Biomedical subjects

L Simpson

Publications and source records attributed to L Simpson.

At least 109 records · Page 6Linked to original sources

PubMed1993

Organization of mini-exon and 5S rRNA genes in the kinetoplastid Trypanoplasma borreli.

Mini-exon gene repeats from Trypanoplasma borreli, which belongs to the Cryptobiidae family of the Bodonina suborder of the Kinetoplastida, were isolated by PCR amplification and cloning. The presence of kinetoplastid-like mini-exon genes in T. borreli is consistent with the taxonomic status of this organism as a kinetoplastid protozoan. Two families of repeats were found: 597 nt (T1) and 794 nt (T2), each of which encodes an approximately 95-nt medRNA transcript. The T1 repeats also contain a complete 5S rRNA gene on the complementary strand. The T2 repeats contain a defective copy of a 5S gene, in which the 5' portion is absent. The intergenic regions between the 5'-ends of the mini-exon genes and the 5S rRNA genes in the T1 and T2 repeats are highly diverged. All or most mini-exon genes and 5S genes are located within either the T1 or the T2 repeats. The T1 repeats were localized to a megabase-size chromosome, while the T2 repeats were localized within at least 4 large chromosomes.

Animals↗

PubMed1993

Postpartum abnormalities of carbohydrate and cellular calcium metabolism in pregnancy induced hypertension.

We have previously reported that young, primigravid, African-American women who developed preeclampsia exhibited insulin resistance (elevated fasting insulin:glucose ratios) and abnormal intracellular free calcium ([Ca2+]i) metabolism as early as the second trimester of pregnancy. To determine if these abnormalities persist postpartum (suggesting a genetic link), we evaluated the effects of an oral glucose load (50 g) on plasma and glucose insulin, basal platelet [Ca2+]i and platelet [Ca2+]i responses to arginine vasopressin (AVP). The study population consisted of nine, young, primigravid, African-American women at 43 +/- 12 weeks postpartum from pregnancy induced hypertensive (PIH) gestations and 10 age- and weight-matched African-American women who were 29 +/- 7 weeks postpartum from normal pregnancies. The PIH group consisted of five subjects who were preeclamptic and four subjects with gestational hypertension. Baseline fasting body weights, body mass indices, plasma glucose, plasma insulin, basal platelet [Ca2+]i, and platelet [Ca2+]i responses to AVP were similar in the postpartum PIH and control groups. The oral glucose load had no effect on basal platelet [Ca2+]i levels in either group. However, plasma glucose and insulin and platelet [Ca2+]i responses to AVP were accentuated at 30 min following an oral glucose load suggesting a subtle abnormality of carbohydrate and [Ca2+]i metabolism that persists in individuals with pregnancy induced hypertension. Long term studies involving African-American populations will be necessary to determine if these metabolic abnormalities are associated with an increased propensity to hypertension.

Adolescent↗

PubMed1993

Hyperinsulinemia, insulin resistance, and hyperglycemia: contributing factors in the pathogenesis of hypertension and atherosclerosis.

Subtle abnormalities of carbohydrate metabolism and overt diabetes mellitus are both associated with a substantial increase in the prevalence of hypertension and the accelerated development of atherosclerosis. Hypertension is also a presumed independent risk factor for atherosclerosis, although some of the atherogenic properties of hypertension may be related to the recently recognized subtle metabolic abnormalities commonly found in persons with essential hypertension. The results of epidemiologic studies suggest that the elevated fasting and postprandial insulin levels that often occur in patients with essential hypertension, as well as in patients with type II diabetes mellitus, are an independent risk factor for atherosclerotic cardiovascular disease. Elevated glucose levels in patients with diabetes and hypertension appear to contribute to the acceleration of atherosclerosis, perhaps through toxic effects on the vascular endothelium. Other cardiovascular risk factors that are accentuated in persons with carbohydrate intolerance and hypertension include abnormalities in platelet function, clotting factors, the fibrinolytic system, and dyslipidemia. The goals of both nonpharmacologic and pharmacologic therapy for patients with abnormal carbohydrate metabolism and hypertension are to decrease cardiovascular risk as well as lower blood pressure.

