of conventional chemotherapy in adult acute lymphoblastic leukaemia (ALL) have not improved substantially in recent years. The present study is based on a flexible policy of marrow transplantation (allograft and autograft without marrow purging) in first remission compared with a group treated with standard maintenance therapy after a common induction sequence. The actuarial disease free survival (DFS) and actuarial overall survival (OS) at 3 years for autologous marrow grafted patients was 30% and 65% respectively. The allogeneic transplant group had DFS of 30% and OS at 3 years of 38% compared with DFS (12%) and OS (12%) for patients on 6-mercaptopurine and methotrexate maintenance. The actuarial disease free survival calculations include patients on protocol not entering remission, therefore, giving the worst possible result. We conclude that high dose chemo/radiotherapy with autologous marrow rescue in first remission followed by no maintenance provides better results in terms of overall survival and quality of life than standard ALL maintenance in adult patients. Results for allogeneic transplant in ALL are less good in terms of duration and quality of survival and the majority of deaths are related to causes other than leukaemic relapse.

Adolescent↗