Biomedical subjects

M J Simmons

Publications and source records attributed to M J Simmons.

At least 19 recordsLinked to original sources

PubMed2005

Constitutive proteasome-mediated turnover of Bfl-1/A1 and its processing in response to TNF receptor activation in FL5.12 pro-B cells convert it into a prodeath factor.

Bfl-1/A1 is generally recognized as a Bcl-2-related inhibitor of apoptosis. We show that Bfl-1 undergoes constitutive ubiquitin/proteasome-mediated turnover. Moreover, while Bfl-1 suppresses apoptosis induced by staurosporine or cytokine withdrawal, it is proapoptotic in response to tumor necrosis factor (TNF) receptor activation in FL5.12 pro-B cells. Its anti- versus proapoptotic effect is regulated by two proteolytic events: (1) its constitutive proteasome-mediated turnover and (2) its TNF/cycloheximide (CHX)-induced cleavage by mu-calpain, or a calpain-like activity, coincident with acquisition of a proapoptotic phenotype. In vitro studies suggest that calpain-mediated cleavage of Bfl-1 occurs between its Bcl-2 homology (BH)4 and BH3 domains. This would be consistent with the generation of a proapoptotic Bax-like BH1-3 molecule. Overall, our studies uncovered two new regulatory mechanisms that play a decisive role in determining Bfl-1's prosurvival versus prodeath activities. These findings might provide important clues to counteract chemoresistance in tumor cells that highly express Bfl-1.

Amino Acid Sequence↗

PubMed2001

Is a palpable short saphenous vein a useful clinical sign in varicose vein assessment?

The short saphenous vein (SSV) may be palpable in the popliteal fossa in patients with varicose veins. A prospective study has been carried out to determine the significance of this sign in the presence of primary varicose veins. The SSV was assessed by palpation of the popliteal fossa with the knee slightly flexed. Hand-held Doppler insonation (HHD) was also used in the out-patient clinic. All patients had SSV assessment by duplex scanning. One hundred and sixty legs were examined. In 68 the SSV was palpable; 39 (57%) of these had SSV reflux on duplex examination. When the SSV was not palpable (92 legs), only 1% (1 leg) refluxed on duplex scanning. SSV palpability had a 98% sensitivity, 75% specificity, 57% positive predictive value (PPV), and 99% negative predictive value (NPV). In comparison, HHD had 80% sensitivity, 87% specificity, 67% PPV and 93% NPV. The combined tests had 78% sensitivity, 73% specificity, 76% PPV and 100% NPV. Palpation of the SSV is a valuable part of clinical examination. If the SSV is not palpable, it is unlikely to reflux.

Adult↗

PubMed2000

Maintenance of patency following remote superficial femoral artery endarterectomy.

BACKGROUND: Remote superficial femoral artery endarterectomy (RSFE) is a minimally invasive means of superficial femoral artery revascularisation. It comprises a single groin incision and securing of the distal cut end of atheroma with an intraluminal stent. AIM: To determine medium-term results of RSFE, with particular reference to costs of maintaining patency. METHODS: Stenosis development, and patency of 25 RSFE were compared with 25 randomly selected in situ vein bypasses with similar follow-up (18-33 months). RESULTS: Following RSFE 17 stenoses were identified by duplex surveillance. Half of those arteries patent at 1 yr had stenoses. Angioplasty (PTA) was carried out for 11 stenoses. Four stenoses developed more than 12 months following RSFE. One patient died and nine arteries occluded during follow-up. Primary and primary- assisted patency at 18 months were 31 and 63% respectively. By contrast six stenoses were identified in 25 in situ grafts, all within one year. Four PTAs were carried out. Three grafts occluded. Excluding cost of three monthly duplex surveillance the cost of maintaining RSFE patency was approximately five times that of maintaining in situ bypass patency. CONCLUSION: The initial cost advantage of RSFE is offset by the increased costs of maintaining patency. Duplex surveillance probably needs to be continued indefinitely.

Aged↗

PubMed2000

Carotid duplex imaging: variation and validation.

