Search PubMed⌕ Search

Biomedical subjects

S Sanders

Publications and source records attributed to S Sanders.

At least 37 records · Page 2Linked to original sources
PubMed1998

Increased Abeta42(43) from cell lines expressing presenilin 1 mutations.

Mutations in the presenilin 1 (PS1) gene on chromosome 14 are a major cause of autosomal dominant, early-onset Alzheimer's disease. Here, we show that transfecting cells with several mutant, but not wild-type, PS1 cDNAs alters the processing of the amyloid precursor protein (APP) such that more Abeta42(43) is produced, confirming and extending several recent reports. The most effective mutation in this regard was the exon 9 splice-out mutation (delta9). The correlation between the size of the effect on APP processing and the age of onset of disease assessed in families with the mutations was not informative, and the possible reasons for this are discussed.

Age of Onset↗
PubMed1998

Accelerated Alzheimer-type phenotype in transgenic mice carrying both mutant amyloid precursor protein and presenilin 1 transgenes.

Genetic causes of Alzheimer's disease (AD) include mutations in the amyloid precursor protein (APP), presenilin 1 (PS1), and presenilin 2 (PS2) genes. The mutant APP(K670N,M671L) transgenic line, Tg2576, shows markedly elevated amyloid beta-protein (A beta) levels at an early age and, by 9-12 months, develops extracellular AD-type A beta deposits in the cortex and hippocampus. Mutant PS1 transgenic mice do not show abnormal pathology, but do display subtly elevated levels of the highly amyloidogenic 42- or 43-amino acid peptide A beta42(43). Here we demonstrate that the doubly transgenic progeny from a cross between line Tg2576 and a mutant PS1M146L transgenic line develop large numbers of fibrillar A beta deposits in cerebral cortex and hippocampus far earlier than their singly transgenic Tg2576 littermates. In the period preceding overt A beta deposition, the doubly transgenic mice show a selective 41% increase in A beta42(43) in their brains. Thus, the development of AD-like pathology is substantially enhanced when a PS1 mutation, which causes a modest increase in A beta42(43), is introduced into Tg2576-derived mice. Remarkably, both doubly and singly transgenic mice showed reduced spontaneous alternation performance in a "Y" maze before substantial A beta deposition was apparent. This suggests that some aspects of the behavioral phenotype in these mice may be related to an event that precedes plaque formation.

Alzheimer Disease↗
PubMed1998

Streptococcal infection observed in the autumn of 1995.

Near patient testing demonstrated an unusual infection pattern with a high incidence of Lancefield group D beta-haemolytic streptococci in patients with pharyngitis and tonsillitis in a London general practice. This raises questions regarding the epidemiology of this streptococcus strain, which is not usually associated with upper respiratory infections.

Female↗
PubMed1998

The effect of mitomycin C on Molteno implant surgery: a 1-year randomized, masked, prospective study.

PURPOSE: The authors assess whether adjunctive mitomycin C improves Molteno tube shunt surgery in terms of intraocular pressure (IOP), visual acuity, and complication rates. PATIENTS AND METHODS: Twenty-five eyes of twenty-five consecutive patients undergoing double-plate Molteno implant surgery were randomized to receive either mitomycin C (MMC) 0.4 mg/mL for 2 minutes or a control balanced salt solution in a masked, prospective study. Intraocular pressure, visual acuity, and complications were recorded 1 week and 1, 3, 6, and 12 months after surgery. A repeated measures analysis of variance (ANOVA) model was used to test the overall effect of the drug on IOP and percent change from preoperative IOP. RESULTS: Thirteen eyes received balanced salt solution and 12 eyes received MMC. There was no difference between the groups with respect to age, preoperative IOP, log mean angle of resolution (LogMar) visual acuity, or number of preoperative medications. Except for week 1, there were no differences between the groups at any of the clinic visits with respect to IOP and percent change from baseline IOP. Analysis of the visual acuity (LogMar) showed reduction in vision for both groups. Complications were similar in each group, as were number of postoperative hypotensive agents required. CONCLUSIONS: Adjunct MMC does not demonstrate a significant difference in outcomes compared with placebo in pressure-ridged Molteno implant surgery. Results of this study are limited by a small number of patients in each group and a fixed dose of MMC.

Adult↗
PubMed1997

A glucose-6-phosphate dehydrogenase (G6PD) splice site consensus sequence mutation associated with G6PD enzyme deficiency.

