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PubMedDate not supplied

Feasibility of ventricular function analysis by digital subtraction angiography.

Continuous or cine mode of digital subtraction angiography (DSA) following intravenous injection of contrast media was evaluated in regard to feasibility of obtaining physiologic data in cardiac abnormalities. Computer programs for cardiac function analysis including stroke volume, ejection fraction and display of left ventricular wall motion in end-diastole and end-systole have been developed with use of automatic contour plotting and densitometry for depth information. Experiments with contrast-filled balloons demonstrated good correlation between the true volumes and the calculated volumes. Clinical study also demonstrated good correlation between the values obtained from conventional left ventriculography and DSA.

Angiography↗
PubMed1992

Functional analysis of the rat insulin-like growth factor I gene and identification of an IGF-I gene promoter.

Insulin-like growth factor I (IGF-I) mediates many of the systemic growth-promoting effects of growth hormone and also functions as a locally acting growth stimulator. In mammals, IGF-I gene expression is complicated, as the gene is transcribed and processed into multiple mRNAs (ranging in length from less than 1 to nearly 7.5 kb) that encode at least two protein precursors. As a step toward understanding the regulation of IGF-I, we report the complete organization of the rat IGF-I gene, including identification of the structural determinants for all IGF-I mRNA species, and an initial functional analysis of its promoters. The gene is composed of 6 exons distributed over nearly 80 kb of chromosomal DNA and is structurally heterogeneous. Several transcription start sites were identified within IGF-I exons 1 and 2, adjacent to presumptive promoters 1 and 2, respectively, and at least three polyadenylation sites were mapped to exon 6. To test promoter function, fusion genes were constructed linking fragments of IGF-I DNA to a reporter plasmid. Chimeric genes containing at least 395 bp of DNA from the 5'-flanking region of exon 1 enhanced luciferase activity after transfection into the IGF-I-producing SK-N-MC cell line, while fusion plasmids containing up to 1,300 bp of DNA from the 5'-flanking region of exon 2 were inactive. Relative levels of IGF-I mRNAs containing exons 1 or 2 varied among different rat tissues, although in response to acute or chronic growth hormone treatment both classes of transcripts were induced coordinately in rat liver. These observations represent the first thorough characterization of a mammalian IGF-I gene, and provide a starting point for defining the mechanisms by which growth hormone and other trophic factors regulate IGF-I gene expression.

Amino Acid Sequence↗
PubMed1989

Disturbed endocrine function in the psychoses. II: Discriminant function analysis of multihormone data.

Discriminant function analyses were performed on plasma concentrations of prolactin, growth hormone, cortisol, TSH, and the neurophysins measured over 17 hours in 70 newly admitted drug-free psychiatric patients and 35 control subjects. The hormone data distinguished between patients with different classes of drug-free psychosis (26 schizophrenic, 12 with manic disorder, 10 with major depressive disorder, psychotic subtype, 9 with schizoaffective mania (SAM]. Higher plasma cortisol and lower TSH concentrations separated eight of nine SAM patients from all others.

Bipolar Disorder↗
PubMed1987

A functional analysis of recidivistic arson.

Evidence from studies of pathological arson and normal fire setting as well as the authors' clinical experience with arsonists in a maximum security hospital is employed to generate a model of recidivistic arson within the conceptual framework of functional analysis. It is contended that certain psychosocial stimuli, in the context of major setting conditions, predispose the individual towards incendiarism which is initially positively and negatively reinforced. However, the longer-term consequences of arson are considered to maintain and exacerbate the antecedent problems encountered by arsonists. Specifically, arson is viewed as an attempt to exert a change in the arsonist's life conditions where alternative behaviours have proved, or are perceived to be, ineffective. The model incorporates adaptations of the displaced aggression and arousal hypotheses of arson, and examines possible developmental aspects of pathological arson from normal childhood fire play, and suggests that a transition from fire setting in the company of others to incendiarism alone constitutes a major factor in the pathological process. The social, clinical and theoretical implications of the model are discussed with reference to current management and treatment strategies as well as future research.

Arousal↗
PubMed1978

[Intracellular regeneration and structuro-functional analysis of biological processes in normal cases and in pathology].

