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At least 127 records · Page 7Linked to original sources

PubMed1991

Functional hepatic imaging with receptor-binding radiopharmaceutical: clinical potential as a measure of functioning hepatocyte mass.

Asialoglycoprotein receptor (ASGP-R) is a hepatic cell surface receptor specific for galactose-terminated glycoproteins. Technetium-99m diethylenetriaminepentaacetic acid-galactosyl human serum albumin (TcGSA) is a newly developed analog ligand to ASGP-R. Fourteen human subjects were studied: three normal volunteers, one with chronic hepatitis, 6 with liver cirrhosis, and 4 with hepatocellular carcinoma associated with liver cirrhosis. The receptor index parameter (LHL15), was obtained from the liver and heart time-activity data as the ratio of radioactivity of the liver over that of the liver plus heart at 15 min after intravenous injection of 1 mg of TcGSA. Means +/- standard deviations of LHL15 in normal volunteers (3 cases), patients with mild (4 cases), moderate (2 cases), and severe liver damage (5 cases) were 0.933 +/- 0.006, 0.789 +/- 0.045, 0.723 +/- 0.033, and 0.488 +/- 0.094, respectively. The difference between the mean values of each group was statistically significant (P less than 0.05). LHL15 correlated well with classical indicators for hepatic functional capacity such as serum albumin level, serum bilirubin level, prothrombin time, ICG R15 or Child-Turcotte criteria score. Our preliminary experiences of high correlations of TcGSA functional imaging data with clinical data suggest that the dynamic data using this receptor-binding radiopharmaceutical provides invaluable information with regard to liver function, and thus, the TcGSA study is potentially a noninvasive practical tool to measure functioning hepatocyte mass.

Asialoglycoprotein Receptor↗

PubMed1986

A comparative study on the effects of inhibitors of the lipoxygenase pathway on neutrophil function. Inhibitory effects on neutrophil function may not be attributed to inhibition of the lipoxygenase pathway.

The effects of five inhibitors of the lipoxygenase pathway were evaluated on oxygen radical production, degranulation, chemotaxis, leukotriene B4 (LTB4) production by neutrophils. The lipoxygenase inhibitors tested were nordihydroguaiaretic acid (NDGA), esculetin, eicosatetraynoic acid (ETYA), 2-(12-hydroxydodeca-5,10-diynyl)-3,5,6-trimethyl-1,4-benzoqu inone (AA-861), and 6,9-deepoxy-6, 9-(phenylimino)-delta 6.8-prostaglandin I1 (U-60,257). Neutrophils were activated by n-formyl-methionyl-leucyl-phenylalanine (fMLP), phorbol myristate acetate (PMA), A23187, or platelet activating factor (PAF). The effects of these inhibitors on NADPH oxidase activity and phospholipase A2 activity of isolated particulate fraction of neutrophils were also evaluated. ETYA inhibited neutrophil function induced by all the stimulators except PMA. AA-681 was unique in that it did not inhibit PAF-induced neutrophil activation. U-60,257 had virtually no effect on oxygen radical production and degranulation, but chemotaxis was moderately suppressed. NDGA effectively inhibited neutrophil function, except for chemotaxis. Esculetin inhibited only oxygen radical production, but this was due to inhibition on NADPH oxidase activity of neutrophil membrane. The inhibitory effect on neutrophil function and that of LTB4 production were not closely correlated. It is suggested that lipoxygenase inhibitors may modify neutrophil function by the mechanism not involving the lipoxygenase pathway. It is also suggested that LTB4 may not be a mediator in neutrophil oxygen radical production and degranulation induced by the stimulators used in the present study.

5,8,11,14-Eicosatetraynoic Acid↗

PubMed1990

Functional substitution of the basic domain of the HIV-1 trans-activator, Tat, with the basic domain of the functionally heterologous Rev.

The tat gene of HIV is a strong activator of the viral LTR. The Tat protein contains a highly basic domain that is important for its transport to the nuclear/nucleolar locations. The Tat basic domain when fused to Escherichia coli beta-galactosidase directed the chimeric protein to the nucleus and nucleolus. Tat mutants lacking the entire basic domain were severely defective in trans-activation. Substitution of the basic domain of Tat with that of the functionally unrelated HIV-1 Rev protein targeted the chimeric protein to the nucleolus and restored the function of Tat. In contrast, substitution with the nuclear targeting signal (NLS) of SV40 T antigen targeted the chimeric protein to the nucleus and accumulation in the nucleolar region was excluded. The Tat-NLS chimeric protein did not restore the trans-activation function of Tat efficiently. These results indicate that the arginine-rich basic domain of the trans-activator, Tat, and post-transcriptional trans-regulator, Rev, are functionally similar with regard to trans-activation of HIV-1 LTR.