A glucose-6-phosphate dehydrogenase (G6PD) deficient strain of mouse (GPDX) which was developed using the ethylating agent ethylnitrosourea (ENU) has been used to study clonality in epithelial tissues. While the biochemical defect has been quantified, the genetic basis of the deficiency is unknown. The G6PD gene is composed of 13 exons. Exon 1 is not translated, and the ATG start site is near the 5' end of exon 2. Direct sequencing of the exonic regions of the gene from GPDX, C3H, 101, C57BL/6 and BALB/c mice was carried out. The coding region, in which (with a single exception) all mutations found to cause G6PD deficiency in man are situated, showed identical sequences in three of the four strains studied (101 coding region sequence was not examined). However, the G6PD gene in the GPDX mouse showed a single base difference from the other four strains and from the published mouse G6PD sequence (BALB/c) in the 5' splice site consensus sequence at the 3' end of exon 1, part of the untranslated region. The difference was confirmed in four different GPDX mice. This mutation was of the type (A to T transversion) that is known to be induced by ENU; its effect is likely to be exerted through a defect in transcription, splicing or translation, leading to a reduction in protein levels. By Western blot we have found a marked decrease in the G6PD protein levels in the GPDX mouse, with the C3H X GPDX heterozygote showing a lesser decrease. Recently, an increasing number of mutations in the untranslated regions of genes have been found which have effects on protein levels. We believe that the reduced enzyme activity in the GPDX mouse is due to the mutation in the 5' untranslated region (UTR), and that similar mutations may be relevant in other inherited conditions.

Alternative Splicing↗
PubMed1997

Novel method for detection of small amounts of RNA based on the semi-nested polymerase chain reaction.

A technique for the amplification of very small quantities of cDNA based on a semi-nested polymerase chain reaction system has been developed. The technique uses an additional blocking oligonucleotide "primer" in the second round nest which is complementary to one of the first round primers. This prevents amplification of first round product or of any other unwanted products dependent on that primer, but allows amplification of second round product, using first round product as the template. The second round primers are added through the oil layer, eliminating the possibility of introducing first round product aerosol into the atmosphere, as would be the case in a fully nested system. Contamination is therefore minimised, while amplification of the desired product is maximised.

Animals↗
PubMed1996

Behavioral and glucocorticoid responses of adult domestic dogs (Canis familiaris) to companionship and social separation.

Removal of 1 member of a long-standing pair of adult domestic dog (Canis familiaris) kennel mates from the home run for 4 hr had no effect on the behavior or plasma glucocorticoid levels of the remaining dog. When tested in a novel environment, dogs showed increased activity and elevated glucocorticoid levels at the end of the session, but these responses were as large when the dogs were with their kennel mates as when they were alone. However, activity and glucocorticoid levels were not elevated if the dogs were exposed to the novel environment in the presence of their human caretaker. Dogs more often were observed in proximity with, and soliciting social behavior from, the human than the kennel mate. These results highlight the importance of human companionship for the domestic dog and point to a difference in the nature of the social relationships of dogs with humans and with conspecifics.

Animals↗
PubMed1995

Thyroid hormone influences the maturation of apolipoprotein A-I messenger RNA in rat liver.

Chronic administration of thyroid hormone (T3) increases apolipoprotein (apo) A-I gene expression in rat liver. That transcriptional activity of the apoA-I gene is reduced to 50% of control, whereas abundance levels of nuclear and total cellular apoA-I mRNA are increased 3-fold, implies more effective apoA-I mRNA maturation. To study hormonal effects on apoA-I RNA processing, we quantified mRNA precursors in control and T3-treated rats (50 micrograms/100 g body weight for 7 days). Northern blotting, amplification of reverse-transcribed RNA, and ribonuclease protection assays showed that the splicing pathway is branched, in that either intron 1 or intron 2 is removed first from the primary transcript, whereas intron 3 is removed last. In T3-treated rats, abundance levels of the primary transcript, the intron 1-containing precursor devoid of intron 2, the intron 2-containing precursor devoid of intron 1, the intron 3-containing precursor lacking both introns 1 and 2, and nuclear mRNA were 65, 183, 78, 195, and 268% of controls. Compared with control rats, the half-life of the intron 1-containing precursor, measured after injection of actinomycin D, was increased 2-fold in T3-treated rats. In contrast, half-lives of the primary transcript and the intron 2-containing precursor were similar in control and T3-treated rats. Ribonuclease protection assays revealed an RNA species extending from the transcription start site close to the 3' end of intron 1. The abundance of this RNA fragment, probably representing a degradation product, was 2.5-fold higher in control than in T3-treated animals (p < 0.001). Sequences of apoA-I mRNA precursors were identical in control and T3-treated rats which excluded hormonal effects on splice-site selection or post-transcriptional editing of apoA-I transcripts. Compartmental modeling of apoA-I mRNA processing suggested that chronic thyroid hormone administration enhances apoA-I mRNA maturation more than 7-fold by protecting the intron 1-containing precursor devoid of intron 2 from degradation and by facilitating the splicing of intron 1 from this precursor.