Arteriosclerosis↗

PubMed1993

Patient protocols.

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Clinical Protocols↗

PubMed1993

Detection of Trypanosoma cruzi in blood specimens of chronic chagasic patients by polymerase chain reaction amplification of kinetoplast minicircle DNA: comparison with serology and xenodiagnosis.

A panel of 114 blood samples from chronic chagasic patients and nonchagasic patients was screened for Trypanosoma cruzi by xenodiagnostic, serologic, and polymerase chain reaction (PCR) amplification tests. Blood samples were preserved in a guanidine-EDTA buffer, and total blood DNA was isolated after chemical nuclease cleavage with 1,10-phenanthroline-copper ion and used as a template for PCR amplification of the conserved and variable regions of T. cruzi minicircle molecules. The PCR products were screened by Southern blot hybridization with a digoxigenin-labeled oligonucleotide probe specific for the conserved region of the minicircle. The method showed a sensitivity of 100% compared with the serologic test. In addition, all of the serology-positive, xenodiagnosis-negative samples were positive by PCR. This demonstrates that PCR amplification of T. cruzi kinetoplast minicircle DNA could replace xenodiagnosis for evaluation of parasitemia in chronic chagasic patients and could serve as a complement for serologic testing in the screening of blood bank donors.

Adolescent↗

PubMed1993

Effects of weight reduction on cellular cation metabolism and vascular resistance.

The early stages of weight loss are associated with a reduction in blood pressure, and the mechanisms mediating this reduction remain unclear. Platelet free calcium levels, [Ca2+]i, have been reported to be elevated in essential hypertension and to decrease with pharmacological treatment of the hypertension. In the current study, 18 obese subjects had measurements of blood pressure, forearm blood flow, forearm vascular resistance, and both basal platelet [Ca2+]i and [Ca2+]i responses to vasopressin during 12 weeks on a very low calorie (3,360 kJ, or 800 kcal) diet. Weight reduction was associated with reduction in mean arterial blood pressure at 3-4 weeks. There were associated reductions in forearm vascular resistance and platelet [Ca2+]i as well as increases in forearm blood flow at 3-4 weeks of the diet. Increased forearm blood flow was correlated with weight loss. Vasopressin-induced platelet [Ca2+]i responses increased, which correlated with the reduction in mean arterial pressure at 7-8 weeks of weight loss. Assuming that platelet [Ca2+]i metabolism reflects vascular smooth muscle cell [Ca2+]i metabolism, the data suggest that blood pressure reduction after weight loss may be related to reduced vascular smooth muscle cell [Ca2+]i. The reason for the increased vasopressin-induced [Ca2+]i after weight reduction is unclear.

Adult↗

PubMed1993

Results of directional peripheral atherectomy with reference to histology, histochemistry, and ultrastructure.

One hundred patients with symptomatic peripheral vascular disease were treated with a directional atherectomy catheter; 153 lesions comprising 98 stenoses and 55 occlusions were located in the iliac (n = 22), superficial femoral (n = 114), popliteal (n = 16), and anterior tibial (n = 1) arteries. The majority of these patients were poor candidates for balloon angioplasty because of the complexity of lesions. There were 70 eccentric and 28 concentric lesions and 55 occlusions (mean length 4.2 +/- 2.9 cm). Acute success rate was 94% for both stenoses and occlusions. Four patients were treated in both lower extremities. The stenoses were reduced from 85 +/- 12% to 12 +/- 10% acutely (occlusions 100% to 9 +/- 9%). Six-month angiographic follow-ups were performed in 81% of treated patients, the others refusing angiography. Mean stenosis after six months was 33 +/- 25% (occlusions 44 +/- 28%). Restenosis (> 50%) was found in 20% of treated lesions: 26% in concentric lesions, 8% in eccentric lesions, and 32% in occluded vessels. Treatment of peripheral vascular disease with the atherectomy device is safe and effective therapy with good long-term results. These results were obtained in complex lesions with 55 occlusions. Atherectomy seems to be particularly beneficial in the treatment of eccentric and complex stenoses and is not limited by occlusion or calcification. Furthermore, insight into the pathogenesis of arteriosclerosis and the development of restenosis is enabled by analysis of removed plaque material.

