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At least 109 records · Page 6Linked to original sources
PubMed1994

Functional analysis of transcription of the Mycobacterium tuberculosis 16S rDNA-encoding gene.

A functional analysis of Mycobacterium tuberculosis 16S ribosomal RNA (rRNA) transcription and processing was undertaken in this study. RNA:DNA hybridizations indicated that the maximum transcriptional activity of rRNA-encoding genes (rDNA) corresponded to the earliest period of exponential growth. Transcription start points (tsp) were mapped by primer extension analysis of RNA from M. tuberculosis H37Rv and M. tuberculosis H37Ra. An identical pattern of rRNA transcription and processing was exhibited in laboratory-grown cultures of M. tuberculosis H37Rv and H37Ra. One promoter represents the structural equivalent of the Escherichia coli rrn P2 promoter. The precursor transcripts are processed into mature 16S rRNA through a pathway that includes recognition of RNA secondary structure by ribonuclease III (RNase III) in the stem structure surrounding the 16S rRNA indicating that at least this RNA processing step is conserved in mycobacteria and E. coli. The 16S rDNA promoter region from H37Rv was cloned upstream from the promoterless chloramphenicol (Cm) acetyltransferase (CAT)-encoding gene (cat) in a shuttle plasmid vector, pSD7. The promoter-fusion construct, pSD7.16S, was characterized by CAT assays, measurement of percent survival in Cm-containing medium and in vivo transcription analysis in M. smegmatis. The M. smegmatis transformant exhibited a CAT activity of 16,669 nmol/min per mg protein, suggesting that the 16S promoter was of exceptionally high strength. Two tsp utilized in M. tuberculosis were also employed in M. smegmatis. The cat mRNA synthesized under the direction of the ribosomal promoter was less stable, as compared to genome-derived rRNA.

Base Sequence↗
PubMed1989

A comparison of dummy variable versus traditional multiple discriminant function analysis.

The authors compare the use of dummy variable and traditional multiple discriminant function analysis when dealing with research questions where ratio or nominal scale independent variables can be used. A healthcare-related example of using dv MDF is given and the authors conclude that it is superior to traditional MDF for determining variable importance and developing market segment profiles.

Analysis of Variance↗
PubMed1984

[Importance of a structural and functional analysis of the fallopian epithelium in tubal pregnancy and endometrial adenocarcinoma].

The structural-functional analysis of the uterine tube epithelium is proposed as an additional indirect index of the ovarian hormonal activity. Several standard types of the tubal epithelium are distinguished (proliferative, secretory, gravidal, non-functional, proliferative-hyperplastic) which are characteristic of certain level of various sex hormones in the woman organism. The control data obtained are used for the evaluation of the hormonal background in women with tubal pregnancy and endometrial carcinoma. The signs of ovarian dysfunction were observed in 55.2 and 43.3% of cases respectively and these symptoms were reflected in the pathogenesis and clinical picture of the diseases studied.

Adenocarcinoma↗
PubMed1998

Cloning and functional analysis of human p51, which structurally and functionally resembles p53.

The p53 tumor suppressor gene, which is induced by DNA damage and/or stress stimuli, causes cells to undergo G1-arrest or apoptotic death; thus it plays an essential role in human carcinogenesis. We have searched for p53-related genes by using degenerate PCR, and have identified two cDNA fragments similar to but distinct from p53: one previously reported, p73, and the other new. We cloned two major splicing variants of the latter gene and named these p51A and p51B (a human homologue of rat Ket). The p51A gene encodes a 448-amino-acid protein with a molecular weight of 50.9 kDa; and p51B, a 641-amino-acid protein with a molecular weight of 71.9 kDa. In contrast with the ubiquitous expression of p53, expression of p51 mRNA was found in a limited number of tissues, including skeletal muscle, placenta, mammary gland, prostate, trachea, thymus, salivary gland, uterus, heart and lung. In p53-deficient cells, p51A induced growth-suppression and apoptosis, and upregulated p21waf-1 through p53 regulatory elements. Mutations in p51 were found in some human epidermal tumors.