BACKGROUND: Duplex imaging is increasingly used as the only investigation before carotid endarterectomy, but many different criteria exist in the literature for the detection of a severe (70-99 per cent) carotid stenosis. This study aimed to investigate current practice in carotid duplex imaging in Great Britain and Ireland. METHODS: A postal questionnaire was sent to 86 vascular surgical units. RESULTS: The median number of scans performed per year was 450 (range 60-4500). Thirty-six per cent of units who responded used peak systolic : end diastolic velocity ratio to calculate carotid stenosis. Overall, nine different major duplex criteria were used to grade carotid stenosis in 14 different systems of percentage bands. Only 51 per cent of units verified their duplex criteria against angiography. Eighteen per cent of units used two or more different types of duplex scanner and applied the same diagnostic criteria to each machine. CONCLUSION: A wide variation in diagnostic duplex criteria and methods of grading stenosis exists among vascular units. Internal validation is not performed routinely. Standardization of duplex criteria would ensure greater consistency, but would not replace the need for validation of results within each unit.

Carotid Artery, Internal↗

PubMed2000

Remote superficial femoral artery endarterectomy: medium-term results.

BACKGROUND: the aim of this study is to determine the medium-term results following successful remote superficial-femoral endarterectomy (RSFE). SETTING: district general hospital in United Kingdom. METHODS: RSFE comprises a single incision over the origin of the superficial femoral artery. The endarterectomy is carried out in a closed fashion from above. The cut end of distal atheroma is secured with a stent. Twenty-five limbs were followed up with three monthly duplex scans and angiography if any abnormality was suggested. All patients presented with intermittent claudication; in addition three had rest pain and three ulceration or gangrene. The length of atheromatous core removed was 10-30 cm. RESULTS: all patients had a follow-up of at least one year (range 12-27 months). Eleven arteries developed 14 stenoses. Nine became apparent within nine months of RSFE. The cumulative risk of stenoses developing in patent arteries was 24% at 6 and 63% at 12 months. Eleven angioplasties (PTA) of these stenoses were undertaken. Nine of these remain patent at a median of 12 months after PTA. At one year primary patency was 10 of 25 (40%), primary-assisted patency 18 of 25 (72%) and secondary patency 19 of 25 (76%) and at two years 29%, 57% and 57% respectively. CONCLUSIONS: RSFE is worth considering for superficial femoral artery occlusive disease, particularly in high-risk patients without suitable vein and with limited life expectancy. Careful duplex surveillance is important. Until stenoses can be prevented, the widespread use of RSFE cannot be recommended.

Aged↗

PubMed1996

Repression of hybrid dysgenesis in Drosophila melanogaster by heat-shock-inducible sense and antisense P-element constructs.

Sets of sense and antisense P-element constructs controlled by a heat-shock-inducible promoter were tested for their ability to repress manifestations of P-element activity in vivo. As a group, the antisense constructs repressed pupal lethality, a somatic manifestation of P activity, and this repression was significantly enhanced by heat shock. Three of the 11 antisense constructs also repressed gonadal dysgenesis, a manifestation of P activity in the female germ line; however, none had any effect on P-element-mediated mutability in the male germ line. Among the 13 different heat-shock-inducible sense constructs that were tested, those containing the KP and DP elements were strong repressors of pupal lethality, gonadal dysgenesis and P-element-mediated mutability; however, individual lines carrying these constructs varied in their ability to repress each of these traits, presumably because of genomic position effects. With the exception of the sense construct that contained a complete P element, none of the sense or antisense constructs repressed a lacZ reporter gene driven by the P-element promoter. Overall, the experimental results suggest that in nature, P-element activity could be regulated by P-encoded polypeptides and by antisense P RNAs.

Animals↗

PubMed1996

Effects of stapedial arch fractures on conductive hearing loss and stapedial reflexes.

OBJECTIVE: It has been stated in the clinical literature that stapedial fractures could produce a significant conductive hearing loss while leaving the contralateral stapedial reflex intact. The objective of this study is to test this hypothesis in an animal model. DESIGN: Nine hooded rats underwent acoustic-stapedial reflex (ASR) and cochlear microphonic (CM) threshold determinations before and after middle ear surgery. An argon laser was used to divide the tensor tympani tendon, the anterior stapedial curs, and the posterior stapedial crus, sequentially. The initial functional measures were repeated after each laser procedure to document its effect. RESULTS: Dividing the tensor tympani tendon and the anterior stapedial crus had variable and small effects on ASR and CM thresholds. Division of the second (posterior) crus eliminated stapedial reflexes and produced a significant hearing loss. CONCLUSIONS: This study refutes the hypothesis that fracture of one (anterior) stapedial crus will significantly alter ossicular sound transmission, but it supports the hypothesis that measured stapedial reflexes would not be significantly altered by a single crus fracture. Therefore, the surgeon exploring an ear for a conductive hearing loss with an intact contralateral stapedial reflex should look carefully for another source of the hearing loss if finding only a single stapedial arch fracture.