Aged↗

PubMed1993

Effects of three colors in an office interior on mood and performance.

This study examined the effects of three hues on subjects' performance and mood while in an office work environment for 1 hour. Pretest/posttest measurements were completed. Work performance was measured using words typed, typing errors, and a ratio of errors to words typed. Anxiety, depression, and arousal were measured by the Eight State Questionnaire of Curran and Cattell. A total of 45 women, ages 18 to 24 years, were tested individually in a single office space: 15 when the office walls were painted red/warm, 15 when walls were blue-green/cool, and 15 when walls were white/neutral. Analysis of covariance of posttest measurements with the pretest as a covariate showed no significant differences among the three groups on performance or scores on anxiety, depression, and arousal. If color of the environment has an effect on work performance or mood, either the effect was too small to be detected with samples of 15 subjects or longer participation than one hour was required.

Adult↗

PubMed1992

Formation of guide RNA/messenger RNA chimeric molecules in vitro, the initial step of RNA editing, is dependent on an anchor sequence.

Synthetic pre-edited messenger RNA (mRNA) and guide RNA (gRNA) for the 5'-edited maxicircle-encoded ND7 cryptogene from Leishmania tarentolae formed chimeric molecules upon incubation in the presence of a mitochondrial extract. These chimeric molecules consisted of the gRNAs covalently linked to the mRNAs by short oligo(U) tails at normal editing sites in most cases. Unlike the previously reported chimeras present in steady-state kinetoplast RNA, the in vitro-synthesized chimeras showed no editing of downstream editing sites. The synthesis of chimeric RNAs required ATP and was dependent on the formation of a gRNA/mRNA anchor duplex 3' of the pre-edited region, as shown by in vitro mutagenesis of the mRNA and the gRNA. mRNA sequences 3' and 5' of the pre-edited region also affected the efficiency of the chimera-forming activity. This in vitro system may accurately represent the initial step in RNA editing.

Animals↗

PubMed1992

The polarity of editing within a multiple gRNA-mediated domain is due to formation of anchors for upstream gRNAs by downstream editing.

Seventeen kinetoplast minicircle-encoded and nine maxicircle-encoded gRNA genes have been identified. Six overlapping minicircle-encoded gRNAs mediate editing for the 5'-pan-edited MURF4 gene and two for the 5'-edited COIII gene. The pan-edited RPS12 mRNA is edited by seven minicircle-encoded gRNAs and one maxicircle-encoded gRNA. The 3'-most gRNA in each domain forms an anchor with unedited mRNA, whereas upstream gRNAs form anchors only with edited mRNA, thereby explaining the observed 3' to 5' polarity of editing within an editing domain. We suggest that a role of G-U base pairs is to allow breathing of the edited mRNA-gRNA hybrid and formation of the upstream anchor hybrid.

Animals↗

PubMed1992

Generation of unexpected editing patterns in Leishmania tarentolae mitochondrial mRNAs: misediting produced by misguiding.

We have analyzed the generation of unexpected patterns of RNA editing, i.e., those not following a strict 3' to 5' progression, which occur in junction regions between fully edited and preedited sequences. Evidence is presented that these patterns are generated by misediting due to specific events of misguiding. Misediting can occur through the interaction of inappropriate gRNAs with mRNAs or appropriate gRNAs in an incorrect fashion. Four possible mechanisms for the generation of misedited sequences are presented. Chimeric molecules have been detected in steady-state mitochondrial RNAs that are composed of misguiding gRNAs covalently linked to mRNAs at misediting sites by the 3' oligo(U) tail. We propose that misediting within junction regions can be corrected by appropriately acting gRNAs.