The author elucidates some problems in the history and the modern state in the doctrine on intracellular regenerative processes. Electron microscopic radioautography is considered as the most adequate method for studying intracellular regeneration. Certain examples are given to illustrate principally new possibilities of the structural-functional analysis of intracellular processes, normal and pathologic, studied by means of this method in view of the conception of intracellular generation. At the same time, new perspectives for further elaborating the problem of structural and functional integrity are stressed.

Animals↗
PubMed2026

Genome-wide association studies of plant traits and functional analysis of leaf development-related genes in citrus.

Labor-saving and high-light-efficiency tree architecture is a key breeding objective for woody fruit trees like citrus. However, population genetics information on these traits remains limited. In this study, tree architecture, thorn, and leaf traits were evaluated in 353 F2 progeny derived from a cross between Clementine mandarin and precocious trifoliate orange-an early-flowering variety. A random subset of 300 offspring was sequenced for a genome-wide association study (GWAS), which detected 10 216 significantly associated SNPs and defined several major quantitative trait loci (QTLs) for the target traits. Subsequent bulked segregant analysis (BSA) and GWAS on individuals with extreme compound leaf phenotypes mapped the causal gene(s) to a 0.8 Mb region (22.15-22.95 Mb) on chromosome 4. Genetic analysis across multiple hybrid combinations confirmed that the compound leaf trait in trifoliate orange is dominantly inherited and follows Mendelian segregation. Transcriptome profiling of parental leaves at different developmental stages identified a KNOX gene, CiKNAT6, as a candidate. Further validation using CAPS markers and Hi-Tom sequencing demonstrated tight linkage between an InDel polymorphism in CiKNAT6 and leaf shape across diverse citrus species and the F2 population, with co-segregation observed for the compound leaf trait. Due to alternative splicing producing seven splice variants, the CiKNAT6 DNA sequence was selected for genetic transformation experiments. Functional analysis revealed that the Clementine mandarin allele of CiKNAT6 is non-functional owing to an InDel, whereas ectopic expression of the trifoliate orange allele in tobacco and lemon induced leaf curling and reduced leaf size. CRISPR-Cas9 knockout of CiKNAT6 in trifoliate orange resulted in increased leaf area. These findings provide valuable genetic resources and insights for future studies on tree architecture and leaf morphology.

Plant Leaves↗
PubMed1988

Structure-function analysis of murine interferon-alpha: antiviral properties of novel hybrid interferons.

As described earlier the protein products of the murine interferon (IFN) genes MuIFN-alpha 1, -alpha 2, and -alpha 4 differ in their antiviral activity on hamster (CHO) and mouse (L929) cells. For structure-function analysis, hybrids were prepared between the three genes using common restriction enzyme sites. Natural and hybrid genes were transiently expressed in monkey COS cells. Under the conditions used IFN constituted 20-30% of the total amount of secreted proteins. Using a panel of hybrids either between alpha 1 and alpha 2 or between alpha 1, alpha 2, and alpha 4, the amino-terminal region of the protein, from amino acids 10 to 58, was found to determine its antiviral activity on hamster cells. On mouse cells, the antiviral activities of hybrids between alpha 4 and either alpha 1 or alpha 2 were compared. The high activity of alpha 4 (five to ten times that of alpha 1 or alpha 2) was not transmitted to hybrids having the amino-terminal part of alpha 4, but coincided with the presence of the alpha 4 carboxy-terminal region in all but one hybrid construct. The deletion of five amino acids (positions 103-107) located in this region of alpha 4 did not affect antiviral activity when introduced into MuIFN-alpha 2 and a MuIFN-alpha 42 hybrid by site-directed mutagenesis.

Animals↗
PubMed1985

Functional analysis of tight junction organization.

The functional basis of tight junction design has been examined from the point of view that this rate-limiting barrier to paracellular transport is a multicompartment system. Review of the osmotic sensitivity of these structures points to the need for this sort of analysis for meaningful correlation of structure and function under a range of conditions. A similar conclusion is drawn with respect to results from voltage-clamping protocols where reversal of spontaneous transmural potential difference elicits parallel changes in both structure and function in much the same way as does reversal of naturally occurring osmotic gradients. In each case, it becomes necessary to regard the junction as a functionally polarized structure to account for observations of its rectifying properties. Lastly, the details of experimentally-induced junction deformation are examined in light of current theories of its organization; arguments are presented in favor of the view that the primary components of intramembranous organization (as viewed with freeze-fracture techniques) are lipidic rather than proteinaceous.