Animals↗

PubMed1995

S elements: a family of Tc1-like transposons in the genome of Drosophila melanogaster.

The S elements form a diverse family of long-inverted-repeat transposons within the genome of Drosophila melanogaster. These elements vary in size and sequence, the longest consisting of 1736 bp with 234-bp inverted terminal repeats. The longest open reading frame in an intact S element could encode a 345-amino acid polypeptide. This polypeptide is homologous to the transposases of the mariner-Tc1 superfamily of transposable elements. S elements are ubiquitous in D. melanogaster populations and also appear to be present in the genomes of two sibling species; however, they seem to be absent from 17 other Drosophila species that were examined. Within D. melanogaster strains, there are, on average, 37.4 cytologically detectable S elements per diploid genome. These elements are scattered throughout the chromosomes, but several sites in both the euchromatin and beta heterochromatin are consistently occupied. The discovery of an S-element-insertion mutation and a reversion of this mutation indicates that S elements are at least occasionally mobile in the D. melanogaster genome. These elements seem to insert at an AT dinucleotide within a short palindrome and apparently duplicate that dinucleotide upon insertion.

Amino Acid Sequence↗

PubMed1994

Gross chromosome rearrangements mediated by transposable elements in Drosophila melanogaster.

A combination of cytogenetic and molecular analyses has shown that several different transposable elements are involved in the restructuring of Drosophila chromosomes. Two kinds of elements, P and hobo, are especially prone to induce chromosome rearrangements. The mechanistic details of this process are unclear, but, at least some of the time, it seems to involve ectopic recombination between elements inserted at different chromosomal sites; the available data suggest that these ectopic recombination events are much more likely to occur between elements in the same chromosome than between elements in different chromosomes. Other Drosophila transposons also appear to mediate chromosome restructuring by ectopic recombination; these include the retrotransposons BEL, roo, Doc and I and the foldback element FB. In addition, two retrotransposons, HeT-A and TART, have been found to be associated specifically with the ends of Drosophila chromosomes. Very limited data indicate that transposon-mediated chromosome restructuring is occurring in natural populations of Drosophila. This suggests that transposable elements may help to shape the structure of the Drosophila genome and implies that they may have a similar role in other organisms.

Animals↗

PubMed1994

An epidemiologic study of maxillofacial trauma at University Medical Center in Lafayette, a regional referral center.

The authors retrospectively reviewed maxillofacial trauma admissions at University Medical Center in Lafayette, Louisiana, a Level II trauma center, over the 2-year period from July 1, 1990 to June 30, 1992. This study encompassed 208 fractures in 166 patients. All patients in this study group required surgical intervention for their maxillofacial injury. Variables examined in this cohort included age, race, gender, seasonal variation, fracture location, mechanism of injury, associated injuries, seatbelt utilization, substance abuse, surgical management, complications, operative duration, hospital stay, hour of presentation, and preoperative imaging modalities. The purpose of our study is to provide an epidemiologic review of maxillofacial trauma in the Acadian community of southwestern Louisiana.

Academic Medical Centers↗

PubMed1993

Genetic instability in Drosophila melanogaster mediated by hobo transposable elements.

Eight independent recessive lethal mutations that occurred on derivatives of an unstable X chromosome (Uc) in Drosophila melanogaster were analyzed by a combination of genetic and molecular techniques. Seven of the mutations were localized to complementation groups in polytene chromosome bands 6E; 7A. In situ hybridization and genomic Southern analysis established that hobo transposable elements were associated with all seven of the mutations. Six mutations involved deletions of DNA, some of which were large enough to be seen cytologically, and in each case, a hobo element was inserted at the junction of the deletion's breakpoints. A seventh mutation was associated with a small inversion between 6F and 7A-B and a hobo element was inserted at one of its breakpoints. One of the mutant chromosomes had an active hobo-mediated instability, manifested by the recurrent production of mutations of the carmine (cm) locus in bands 6E5-6. This instability persisted for many generations in several sublines of an inbred stock. Two levels of instability, high and basal, were distinguished. Sublines with high instability had two hobo elements in the 6E-F region and produced cm mutations by deleting the segment between the two hobos; a single hobo element remained at the junction of the deletion breakpoints. Sublines with low instability had only one hobo element in the 6E-F region, but they also produced deletion mutations of cm. Both types of sublines also acquired hobo-mediated inversions on the X chromosome. Collectively, these results suggest that interactions between hobo elements are responsible for the instability of Uc. It is proposed that interactions between widely separated elements produce gross rearrangements that restructure the chromosome and that interactions between nearby elements cause regional instabilities manifested by the recurrence of specific mutations. These regional instabilities may arise when a copy of hobo transposes a short distance, creating a pair of hobos that can interact to produce small rearrangements.