Amino Acid Sequence↗

PubMed1991

Phenotypic and functional characteristics of activated CD8+ cells: a CD11b-CD28- subset mediates noncytolytic functional suppression.

Freshly isolated human CD8+ cells can be divided into mutually exclusive subsets bearing the phenotypes CD11b+(CD28-) or CD28+(CD11b-). We found that activation of CD8+ cells with anti-CD3 mAb and IL-2 preferentially expanded the CD11b-(CD28+) subset. This subset, when separated and activated independently, mediated both functional suppression and lectin-dependent cell cytotoxicity (LDCC). CD28- cells, prepared by elimination of the CD 28+ cells from expanded unfractionated CD8+ cell cultures, retained functional suppressor activity but demonstrated reduced LDCC compared to either the CD28+(CD11b-)-enriched fraction or the unfractionated CD8+ population. The majority of the CD28- cells were also CD11b-, reflecting the observation that initially CD11b+ cells lose CD11b expression following activation with anti-CD3 mAb and IL-2. Our results therefore indicate that CD8+ cells deriving from the CD11b+CD28- subset, but expressing neither CD11b nor CD28 after activation, represent the main noncytotoxic functional suppressor cell in the mitogen "activated" suppressor assay. The preferential expansion of CD8+CD28+ cells relative to CD8+CD28- cells, if occurring in vivo in the central nervous system (CNS) compartment, would be consistent with observed phenotypic analysis of cerebrospinal fluid-derived T cells and might contribute to the reduced functional suppressor activity previously found for CNS compared to peripheral blood-derived lymphocytes.

Antibodies, Monoclonal↗

PubMed2026

Divergent PXR function in seals: Endocrine adaptation or functional loss?

Seals accumulate xenobiotics through dietary biomagnification and exposure to polluted marine environments, with contaminants concentrating in their blubber. Biotransformation mitigates xenobiotic toxicity by converting lipophilic compounds into excretable hydrophilic metabolites, a process coordinated by nuclear receptors including the Pregnane X Receptor (PXR), whose plastic ligand-binding domain enables broad xenobiotic sensing. By examining PXR in pinnipeds, we investigated the evolutionary conservation and functional characterization of PXR using genomic sequence analysis, protein structural prediction, and transactivation assays, revealing broadly conserved structural features alongside species-specific functional divergence in receptor responsiveness to environmental stressors. Specifically, the obtained results highlight divergent gene and functional landscapes with ORF-disrupting mutations identified in Monachus monachus and Neomonachus schauinslandi that abolish receptor activation toward known PXR ligands. In contrast, Leptonychotes weddelli retained an intact PXR ORF but showed reduced receptor activity, revealing functional divergence in PXR among pinnipeds.

Biotransformation↗

PubMed1988

A transcription-translation activation feedback circuit as a function of protein degradation, with the quality of protein mass adaptation related to the average functional load.

The balance between protein synthesis and degradation, and between active skeletal muscle cell hypertrophy and atrophy can be described as a function of protein degradation rate by a transcription-translation activation control loop. Transcription activity is presumed to be determined by the concentration of protein-specific fragments (PSF) occurring as intermediate products of protein degradation. If PSF acts as an apoinducer at the gene or operon enhancer region, formation and dissociation of PSF-enhancer complex, as a function of PSF concentration, determines the gene or operon transcription activity. The assumed regulation can be converted to a mathematical model that allows simulation of steady-state protein balance and active adaptation, according to the level of functional activity. The relationship between steady-state transcription activity and PSF concentration can be described by Michaelis-Menten or weak sigmoidicity kinetics. Similar dependency is presumed in translation activity as a function of mRNA concentration. The relationship of protein to mRNA, PSF and ribosome content, and their formation and degradation, are determined by first-order differential equations. The assumed regulation scheme may also contribute to the theory of transcription activation, and can be used to explain the mechanism determining active adaptation in living systems.

Feedback↗

PubMed1987

Condylar position following ramus osteotomy and functional osteosynthesis. A clinical function-analytic and computer tomographic study.