Animals↗
PubMed1989

Transient expression of the angiotensin II receptor: a rapid and functional analysis of a calcium-mobilizing seven-transmembrane domain receptor in COS-7 cells.

The mas oncogene/angiotensin II receptor was subcloned into a mammalian expression vector pCDM8 and used to transiently transfect monkey kidney derived COS-7 cells. As a result, the mas transfected COS-7 cells expressed a functional angiotensin II receptor capable of transducing an increase in intracellular Ca2+ following stimulation with angiotensin II. The angiotensin II stimulated changes in Ca2+ could be measured 24 hours after transfection in both a fluorimeter and a fluorescence activated cell sorter. These results describe a rapid method for the functional analysis of the 7-transmembrane domain receptor genes.

Angiotensin II↗
PubMed1991

Controlling extremely dangerous aggressive outbursts when functional analysis fails.

This article describes and illustrates a treatment program aimed at addressing intermittent extremely dangerous aggressive behavior in an 11-year-old girl who was blind, multiply handicapped, and profoundly mentally retarded. In the month preceding treatment she had injured a peer, a paid careprovider, and her mother. Functional analysis produced no clear antecedents to aggression. Punishment was used to introduce a superordinate contingency. Differential reinforcement of alternative behavior combined with contingent restraint reduced, then eliminated aggression. Follow-up at an age equivalent of 4 years, 6 months indicated a continued absence of aggression. Results are discussed in regards to the balance between research methodology, agency policy, right to effective treatment, and social validity.

Aggression↗
PubMed1985

Functional analysis of fractionated Drosophila Kc cell tRNA gene transcription components.

We have previously described the partial purification of RNA polymerase III transcription components from Drosophila Kc cell extracts (Burke, D. J., Schaack, J., Sharp, S., and Söll, D. (1983) J. Biol. Chem. 258, 15224-15231). Here we report further physical and functional analysis of the two transcription-required fractions designated as factors B and C. Using stable complex formation-competition experiments with ordered addition of these transcription components, we have shown that factor C associates rapidly with the tRNA gene, but will not form a stable complex with the DNA in the absence of factor B. Reconstitution experiments of the individual Drosophila Kc cell factors with those from human HeLa cells demonstrated that the HeLa factor B, combined with Kc factor C, can form active transcription complexes. These now exhibit a property of the Drosophila system, a strong dependence on sequences in the 5'-flanking regions of tRNA genes. However, the Kc factor B (which has an apparent molecular weight of 260,000 as judged by gel filtration analysis) is not compatible with the HeLa factor C. These results, together with the isolation of a large complex containing all necessary transcription components, emphasize the importance of the interaction of these components for both stable complex formation and transcription initiation.

Animals↗
PubMed1983

Clonal expansion and functional analysis of virus-specific T lymphocytes from cerebrospinal fluid in measles encephalitis.

T cells were directly cloned from the cerebrospinal fluid (CSF) of a patient with acute measles encephalitis by limiting dilution in the presence of irradiated feeder cells and T cell growth factor (TCGF). A total of 42 colonies was established. Functional analysis revealed 27 of them to be derived from a cytotoxic T lymphocyte as demonstrated by the ability to exert phytohaemagglutinin (PHA)-dependent cytotoxicity against uninfected allogeneic PHA blasts. Twenty-three of the cytotoxic colonies were specific for measles virus and restricted to self HLA-A or -B antigens. Three clones were also found to give measles virus-specific proliferative responses. The results show that the CSF in measles encephalitis contains a highly enriched population of in vivo sensitized antigen-specific T cells. We propose that the clinical symptoms in measles encephalitis are caused by a T cell-mediated reaction against virus-infected brain cells.

Child↗
PubMed1992

Cloning, organization and functional analysis of ilvA, ilvB and ilvC genes from Corynebacterium glutamicum.

Corynebacterium glutamicum is an industrially important bacterium for the manufacture of amino acids. We constructed genomic libraries of this Gram+ bacterium and screened for clones carrying isoleucine biosynthesis genes (ilv) by complementation of Escherichia coli mutants. Clones complementing ilvA, ilvB, and ilvC were isolated. As based on the functional analysis of the corresponding plasmids in C. glutamicum, the DNA fragments isolated encode threonine dehydratase, acetohydroxy acid synthase, and isomeroreductase, catalyzing three subsequent reactions in Ile synthesis. Subcloning and transposon mutagenesis revealed that ilvB and ilvC reside on a 7-kb chromosomal fragment and that these genes are transcribed in the same direction. A shuttle vector was constructed to allow exonuclease treatment and assay subsets of plasmids for gene expression in the original C. glutamicum background. These constructs and their enzyme activity determinations revealed that despite close linkage ilvC is expressed independently from ilvB. Using Southern blots, a 15-kb fragment of chromosomal DNA carrying the ilvBC cluster was characterized. This fragment does not contain ilvA, demonstrating the entirely different organization of the isoleucine biosynthesis genes in C. glutamicum from that in enterobacteria.