Animals↗

PubMed1992

Computer methods for locating kinetoplastid cryptogenes.

RNA editing in the mitochondria of kinetoplastid protoza involves the insertion and/or deletion of precise numbers of uridine residues at precise locations in the numbers of uridine residues at precise locations in the transcribed RNA of certain genes. These genes are known as cryptogenes. In this paper we study computational algorithms to search for unknown cryptogenes and for the associated templates for insertion of uridines, gRNA sequences. The pairwise similarity search algorithm of Smith and Waterman (1) is modified to study this problem. The algorithm searches for unknown gRNAs given the cryptogene sequence. The method is tested on 4 known cryptogenes from L.tarentolae which are known to have 7 associated gRNAs. The statistical distribution of the longest gRNA when comparing random sequences is derived. Finally we develop an algorithm to search for cryptogenes using amino acid sequences from related proteins.

Algorithms↗

PubMed1992

A ribonuclease activity is activated by heparin or by digestion with proteinase K in mitochondrial extracts of Leishmania tarentolae.

A ribonuclease activity in a 100,000 x g supernatant of a Triton lysate of a mitochondrial-kinetoplast fraction from Leishmania tarentolae is activated by incubation with heparin or by predigestion of the lysate with proteinase k or pronase. In vitro-transcribed pre-edited cytochrome b mRNA is cleaved at several sites. With time, complete degradation of the RNA occurs. All cleavages occurred within putative single-stranded regions of the RNA. No cleavage was observed with 9 S rRNA. The presence of a nonspecific nucleotide or nucleoside slows the rate of cleavage. The cleavage activity is inhibited by sodium dodecyl sulfate or phenol/chloroform extraction, is retained by a 10-kDa cutoff filter, and passes through a 30-kDa filter. Micrococcal nuclease inhibits the proteinase-induced activity but not the heparin-induced activity.

Animals↗

PubMed1992

Efficacy of directional coronary atherectomy in cases unsuitable for percutaneous transluminal coronary angioplasty (PTCA) and after unsuccessful PTCA.

Directional coronary atherectomy (DCA) was used in 10 female and 50 male patients with an average age of 58 years. They were categorized into three different groups depending on the indications for atherectomy. Group 1 included all patients who had atherectomy as their primary intervention (n = 20) because they were assumed to be unsuitable for percutaneous transluminal coronary angioplasty (PTCA). Group 2 consisted of patients in whom DCA was used after failed balloon dilatation with unsuccessful but uneventful treatment (n = 17). Group 3 (n = 23) included patients in whom DCA was performed as a "rescue" or "bailout" procedure after unsuccessful PTCA resulting in critical ischemia (ECG changes, chest pain, hypotension, and shock). The target lesions were located in the left main artery in two, left anterior descending artery in 43, right coronary artery in 15, and aortocoronary venous bypass in five. The mean length of the lesions was 8 mm (2 to 25 mm). The overall success rate for 65 lesions was 92%. The mean stenosis was reduced from 87 +/- 12% to 19 +/- 17% in patients with primary success. Presently available follow-up angiograms (30) showed six restenoses. Major complications occurred in seven patients (myocardial infarction in two and coronary artery bypass graft surgery within 24 hours in five); there were no deaths. Our results show that DCA is a safe and effective technique that can extend the use of percutaneous procedures and provide a promising nonsurgical option in cases of unsuccessful PTCA.

Angioplasty, Balloon, Coronary↗

PubMed1992

Recurrent polymorphisms in small chromosomes of Leishmania tarentolae after nutrient stress or subcloning.

