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At least 19 recordsLinked to original sources
PubMed2026

Early-stage trajectories of social-occupational functioning and long-term functional outcome prediction in early psychosis: A 12-year follow-up of the randomized controlled trial on extended early intervention.

BACKGROUND: Functional impairment in psychosis often persists despite symptomatic remission. There is a paucity of research examining early-course psychosocial functioning trajectories, and none has been conducted to examine relationship between the trajectories and prospective long-term functional outcomes in early psychosis sample. METHODS: We conducted 12-year follow-up of a randomized controlled trial on extended early intervention for first-episode psychosis to identify early-course social-occupational functioning trajectories and their baseline predictors and associations with 12-year outcomes. Participants who completed Social and Occupational Functioning Scale (SOFAS) scores at three or more timepoints between baseline and 3-year follow-up were included in the study. Premorbid adjustment, illness characteristics, symptom severity, functioning, and treatment profiles were assessed. Latent growth mixture modeling was employed to derive early-course social-occupational functioning trajectories based on SOFAS scores over 3-year follow-up. RESULTS: A total of 148 participants were included in this study, with 106 patients having completed the 12-year follow-up. Our results identified four distinct trajectories, including persistently-good class, gradually-improved class, suboptimal-stable class, and persistently-poor class. Patients in persistently-poor class had more severe negative symptoms at baseline compared to patients in persistently-good class. Patients with persistently-poor trajectory had worse long-term outcomes than those with other classes in the majority of functional measures at 12-year follow-up. CONCLUSIONS: The majority of patients were classified in early-stage suboptimal or poor functional trajectories. Above one-fourth of the participants exhibited persistently-poor social-occupational functioning trajectory, which predicted worse functional outcomes at 12-year follow-up. These findings highlighted the importance of tracking functional changes during the initial years of illness.

Humans↗
PubMed1975

Effects of colchicine and cycloheximide on the functional and non-functional lipoprotein lipase fractions of rat heart.

In response to food deprivation, total myocardial lipoprotein lipase activity increased gradually over a period of 9 h. Although lipoprotein lipase exists in a functional and non-functional form in the myocardium, most of the increas in activity occurred in the functional (heparin-releasable) lipoprotein lipase fraction. The administration of colchicine, while having no effect on the increase seen in total lipoprotein lipase activity, did inhibit the increase in the functional fraction, while at the same time, caused a marked rise in the activity of the non-functional (non-releasable) fraction. In rats injected with colchicine after a 24-h fast, total lipoprotein lipase activity was not affected, but activity levels in the functional fraction declined while that in the non-functional fraction increased. These results suggest that the functional lipoprotein lipase is constantly being formed in sites not readily accessible to heparin (presumably the myocardial cells) and transported to its site of action, the surface of the endothelial cells of the capillaries. Cycloheximide administration to rats starved for 24 h caused a decline in activity in both the functional (half-life of about 2 h) and the non-functional (half-life of about 4 h) lipoprotein lipase fractions. These results suggest that the functional and non-functional lipoprotein lipase fractions may correspond to two distinct enzyme species.

Animals↗
PubMed1992

Catecholamine synthesizing enzymes in 70 cases of functioning and non-functioning phaeochromocytoma and extra-adrenal paraganglioma.

Immunohistochemical localization of the catecholamine synthesizing enzymes, tyrosine hydroxylase (TH), aromatic L-amino acid decarboxylase (AADC), dopamine-beta-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT), was investigated in 70 cases of functioning and non-functioning phaeochromocytomas comprising 52 of adrenal and 18 of extra-adrenal origin. Of 59 functioning tumours, 30 were mixed epinephrine and norepinephrine-producing (mixed type) and 29 were norepinephrine-producing tumours. TH, AADC and DBH were detected in all functioning phaeochromocytomas, but PNMT was limited to the mixed-type phaeochromocytomas. Non-functioning phaeochromocytomas were divided into two groups, comprising a complete type, which induced neither elevated plasma catecholamines nor their metabolites in urine, and an incomplete type which exhibited no elevated plasma catecholamines, but showed a slightly high urinary vanillylmandelic acid level. In the non-functioning complete-type tumours, immunoreactive TH was negative, but the incomplete tumours of the adrenal medulla had all four enzymes, and corresponded to a mixed-type phaeochromocytoma. AADC and DBH were present universally in all functioning and non-functioning tumours, including TH-negative tumours. TH is a rate-limiting enzyme of catecholamine biosynthesis and deficiency of TH is an important feature of extra-adrenal non-functioning phaeochromocytomas.

Adrenal Gland Neoplasms↗
PubMed2026

The metastatic spectrum in functional and non-functional NENs: mechanistic insights from multi-omics.

Neuroendocrine neoplasms (NENs) are biologically heterogeneous tumors in which differentiation/grade and hormonal functionality are intersecting but non-equivalent axes. This review focuses on functional and non-functional well-differentiated neuroendocrine tumors (NETs), principally gastroenteropancreatic and pancreatic NETs, and critically evaluates how site, lineage, stage, tumor burden, genomic and epigenetic alterations, immune-stromal remodeling, metabolic adaptation, microbiome-associated signals, and treatment pressure converge on metastasis and recurrence. Apparent outcome differences by functionality are inconsistent after clinicopathological adjustment: non-functional presentation is often enriched for delayed diagnosis and adverse features, whereas functional subtypes range from typically indolent insulinomas to clinically aggressive hormone-producing tumors. We reconcile these observations through a layered model in which lineage-defining alterations and chromatin/telomere programs establish cellular state; signaling and metabolic plasticity enable stress adaptation; and hypoxia, angiogenesis, immune cells, fibroblasts, extracellular matrix, and therapy create selective niches for dissemination and relapse. We also define computational strategies for heterogeneous multi-omics integration and a staged biomarker-validation pathway. Evidence remains dominated by pancreatic NETs, and causal support is weakest for microbiome-functionality relationships and several proposed cross-omic links. A spectrum-based framework is therefore most useful when it generates testable, site- and grade-specific hypotheses rather than treating functionality as an isolated prognostic variable.