Alternative Splicing↗
PubMed1998

The effect of reinforcer preference on functional analysis outcomes.

We combined functional analyses and concurrent-schedule assessments to identify reinforcer preference during situations in which problem behavior may have been multiply controlled. Participants were 3 children with developmental delays who engaged in problem behavior during toy play with another child and one adult present, suggesting that problem behavior may have been maintained by adult attention or access to tangible reinforcement. Thus, conditions were designed to test attention and access-to-toys hypotheses. Initial functional analyses suggested multiple control. Subsequent concurrent-schedule assessments identified preference between the reinforcers, and treatments were based on these findings. Findings are discussed regarding the assessment of potentially multiply controlled problem behavior.

Adult↗
PubMed1991

Structure-function analysis of the histidine permease and comparison with cystic fibrosis mutations.

Traffic ATPases constitute a superfamily of transporters that include prokaryotic permeases and medically important eukaryotic proteins, such as the multidrug resistance P-glycoprotein and the cystic fibrosis gene product. We present a structure-function analysis of a member of this superfamily, the prokaryotic histidine permease, using mutations generated both in vitro and in vivo, and assaying several biochemical functions. The analysis supports a previously predicted structural model and allows the assignment of specific functions to several predicted structural features. Mutations in the secondary structure features which form the nucleotide-binding pocket in general cause the loss of ATP binding activity. Mutations in the helical domain retain ATP binding activity. Several mutations have been identified which may affect the signaling mechanism between ATP hydrolysis and membrane translocation. We relate our findings to those emerging from the recent biochemical and genetic analyses of cystic fibrosis mutations.

ATP-Binding Cassette Transporters↗
PubMed1991

Transfer function analysis of the circulation: unique insights into cardiovascular regulation.

We have demonstrated previously that transfer function analysis can be used to precisely characterize the respiratory sinus arrhythmia (RSA) in normal humans. To further investigate the role of the autonomic nervous system in RSA and to understand the complex links between respiratory activity and arterial pressure, we determined the transfer functions between respiration, heart rate (HR), and phasic, systolic, diastolic, and pulse arterial pressures in 14 healthy subjects during 6-min periods in which the respiratory rate was controlled in a predetermined but erratic fashion. Pharmacological autonomic blockade with atropine, propranolol, and both, in combination with changes in posture, was used to characterize the sympathetic and vagal contributions to these relationships, as well as to dissect the direct mechanical links between respiration and arterial pressure from the effects of the RSA on arterial pressure. We found that 1) the pure sympathetic (standing + atropine) HR response is characterized by markedly reduced magnitude at frequencies greater than 0.1 Hz and a phase delay, whereas pure vagal (supine + propranolol) modulation of HR is characterized by higher magnitude at all frequencies and no phase delay; 2) both the mechanical links between respiration and arterial pressure and the RSA contribute significantly to the effects of respiration on arterial pressure; 3) the RSA contribution to arterial pressure fluctuations is significant for vagal but not for sympathetic modulation of HR; 4) the mechanical effects of respiration on arterial pressure are related to the negative rate of change of instantaneous lung volume; 5) the mechanical effects have a higher magnitude during systole than during diastole; and 6) the mechanical effects are larger in teh standing than the supine position. Most of these findings can be explained by a simple model of circulatory control based on previously published experimental transfer functions from our laboratory.

Adult↗
PubMed1991

A brief functional analysis of aggressive and alternative behavior in an outclinic setting.

We conducted a brief functional analysis to identify maintaining variable for aggressive behavior and an alternative replacement response during a 90-min outpatient evaluation of 3 individuals with severe handicaps. During the initial analogue assessment, which focused on identifying maintaining contingencies for aggressive behavior, each participant displayed a substantially greater frequency of aggressive behavior during one condition than during any other. The contingency that produced the highest percentage of aggressive behavior was then presented for the occurrence of a specific alternative behavior (a mand). During this contingency reversal phase, each participant displayed a substantial reduction in aggressive behavior and a substantial increase in alternative behavior, thus providing a direct analysis of the equivalency of the contingency for maintaining either behavior.