Opponents of the application of a stable fixation of the fragments with compression screws in osteotomies of the mandibular ramus quite often claim that there is the possibility of a postoperative dislocation of the proximal fragment with consequent functional disturbances of the temporo-mandibular joint. For determination of the frequency and the extent of such possible displacements of the condyle, a total of 174 patients, in whom ramus osteotomies were performed, were clinically examined. In 9 of them, a functional analysis and in 10 other patients, a CT scan investigation of the position of the TM joint, was carried out. Only in 1 case could a considerable dislocation of the proximal fragment be observed, which was due to a strong unilateral deviation of the ascending ramus. For correction of the functional disturbance the bone screws had to be removed in this particular case. In those cases where a functional analysis and CT study were undertaken, only slight changes of the pre- and post-operative position of the condyles were observed: it did not lead to clinical disturbances and complaints.

Bone Screws↗

PubMed1987

Family functioning and functional independence in spinal cord injury adjustment.

The relationships among functional independence, perceived family functioning and duration of disability were studied in 41 non-institutionalised post-traumatic spinal cord injury (SCI) families. Correlational analyses revealed that SCI subjects with greater self initiation of activities, increased social involvement and higher overall level of independence perceived their family environment as affectively responsive, open in communication and clear in delineation of role responsibilities. The 'significant other's' (A 'significant other' is designated by the SCI subject as 'the one most involved with you'. The 'significant other' had to be living with or within 25 miles of the SCI subject and in contact at least 3 times a week.) view of the family was unrelated to SCI function. Conversely, for the significant other but not the SCI subject, greater duration of disability predicted more concern for the family's ability to problem solve, delineate roles and maintain standards of behaviour control. Of the functional areas measured, only participation in outside activities increased significantly over time. The results are discussed in terms of the importance of considering the long-term and separate rehabilitation needs of the individual with a SCI and his or her family.

Activities of Daily Living↗

PubMed1971

Similar idiotypic specificities in immunoglobulin fractions with different antibody functions or even without detectable antibody function.

IDIOTYPY HAS BEEN STUDIED IN ANTIBODIES AGAINST A PROTEIN ANTIGEN: hen ovalbumin. Various fractions of antisera to hen ovalbumin have been compared from the standpoint of the idiotypic specificities found on the immunoglobulins that they contain. Idiotypic specificities were found to be common to (a) antibodies that were not eluted from the same immunoadsorbent by the same MgCl(2) concentration, but by four different concentrations. (b) Antibodies that were precipitable only by hen ovalbumin, only by hen and turkey ovalbumin, or also by duck ovalbumin. (c) Antibodies that were precipitated or not precipitated by the homologous ovalbumin, and proteins apparently devoid of antiovalbumin antibody function. These findings are discussed from the standpoint of (i) the differences in function between the various fractions with the same idiotypic specificities, and (ii) what may be common in the cellular origin of immunoglobulins with a common idiotypic specificity, and what may be different in immunoglobulins with different antibody functions or without antibody function. The same idiotypic specificities have been found in certain IgG and IgM antiovalbumin antibodies.

Animals↗

PubMed1990

Functions of replication factor C and proliferating-cell nuclear antigen: functional similarity of DNA polymerase accessory proteins from human cells and bacteriophage T4.

The proliferating-cell nuclear antigen (PCNA) and the replication factors A and C (RF-A and RF-C) are cellular proteins essential for complete elongation of DNA during synthesis from the simian virus 40 origin of DNA replication in vitro. All three cooperate to stimulate processive DNA synthesis by DNA polymerase delta on a primed single-stranded M13 template DNA and as such can be categorized as DNA polymerase accessory proteins. Biochemical analyses with highly purified RF-C and PCNA have demonstrated functions that are completely analogous to the functions of bacteriophage T4 DNA polymerase accessory proteins. A primer-template-specific DNA binding activity and a DNA-dependent ATPase activity copurified with the multisubunit protein RF-C and are similar to the functions of the phage T4 gene 44/62 protein complex. Furthermore, PCNA stimulated the RF-C ATPase activity and is, therefore, analogous to the phage T4 gene 45 protein, which stimulates the ATPase function of the gene 44/62 protein complex. Indeed, some primary sequence similarities between human PCNA and the phage T4 gene 45 protein could be detected. These results demonstrate a striking conservation of the DNA replication apparatus in human cells and bacteriophage T4.

Adenosine Triphosphatases↗

PubMed1992

Functional analysis of the transcriptional activator encoded by the maize B gene: evidence for a direct functional interaction between two classes of regulatory proteins.