Acetolactate Synthase↗
PubMed1978

Toward a biochemical classification of depressive disorders. II. Application of multivariate discriminant function analysis to data on urinary catecholamines and metabolites.

The previous article in this series reported on the differences in urinary excretion of 3-methoxy-4-hydroxyphenylglycol (MHPG) in patients with various clinically defined subtypes of depressive disorders. We now report that further biochemical discrimination among depressive subtypes is provided by the following equation, derived empirically by applying multivariate discriminant function analysis to data on urinary catecholamine metabolits: Depression-type (D-type) score = C1(MHPG) + C2(VMA) + C3(NE) +C4(NMN + MN)/VMA + C0. In the original derivation of this equation, low scores were related to bipolar manic-depressive depressions, and high scores were related to unipolar nonendogenous (chronic characterological) depressions. Findings from a series of depressed patients whose biochemical data had not been used to derive this equation confirmed these differences in D-type scores among subtypes of depressions. The findings presented in this report further suggest that we can discriminate three biochemically discrete subgroups of depressive disorders.

Adult↗
PubMed1990

Structure-function analysis of human IL-6. Epitope mapping of neutralizing monoclonal antibodies with amino- and carboxyl-terminal deletion mutants.

To study the active site(s) of IL-6 we combined mutagenesis of IL-6 with epitope mapping of IL-6 specific mAb. In addition to amino-terminal deletion mutants we described previously, carboxyl-terminal deletion mutants were prepared. Functional analysis showed that deletion of only five carboxyl-terminal amino acids already reduced the bioactivity 1000-fold. A panel of mAb to IL-6 was subsequently analyzed by antibody competition experiments and binding to the amino- and carboxyl-terminal deletion mutants. On the basis of the competition experiments the six neutralizing mAb were divided in two groups (I and II). The binding pattern with the deletion mutants suggested that the region recognized by the four mAb in group I is composed of residues of amino- and carboxyl-terminus: binding of two mAb was abolished after deletion of amino acid Ala I-Ile26, of the third mAb after deletion of the four carboxyl-terminal amino acids whereas the fourth mAb did not bind to either mutant. Group II mAb retained binding to these mutants. Taken together these data suggest that in the native IL-6 molecule amino acid residues of amino and carboxyl terminus are in close proximity and that together they constitute an active site. Furthermore our data suggest that the part of the molecule recognized by group II antibodies is a second site involved in biologic activity.

Amino Acid Sequence↗
PubMed1992

Structure-function analysis of hepatocyte growth factor: identification of variants that lack mitogenic activity yet retain high affinity receptor binding.

Hepatocyte growth factor (HGF) is a potent mitogen for parenchymal liver, epithelial and endothelial cells. Structurally, it has similarities to kringle-containing serine proteases, although it does not possess proteolytic activity. A structure-activity relationship study of human HGF was performed by functional analysis of HGF substitution and deletion variants. Analysis of HGF variants was accomplished by defining their ability to induce DNA synthesis on hepatocytes in primary culture and to compete with wild-type HGF for binding to a soluble form of the HGF receptor. Three groups of variants were made: (i) substitutions at the cleavage site, (ii) substitutions within the protease-like domain and (iii) deletions of the beta-chain and/or kringle domains. Our results show that: (i) single-chain HGF is a zymogen-like promitogen in that cleavage into a two-chain form is required for biological activity, however, the single chain form of HGF still retains substantial receptor binding capacity; (ii) certain mutations in the protease-like domain result in variants that are completely defective for mitogenic activity, yet exhibit apparent receptor binding affinities similar to wild-type HGF (Kd approximately 50-70 pM); and (iii) a variant containing the N-terminal 272 residues of mature HGF showed only a 4-fold increase in Kd when compared with wild-type HGF indicating that a primary receptor binding determinant is located within this sequence.

Animals↗