Animals↗
PubMed1995

The effects of light, temperature, trance length, and time of day on hypnotic depth.

We evaluated predictions derived from the ultradian theory of hypnosis regarding the effects of temperature, light, trance length, and time of day on reported trance depth in 95 college undergraduates. Temperature and light showed no relation to trance depth. However, as predicted by ultradian theory, subjects who were kept in trance for 15 minutes reported greater trance depth than those who experienced a 5-minute trance. Time of day interacted with subjects' self-reported time of peak alertness in the following way: Subjects who reported greatest alertness in the morning achieved greater trance depth in the morning than in the evening, whereas those subjects who reported greater evening alertness reported deeper trance in the evening than in the morning. This latter finding was inconsistent with ultradian theory and prior research. Alternative explanations for this finding are discussed. Overall, the results from the present study do not provide strong support for Rossi's ultradian theory of hypnosis.

Activity Cycles↗
PubMed1995

Partial or total direct pulmonary venous drainage to right atrium due to malposition of septum primum. Anatomic and echocardiographic findings and surgical treatment: a study based on 36 cases.

The clinical and anatomic findings in 36 patients (21 postmortem cases and 15 living patients) with partially anomalous (16 [44%]) or totally anomalous (20 [56%]) pulmonary venous drainage directly to the right atrium constitute the material basis of this report. Displacement of septum primum--leftward in atrial situs solitus or rightward in atrial situs inversus--was present in all and appeared responsible for the anomalous pulmonary venous drainage. The pulmonary veins were connected with what normally constitutes the posterior wall of the left atrium, which became incorporated into the right atrium because of atrial septal displacement. This abnormality occurred predominantly in patients with visceral heterotaxy, usually with polysplenia, or rarely with asplenia or a normally formed spleen. Poor development or absence of septum secundum appeared responsible for the malposition of septum primum. Echocardiographic recognition of the displacement of septum primum facilitated surgical management.

Abnormalities, Multiple↗
PubMed1995

Thyroid hormone influences conditional transcript elongation of the apolipoprotein A-I gene in rat liver.

Chronic administration of thyroid hormone (T3) increases apoA-I gene expression in rat liver by enhancing mRNA maturation, but reduces apoA-I mRNA synthesis to 50% of control. To gain insight into the inverse relation of mRNA maturation and mRNA synthesis, we measured transcription in livers of control and T3-treated rats (50 micrograms/100 g body weight for 7 days) by nuclear run-on assays using overlapping antisense RNA probes encompassing the apoA-I gene. In control rats, after normalization for hybridization efficiency and probe length, the hybridization signals with intron 3 probes were reduced to 45% of those obtained with exon 1 to exon 3 probes (P < 0.01) indicating transcriptional arrest or pausing close to the exon 3-intron 3 border or 450 to 650 nucleotides downstream of the transcription start site. In T3-treated rats, the elongation block was nearly twice as effective, while the rate of transcription initiation was similar to control. In contrast, the distribution of nascent transcripts across the apoA-IV gene was symmetric, and T3-treatment suppressed apoA-IV mRNA synthesis by processes operating in the 5' region such as transcription initiation. Thus, conditional transcript elongation contributes to the regulation of apoA-I gene expression in rat liver.

Animals↗
PubMed1994

Child dissociation and the family context.

Forty boys and their parents completed measures of dissociation, state anxiety, and perceptions of parental behaviors. Mothers completed a behavior problems checklist about their sons. The results indicated a correspondence between fathers' and sons' dissociation scores. In addition, links were found between parental dissociation, parental inconsistency and rejection, and child dissociation. The findings are discussed in the context of several recently proposed models of the etiology of child dissociative disorders.

Anxiety↗