The B, R, C1, and Pl genes regulating the maize anthocyanin pigment biosynthetic pathway encode tissue-specific transcriptional activators. B and R are functionally duplicate genes that encode proteins with the basic-helix-loop-helix (b-HLH) motif found in Myc proteins. C1 and Pl encode functionally duplicate proteins with homology to the DNA-binding domain of Myb proteins. A member of the b-HLH family (B or R) and a member of the myb family (C1 or Pl) are both required for anthocyanin pigmentation. Transient assays in maize and yeast were used to analyze the functional domains of the B protein and its interaction with C1. The results of these studies demonstrate that the b-HLH domain of B and most of its carboxyl terminus can be deleted with only a partial loss of B-protein function. In contrast, relatively small deletions within the B amino-terminal-coding sequence resulted in no trans-activation. Analysis of fusion constructs encoding the DNA-binding domain of yeast GAL4 and portions of B failed to reveal a transcriptional activation domain in the B protein. However, an amino-terminal domain of B was found to recruit a transcriptional activation domain by an interaction with C1. Formation of this complex resulted in the activation of a synthetic promoter containing GAL4 recognition sites, demonstrating that this interaction does not require the normal target promoters for B and C1. B and C1 fusions with yeast GAL4 DNA-binding and transcriptional activation domains were also found to interact when synthesized and assayed in yeast. The domains responsible for this interaction map to a region that contains the Myb homologous repeats of the C1 protein and to the amino terminus of the B protein, which does not contain the b-HLH motif. These studies suggest that the regulation of the maize anthocyanin pigmentation pathway involves a direct interaction between members of two distinct classes of transcriptional activators.

Anthocyanins↗

PubMed1990

Functional analysis of mononuclear cells infiltrating into tumors: establishment of a new system to obtain functionally active tumor-infiltrating cells.

We have demonstrated that tumor-infiltrating T cells play a crucial role in tumor growth. In order to investigate the precise function of tumor-infiltrating cells, we avoided the use of any enzyme for separation of tumor-infiltrating cells from the solid tumor mass and established a new system in which we could easily obtain functionally active tumor-infiltrating cells in large amounts from the peritoneal cavity of T-9 gliosarcoma-sensitized rats. In this system, viable T-9 cells were intraperitoneally administered and peritoneal exudate cells were recovered. Importantly, cells obtained from the intraperitoneal cavity are phenotypically and functionally indistinguishable from those obtained from subcutaneous tumor masses. Furthermore, injection of purified lymphocyte migration factor-b resulted in the accumulation of CD8 (+) cytotoxic T cells in the peritoneal cavity. Therefore, this system also provides a means by which the in vivo function of chemotactic factor can be tested.

Animals↗

PubMed1992

High-dose inhaled steroids in the management of asthma. A comparison of the effects of budesonide and beclomethasone dipropionate on pulmonary function, symptoms, bronchial responsiveness and the adrenal function.

The efficacy of budesonide (800 micrograms b.d.) and beclomethasone dipropionate (750 micrograms b.d.) in controlling the symptoms of asthma, pulmonary function, bronchial responsiveness to histamine, and adrenal function, was assessed in a double-blind, double-dummy cross-over study of 36 adult chronic asthmatic patients. The patients, the majority of whom were assessed to be affected to a severe degree, were insufficiently controlled in their current regimen of inhaled steroids and/or inhaled and oral bronchodilators. A 2 weeks baseline period preceded 6 weeks of treatment with each of the study drugs. Both treatment groups showed improvements from baseline in clinical assessment of lung function carried out after the first 6 weeks of treatment. No significant differences were seen throughout the entire 12 weeks study, when comparing the effects of the treatments on FEV1, FVC, PEF or the histamine PC20. Asthma severity, symptom score and inhaled bronchodilator use showed the same results after both treatments. It is concluded that inhalations of budesonide and beclomethasone dipropionate in high doses are equally potent in the treatment of severe asthma. There is no significant influence on the adrenal function and no significant side effects during a period equal to that of the present study.

Administration, Inhalation↗

PubMed1991

Executive function deficits in high-functioning autistic individuals: relationship to theory of mind.

A group of high-functioning autistic individuals was compared to a clinical control group matched on VIQ, age, sex and SES. Significant group differences were found on executive function, theory of mind, emotion perception and verbal memory tests, but not on spatial or other control measures. Second-order theory of mind and executive function deficits were widespread among the autistic group, while first-order theory of mind deficits were found in only a subset of the sample. The relationship of executive function and theory of mind deficits to each other, and their primacy to autism, are discussed.