Animals↗

PubMed1993

Repression of hybrid dysgenesis in Drosophila melanogaster by individual naturally occurring P elements.

Individual P elements that were genetically isolated from wild-type strains were tested for their abilities to repress two aspects of hybrid dysgenesis: gonadal dysgenesis and mutability of a double-P element-insertion allele of the singed locus (snw). These elements were also characterized by Southern blotting, polymerase chain reaction amplification and DNA sequencing. Three of the elements were 1.1-kb KP elements, one was a 1.2-kb element called D50, and one was a 0.5-kb element called SP. These three types of elements could encode polypeptides of 207, 204, and 14 amino acids, respectively. Gonadal dysgenesis was repressed by two of the KP elements (denoted KP(1) and KP(6)) and by SP, but not by the third KP element (KP(D)), nor by D50. Repression of gonadal dysgenesis was mediated by a maternal effect, or by a combination of zygotic and maternal effects generated by the P elements themselves. The mutability of snw was repressed by the KP(1) and KP(6) elements, by D50 and by SP, but not by KP(D); however, the SP element repressed snw mutability only when the transposase came from complete P elements and the D50 element repressed it only when the transposase came from the modified P element known as delta 2-3. In all cases, repression of snw mutability appeared to be mediated by a zygotic effect of the isolated P element. Each of the isolated elements was also tested for its ability to suppress the phenotype of a P-insertion mutation of the vestigial locus (vg21-3). D50 was a moderate suppressor whereas SP and the three KP elements had little or no effect. These results indicate that each isolated P element had its own profile of repression and suppression abilities. It is suggested that these abilities may be mediated by P-encoded polypeptides or by antisense P RNAs initiated from external genomic promoters.

Alleles↗

PubMed1992

Mechanism of differential inhibition of lactate dehydrogenase isoenzymes in the BMC LD-1 assay.

The mechanism of inhibition of lactate dehydrogenase (LD) isoenzymes by guanidinium thiocyanate (GSCN) used in the LD-1 assay developed by Boehringer Mannheim Corporation (BMC) was investigated. Michaelis-Menten inhibition kinetics for the individual isoenzymes revealed that GSCN competitively inhibited LD-1 in the presence of lactate and NAD+, but is a noncompetitive inhibitor of LD-5. LD-2 and LD-3 exhibited mixed inhibition kinetics. The inhibition constants were two- to threefold smaller for LD-5 than for LD-1. Time-dependent studies also showed that the isoenzymes underwent a different rate of inactivation by GSCN. LD-5, LD-3, and LD-2 were rapidly inactivated within 1 min under the BMC assay conditions, whereas LD-1 lost only about 20% of activity after 10 min. The presence of lactate further protects LD-1, but not other isoenzymes. Under this condition, LD-1 was not inactivated during the initial 6 min of reaction. Separate experiments demonstrated that both guanidinium and thiocyanate ions are responsible for the inactivation process that was found to be irreversible. We speculate that GSCN selectively denatures the M subunit of LD. The H subunit is less susceptible to denaturation and is further stabilized by lactate.

Guanidines↗

PubMed1992

Double blind comparison of Iomeprol 350 and Iopamidol 340 in intravenous digital subtraction angiography for peripheral vascular disease.

A randomized double blind study was undertaken to compare the diagnostic efficacy and side effects of a new non-ionic contrast medium Iomeprol with a commonly used one--Iopamidol. Visual and densitometric comparison was made of intravenous digital subtraction angiograms performed for peripheral vascular disease. The results show the two media to be similar both in imaging quality and in the incidence of associated side effects. Ninety-eight per cent of the intravenous digital subtraction angiograms were assessed as adequate for clinical management by the vascular surgeon.

Adult↗

PubMed1991

Prevalence of abdominal aortic aneurysm in patients with occlusive peripheral vascular disease.