Adult↗
PubMed1992

Functional analysis of the expression of the 3'-phosphoglycerate kinase pgk gene in Aspergillus nidulans.

A functional analysis of the Aspergillus nidulans 3-phosphoglycerate kinase pgk promoter was undertaken using gene fusions to the lacZ gene of Escherichia coli, and introducing these into a beta-galactosidase-deficient strain of A. nidulans. Expression of a particular gene fusion in transformed strains depends upon the site of integration of the vector into the genome, and when specifically targeted to the catabolic quinate dehydrogenase qutE (selective marker) locus is directly proportional to its copy number. The analysis of transformed strains with single copies of pgk promoter deletion--lacZ fusions at the qutE locus identified three constitutive, positively acting sequence elements in the pgk gene. Sequence located between -161 and -120 nucleotides relative to the transcript start site +1, and including an element with a seven-out-of-eight nucleotide match (AAGCAAAT; -131 to -124) to the consensus eukaryotic octamer sequence ATGCAAAT, is essential for expression, and deletion of the complete 41-nucleotide sequence abolishes transcription. Sequence encompassing codons 14 to 183 and including the two introns of pgk contributes approximately one-third of the total activity, and far upstream sequence 5' to position -638 contributes approximately a further one-third total activity. In addition, sequence located -638 to -488 nucleotides, which includes an apparent consensus feature of A. nidulans glycolytic genes, affects carbon source-dependent regulation of expression. This region is required for an approximately 50% increase in pgk expression when A. nidulans is grown on gluconeogenic compared with glycolytic carbon sources.

Aspergillus nidulans↗
PubMed1985

Incremental value of the exercise treadmill test in determining the extent of coronary artery disease: a discriminant function analysis.

This study was undertaken to determine whether it was possible to use a multivariate discriminant function analysis to assess the severity of coronary artery disease in patients with angina pectoris. One hundred and forty-three patients diagnosed as having angina pectoris who formed a 'learning group' were subjected to an exercise test on a treadmill using a Bruce protocol. The items of data from the test least likely to be influenced by beta blockade were considered for the analysis along with two discrete variables (the gender and the use of beta blockers). All the patients subsequently underwent coronary angiography and the severity of the coronary artery disease was graded according to a scoring system. In addition, patients in 'learning group' were classified into two 'Groups', (I) those with normal vessels or with disease in one or two of the major arteries, (II) those with disease in the left main stem or in all three major arteries. The multivariate analysis yielded a score based upon 4 factors: (i) gender, (ii) percentage increase in double product at the highest level of exercise achieved, (iii) duration of ST depression in the recovery period and (iv) the summation of the ST depression in the standard electrocardiogram excluding lead aVR. There was a significant overall correlation between the discriminant function score and the coronary artery score for severity of the disease. In addition, it was found that, of patients having discriminant function score below 0, 96% (69/72) were in Group I. The post-test risk of a positive test was 0.005.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1998

Handedness identification from intertubercular sulcus of the humerus by discriminant function analysis.

The accurate determination of skeletal handedness is a critical requirement in physical anthropology and forensic science. To differentiate handedness, discriminant function analysis is applied using the parameters of right and left intertubercular sulci. A total of 200 matched unpaired adult humeri (100 right and 100 left), collected from the Department of Anatomy, were used to measure four parameters of the intertubercular sulcus namely, width (X1), depth (X2), angle of medial wall (X3) and angle of lateral wall (X4) and to note the presence of supratubercular ridge of Meyer (X5). The discriminant function obtained with the significant variables, angle of medial wall (X3), angle of lateral wall (X4) and presence of the supratubercular Meyer (X5) is: Y = 0.093X3 + 0.056X4 + 0.775X5 - 13.46. The accuracy of correct classification using the discriminant function is 89% which is the best starting point for handedness determination approach. The methodology of using discriminant function can be crucial for medicolegal jurisprudence.

Adult↗
PubMed1993

Functional analysis of the human neurofilament light chain gene promoter.