Adolescent↗

PubMed1985

Effects of L-canavanine on immune function in normal and autoimmune mice: disordered B-cell function by a dietary amino acid in the immunoregulation of autoimmune disease.

This study reports the effects in vitro and in vivo of L-canavanine (LCN), an amino acid found in commonly consumed legumes, on immune function in normal and autoimmune mice. L-Canavanine in high doses effectively blocks all DNA synthesis in vitro within 24 h. At lower doses, LCN affects B-cell function of autoimmune New Zealand Black/New Zealand White (NZB/NZW)F1 mice, inhibiting [3H]thymidine incorporation in response to B-cell mitogens, and pokeweed-induced intracytoplasmic immunoglobulin synthesis. LCN stimulates intracytoplasmic immunoglobulin (IgG greater than IgM). T-cell functions such as lymphoproliferation in response to concanavalin A or phytohemagglutinin and T-cell cytotoxicity are not affected. Suppression of the lipopolysaccharide response by LCN is removed by the addition of fresh B cells. Addition of the amino acid to mouse diet resulted in a decrease in the life-span of the autoimmune NZB and (NZB X NZW)F1 mice and abolished the protective effect of male sex on their survival. The decrease in survival in LCN-treated autoimmune mice correlated with an increase in spontaneous immunoglobulin-secreting cells (IgG greater than IgM) and antinuclear and double-stranded DNA antibodies. The histopathological analyses revealed increased glomerular damage and immunoglobulin deposition in the kidneys of the LCN-treated autoimmune and normal (DBA/2) mice. Ten percent of normal mice developed high titers of autoantibodies after 24 weeks of the diet. These data suggest a dietary amino acid, L-canavanine, affects B-cell function resulting in autoimmune phenomena and providing a new animal model of autoimmunity, a diet-induced systemic lupus erythematosus.

Animals↗

PubMed1991

The effect of high buffer cardioplegia and secondary cardioplegia on cardiac preservation and postischemic functional recovery: a 31P NMR and functional study in Langendorff perfused pig hearts.

High buffer cardioplegia may provide protection against ischemic damage by reducing the extent of intracellular acidosis. Secondary cardioplegia may improve postischemic recovery by restoration of high energy phosphates, ionic gradients, and intracellular pH. To test these hypotheses, pig hearts were arrested with high buffer (150 mM MOPS) cardioplegia or modified St. Thomas' solution II and then kept ischemic at 12 degrees C for 8 h. High energy phosphates and intracellular pH were followed during the period of ischemia, using 31P nuclear magnetic resonance spectroscopy, and functional recovery was followed during reperfusion. The hearts arrested by high buffer cardioplegia showed significantly higher intracellular pH than hearts preserved with St. Thomas' solution, but there were no significant differences in high energy phosphates. There were no significant differences in functional recovery. We found, however, that secondary cardioplegia abolished ventricular fibrillation, and resulted in improved functional recovery after 8 h of ischemic preservation compared with the hearts reperfused with Krebs-Henseleit solution alone. Our results suggest that despite attenuating the decreases in intracellular pH, high buffer cardioplegia does not improve recovery following 8 h of preservation at 12 degrees C. Secondary cardioplegia reduces the incidence of ventricular fibrillation and improves postischemic functional recovery of the myocardium.

Adenosine Triphosphate↗

PubMed1984

The relationship between cognitive function and liver function in alcoholism.

Thirty alcoholic patients were investigated for evidence of impaired hepatic function and deficits in cognitive functioning, to see if there was any significant relationship between these two complications of alcoholism. Forty-seven per cent had abnormal gamma-glutamyl transpeptidase levels, and 63 per cent had abnormal results on the Category test. Only one significant correlation coefficient was found, between one parameter of hepatic function and one of cognitive function. Possible explanations for this (negative) correlation are discussed, and the value of further study is suggested.

Adult↗

PubMed1988

Phase-transfer function of the human eye and its influence on point-spread function and wave aberration.

The bidimensional phase-transfer function (PTF) of the human eye has been computed from aerial retinal images of a point test. These images were previously determined by using a recently developed hybrid optical-digital method. Actual PTF data have been obtained directly without linear variations with spatial frequency and have shown great variations among individual subjects. The influence of the PTF on the determination of the point-spread function and the wave-aberration function for emmetropized and slightly astigmatic subjects has been also evaluated. Finally, the effect of pupil size on the PTF was determined by computing these functions from the wave aberration. These results allow us to give a more thorough description of the optical image quality of the human eye and can be used as actual data in subsequent psychophysical studies.

Humans↗