Over a 1-year period, 242 patients with peripheral vascular disease underwent abdominal ultrasonography to detect the presence of an abdominal aortic aneurysm. In 34 (14 per cent) an abdominal aortic aneurysm was found; half of these aneurysms were greater than 4 cm in diameter. In addition, 16 patients had ectatic aortas. Abdominal aortic aneurysms were more common in men than in women (17 versus 8 per cent). Patients with claudication were as likely to have an abdominal aortic aneurysm as those with rest pain or gangrene. The presence of aortoiliac occlusive disease increased the chance of an aneurysm being present (P less than 0.02). Patients with occlusive peripheral vascular disease are a high-risk group with regard to the development of an abdominal aortic aneurysm. Patients with proximal occlusive disease represent a subgroup at even higher risk.

Adult↗

PubMed1991

Genetic and molecular analysis of repression in the P-M system of hybrid dysgenesis in Drosophila melanogaster.

Twelve inbred lines derived from an M' strain of Drosophila melanogaster were used to study the repression of P-element-mediated hybrid dysgenesis. Initial assessments indicated that the lines differed in the ability to repress gonadal dysgenesis, and that this ability was highly correlated with the ability to repress snw hypermutability. Later assessments indicated that most of the lines with low or intermediate repression potential evolved to a state of higher repression potential; however, Southern analyses failed to reveal significant changes in the array of genomic P elements that could account for this evolution. In addition, none of the lines possessed the incomplete P element known as KP, which has been proposed to explain repression in some D. melanogaster strains. One of the lines maintained intermediate repression potential throughout the period of study (52 generations), indicating that the intermediate condition was not intrinsically unstable. Genetic analyses demonstrated that in some of the lines, repression potential was influenced by factors that were inherited maternally through at least two generations; however, these factors were not as influential as those in a classic P cytotype strain. Additional tests with a dysgenesis-inducing X chromosome called T-5 indicated that repression itself was mediated by a combination of maternal effects and paternally inherited factors that were expressed after fertilization. These tests also suggested that in some circumstances, the P transposase, or its message, might be transmitted through the maternal cytoplasm.

Animals↗

PubMed1991

Inheritance of P-element regulation in Drosophila melanogaster.

The ability to repress P-element-induced gonadal dysgenesis was studied in 14 wild-type strains of D. melanogaster derived from populations in the central and eastern United States. Females from each of these strains had a high ability to repress gonadal dysgenesis in their daughters. Reciprocal hybrids produced by crossing each of the wild-type strains with an M strain demonstrated that repression ability was determined by a complex mixture of chromosomal and cytoplasmic factors. Cytoplasmic transmission of repression ability was observed in all 14 strains and chromosomal transmission was observed in 12 of them. Genomic Southern blots indicated that four of the strains possessed a particular type of P element, called KP, which has been proposed to account for the chromosomal transmission of repression ability. However, in this study several of the strains that lacked KP elements exhibited as much chromosomal transmission of repression ability as the strains that had KP elements, suggesting that other kinds of P elements may be involved.

Animals↗

PubMed1990

Quantitative effects of P elements on hybrid dysgenesis in Drosophila melanogaster.

Genetic analyses involving chromosomes from seven inbred lines derived from a single M' strain were used to study the quantitative relationships between the incidence and severity of P-M hybrid dysgenesis and the number of genomic P elements. In four separate analyses, the mutability of snw, a P element-insertion mutation of the X-linked singed locus, was found to be inversely related to the number of autosomal P elements. Since snw mutability is caused by the action of the P transposase, this finding supports the hypothesis that genomic P elements titrate the transposase present within a cell. Other analyses demonstrated that autosomal transmission ratios were distorted by P element action. In these analyses, the amount of distortion against an autosome increased more or less linearly with the number of P elements carried by the autosome. Additional analyses showed that the magnitude of this distortion was reduced when a second P element-containing autosome was present in the genome. This reduction could adequately be explained by transposase titration; there was no evidence that it was due to repressor molecules binding to P elements and inhibiting their movement. The influence of genomic P elements on the incidence of gonadal dysgenesis was also investigated. Although no simple relationship between the number of P elements and the incidence of the trait could be discerned, it was clear that even a small number of elements could increase the incidence markedly. The failure to find a quantitative relationship between P element number and the incidence of gonadal dysgenesis probably reflects the complex etiology of this trait.

Animals↗