We have carried out a structural and functional analysis on the human NF-L (H-NF-L) gene. It contains a methylation-free island, spanning the 5' flanking sequences and the first exon and a number of neuronal-specific DNase I hypersensitive sites have been identified in the upstream region as well as within the body of the gene. Analysis in cell lines and transgenic mice using a combination of these sites has revealed the presence of a conserved element(s) between -300bp and -190bp which is required for neuronal-specific expression.

Animals↗
PubMed1989

The use of functional analysis of the ribosome as a tool to determine archaebacterial phylogeny.

Forty different antibiotics with diverse kingdom and functional specificities were used to measure the functional characteristics of the archaebacterial translation apparatus. The resulting inhibitory curves, which are characteristic of the cell-free system analyzed, were transformed into quantitative values that were used to cluster the different archaebacteria analyzed. This cluster resembles the phylogenetic tree generated by 16S rRNA sequence comparisons. These results strongly suggest that functional analysis of an appropriate evolutionary clock, such as the ribosome, is of intrinsic phylogenetic value. More importantly, they indicate that the study of the nexus between genotypic and phenotypic (functional) information may shed considerable light on the evolution of the protein synthetic machinery.

Archaea↗
PubMed1999

Functional analysis of the human D5 dopamine receptor missense and nonsense variants: differences in dopamine binding affinities.

The functional analysis of expressed human gene variants is important in the study of genetic susceptibility to diseases, pharmacogenetic traits and for the investigation of the human genetic diversity at the molecular level. We have performed the analysis of sequence polymorphisms in the human D5 dopamine receptor gene (DRD5) predicting missense and nonsense amino acid changes in the receptor protein. The amino acid substitutions in the human D5 dopamine receptor are: Leu88 to Phe in the putative second transmembrane domain, Ala269 to Val in the third intracellular and Pro330 to Gln in the third extracellular loops, Asn351 to Asp in the seventh transmembrane and Ser453 to Cys in the C-terminal domains and Cys335 to Stop in the third extracellular loop. The two amino acid substitutions in the transmembrane domains had an effect on agonist binding to the human D5 dopamine receptor. Asn351 to Asp resulted in an approximately 10-fold decrease in dopamine and threefold decrease in R(+)-SKF-38393 binding affinities. Leu88 to Phe resulted in a small increase in dopamine binding affinity. Antagonist binding affinities were mostly unaffected by the amino acid substitutions with the exception of Leu88 to Phe, which showed small reductions in binding affinities of SCH-23390 and risperidone. The existence of functionally different variants of the human dopamine receptors might have phenotypic consequences given their importance in central nervous system physiology and pharmacology.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1990

[Functional analysis of mutations on murine chromosome 17 using tertiary trisomy].

Analysis of the functional nature of mutations can be based on their manifestation in organisms with a deletion or a duplication of a particular chromosome segment. With the use of reciprocal translocation T(16;17)43H it is feasible to produce mice with tertiary trisomy for proximal region of chromosome 17. The mutations on chromosome 17 we tested included brachyury (T), hairpin tail (Thp), kinky (Fuki), quaking (qk), tufted (tf), as well as tct (t-complex tail interaction) and tcl (t complex lethal), that are specific for t haplotypes. The set of dominant and recessive mutations was assigned to two groups, one obligatory manifesting itself in the phenotype independently of the number of normal alleles in di- and trisomics, and the other facultative, phenotypically manifesting itself, depending upon the dosage of mutant alleles. A model was derived from analysis of the interaction of the T and Thp mutations with t haplotypes which is to explain the morphogenetic effects of the mutations observed in mice of different genotypes. The tir gene is postulated to reside on chromosome 17 within its framework. It is suggested that the gene dosage ratio at the tir and tct loci determines tail length.

Alleles↗
PubMed1991

Functional analysis of mutations of murine chromosome 17 with the use of tertiary trisomy.