Molecular karyotypes of the UC, LEM87 and LEM115 Leishmania tarentolae strains were obtained. All strains had 24-28 chromosomal bands which varied in size between 300 kb and 2.9 Mb. Several recurrent chromosomal polymorphisms occurred in LEM115 after nutrient shock or subcloning. One type of polymorphism involves the truncation of a 365-kb chromosome which contains the miniexon genes. This specific chromosome breakage appears to be induced by the nutrient shock or subcloning process and also occurs spontaneously during routine passage. Another polymorphism is the appearance of a 90-kb minichromosome (115-SNA1) after severe nutrient shock. This appears to be selection of a pre-existing cell type from a mosaic population. The 115-SNA1 minichromosome has sequence homology with a minichromosome in LEM87 cells but shows no homology with any chromosomes in 115wt or other strains. The copy number of 115-SNA1 varies with culture conditions, suggesting a relaxed centromeric control. The nature and origin of this minichromosome is not known.

Animals↗

PubMed1992

Rotational angioplasty and directional atherectomy to treat complex lesions of the right coronary artery.

A combination of interventional devices including the Rotablator and directional coronary atherectomy (DCA) was used to treat a 39-year-old patient with a complex lesion of the right coronary artery. The devices enabled the recanalization and reconstruction of the diseased vessel without laceration or dissection, leaving a smooth-edged segment. The histological analysis of the tissue obtained from DCA revealed no predictors of restenosis, like highly cellular material or media. Thus, combination of mechanical interventional devices allowed to treat a highly complex lesion without lacerating the vessel and leaving an excellent acute and long-term outcome.

Adult↗

PubMed1992

An intergenic G-rich region in Leishmania tarentolae kinetoplast maxicircle DNA is a pan-edited cryptogene encoding ribosomal protein S12.

Six short G-rich intergenic regions in the maxicircle of Leishmania tarentolae are conserved in location and polarity in two other kinetoplastid species. We show here that G-rich region 6 (G6) represents a pan-edited cryptogene which contains at least two domains edited independently in a 3'-to-5' manner connected by short unedited regions. In the completely edited RNA, 117 uridines are added at 49 sites and 32 uridines are deleted at 13 sites, creating a translated 85-amino-acid polypeptide. Similar polypeptides are probably encoded by pan-edited G6 transcripts in two other species. The G6 polypeptide has significant sequence similarity to the family of S12 ribosomal proteins. A minicircle-encoded gRNA overlaps 12 editing sites in G6 mRNA, and chimeric gRNA/mRNA molecules were shown to exist, in agreement with the transesterification model for editing.

Amino Acid Sequence↗

PubMed1992

Hypertension in insulin-resistant Zucker obese rats is independent of sympathetic neural support.

We have previously reported that insulin-resistant Zucker obese rats exhibit hypertension associated with impaired vascular smooth muscle (VSM) Ca2+ transport and proposed that this results from failure of insulin to regulate VSM Ca2+ transport in insulin resistance. However, hypertension in insulin-resistant states is generally attributed to hyperinsulinemia, with a consequent stimulation of sympathetic neural activity. Accordingly, the present study was conducted to determine whether the hypertension observed in Zucker obese rats compared with their lean controls was dependent on either increased sympathetic neural activity or exaggerated vascular reactivity. Intra-arterial blood pressure responses to ganglionic blockade with Ecolid (chlorisondamine chloride) and to graded intravenous injections of angiotensin II and norepinephrine were compared in 6- to 8-wk-old male Zucker rats and their lean controls (n = 10/group). The obese rats exhibited significant hypertension before ganglionic blockade (P less than 0.001), and this difference was largely sustained during ganglionic blockade (P less than 0.005). Furthermore, the obese rats exhibited greater pressor sensitivity to both angiotensin II and to norepinephrine during ganglionic blockade (P less than 0.01). Thus enhanced pressor sensitivity, independent of sympathetic neural activity, appears to support hypertension in Zucker obese rats.

Angiotensin II↗