Analysis of the functional nature of mutations can be based on comparisons of their manifestation in organisms with a deletion or duplication of a particular chromosome segment. With the use of reciprocal translocation T(16;17)43H, it is feasible to produce mice with tertiary trisomy of the proximal region of chromosome 17. The mutations on chromosome 17 we tested included brachyury (T), hairpin tail (Thp), kinky (Fuki), quaking (qk), tufted (tf), as well as tct (t complex tail interaction), and tcl (t complex lethal) that are specific to t haplotypes. The set of dominant and recessive mutations was assigned to two groups: one obligatory, manifesting itself in the phenotype independently of the number of normal alleles in di- and trisomics, and the other facultative, phenotypically manifesting itself depending upon the dosage of mutant alleles. A model was derived from analysis of the interaction of the T and Thp mutations with t haplotypes. It seeks to explain the morphogenetic effects of the mutations observed in mice of different genotypes. The tir gene is postulated to reside on chromosome 17 within its framework. It is suggested that the gene dosage ratio at the tir and tct loci determines tail length.

Alleles↗
PubMed1996

Functional analysis of grafts from living donors. Implications for the treatment of older recipients.

OBJECTIVE: Living-related liver transplantation (LRLT) has established efficacy in children. In a larger recipient, LRLT requires the use of a small graft because of limits on the donor hepatectomy. SUMMARY BACKGROUND DATA: The minimum graft weight required for successful transplantation has not been well established, although a characteristic pattern of graft dysfunction has been observed in our patients who receive small grafts. The authors present a clinicopathologic study of small liver grafts obtained from living donors. METHODS: Clinical and histologic data were reviewed for 25 patients receiving LRLT. In five older recipients (small group), the graft represented 50% or less of expected liver weight, whereas in 20 others (large group), the graft represented at least 60% of expected liver weight. A retrospective analysis of graft function was conducted by analyzing clinical parameters and histology. RESULTS: In the small group, 2 of 5 grafts (40%) were lost due to poor function, leading to one patient death (20% mortality), whereas in the large group, 2 of 20 grafts (10%) were lost due to arterial thrombosis without patient mortality. Early ischemic damage related to transplant was comparable with aspartate aminotransferase 203 +/- 23 (small group) and 290 +/- 120 (large group) at 24 hours (p = not significant). Early function was significantly decreased in the small group, with prothrombin time 18.2 +/- 2.2 seconds versus 14.8 +/- 1.6 seconds (large group) on day 3 (p = 0.034). All small group patients developed cholestasis with significantly increased total bilirubin levels at day 7 (16 +/- 5.2 mg% vs. 3.7 +/- 2.7 mg%; p = 0.021) and day 14 (12.0 +/- 7.4 vs. 1.8 +/- 0.7; p = 0.021) compared with the large group. Protocol biopsies in the small group revealed a diffuse ischemic pattern with cellular ballooning on day 7, which progressed to cholestasis in subsequent biopsies. Large group biopsies showed minimal ischemic changes. Three small group patients recovered with normal liver function by 12 weeks. CONCLUSIONS: Clinical recovery after a small-for-size transplant is characterized by significant functional impairment associated with paradoxical histologic changes typical of ischemia. These changes apparently are due to graft injury, which can only be the result of small graft size. These findings have significant implications for the extension of LRLT to adults.

Adolescent↗
PubMed1995

Functional analysis of linker insertions and point mutations in the alpha-Amy2/54 GA-regulated promoter.

Functional analysis of a gibberellin-regulated wheat alpha-amylase promoter, alpha-Amy2/54, has indicated that three regions were essential for expression. By studying the ability of mutant promoters, containing a randomly inserted 22 bp excision linker, to direct expression in oat aleurone protoplasts we have refined the positions and extents of these three cis elements and also demonstrated the presence of two additional elements. By converting the linker insertions to either single base point mutations or deletions using the class IIS restriction endonuclease BsmI we have shown that nucleotides -119 and -109 within the GARE -121GTAACAGAGTCTGG-108 and nucleotide -152 within the proposed element -156GATTGACTTGACC-144 are essential for high level expression from this promoter.

Base Sequence↗