Humans↗
PubMed1979

Impaired left ventricular function in chronic aortic valve disease: survival and function after replacement by Björk-Shiley prosthesis.

Postoperative survival and left ventricular function were studied in 128 patients who underwent isolated aortic valve replacement by the Björk-Shiley valve between 1973 and 1977. The average follow-up was 2.1 years. Patients with associated coronary artery disease or mitral valve disease were excluded. Preoperative ejection fraction ranged from 15-84%. Forty-two patients were restudied by cardiac catheterization 9.1 +/- 1.1 months (mean +/- SEM) after valve replacement. The hospital mortality was 11%. Preoperative type of valve lesion, functional class, cardiothoracic ratio, and ejection fraction (EF) had no significant effect on postoperative survival up to 4 years. After operation, left ventricular mass (LVMI) and peak systolic wall stress (PSWS) fell significantly, while EF and mean normalized systolic ejection rate (MNSER) increased in aortic stenosis and in aortic insufficiency. Neither in aortic stenosis nor in aortic insufficiency was there a significant relation between preoperative ejection fraction and postoperative LVMI, EF, MNSER and PSWS. We attributed this to a marked improvement of left ventricular function in patients with preoperative impaired ventricular function. Six patients with paravalvular leak to restudy has a significantly lower EF and MNSER, and a higher PSWS than patients without leak. Patients without leak had normal EF, MNSER and PSWS when compared with 10 normal persons, but LVMI remained moderately elevated. Postoperative transprosthetic gradient was 11.9 mm Hg (range 0-64 mm Hg). We conclude that impaired cardiac function is completely restored after aortic valve replacement by Björk-Shiley valve, if valve function is good. Patients with impaired cardiac function preoperatively did not have a poorer prognosis after operation than patients with normal function.

Adolescent↗
PubMed1977

Differentiation of functionally active mouse T-lymphocytes from functionally inactive bone marrow precursors.

An investigation has been made of the development of various T cell functions in lethally irradiated mice reconstituted with anti-0 treated spleen or bone marrow cells. Evidence is presented to show that both organs contain a post-thymic precursor pool able to regenerate by 15 days limited T cell responses in thymectomized recipients. A prethymic pool also exists in each organ able to regenerate, at a later date, first a suppressor T cell population and probably later, mature functional T cells involved in helper functions and cell mediated lympholysis. The spleen is apparently a better source of precursors of the suppressor cells than bone marrow, while a poorer source of precursors of the other T cell functions. All T cell functions investigated apparently first appear in large cells which undergo a reversion to small cells without necessarily maturing to their full potential reactivity. By following the kinetics of appearance of T cell functions, and the physical parameters of the cells with which these functions are associated, it is shown that PHA responding and Con A responding cells, cytotoxic T cell progenitors, helper T cells for antibody production and helper T cells for cytotoxicity induction can all at some stage of differentiation be separated from one another.

Animals↗
PubMed1976

Renal function in experimental chronic hydronephrosis. III. Glomerular and tubular functions in relation to renal pelvic volume.

Studies of renal function comprising determination of exogenous creatinine clearance, urinary osmolality and TmG were performed on 23 dogs, for each kidney separately, after hydronephrosis with partial ureteric obstruction had been produced by ligation of one ureter over an indwelling catheter. A method for determining the volume of the hydronephrotic renal pelvis was developed and the degree of functional reduction was correlated to the degree of pelvic dilatation. In 11 cases the renal blood flow was determined by direct measurement. Statistically significant reductions of the glomerular and tubular functions were noted on the hydronephrotic side. TmG and the urinary osmolality showed the greatest percentual decreases and the TmG/GFR ratio the smallest. The decrease in this ratio was due to greater deterioration of tubular than of glomerular function. The renal blood flow was reduced on the hydronephrotic side in comparison with the intact side, but seemed relatively less affected than the glomerular and tubular functions. Compensation by the intact kidney resulted in masking of the deterioration on the hydronephrotic side; thus for the whole material the mean GFR and urinary osmolality for the two kidneys together remained essentially unchanged. No statistically significant correlation between the degree of functional reduction and the degree of pelvic dilatation was found. Such a correlation could therefore not be used in the individual case as an indication of the functional capacity of a kidney.

Animals↗
PubMed1979

Differentiation of functionally active mouse T lymphocytes from functionally inactive bone marrow precursors. IV. Recovery of T-cell function from bone marrow precursors in a histo-incompatible environment.

Regeneration of T-cell activities in vivo or in vitro from mouse bone marrow precursors differentiating in the presence of an allogeneic thymus was investigated. The data indicated that T-depleted bone marrow cells fail to affect long-term reconstitution of allogeneic recipients unless a pool of rapidly maturing T-precursor cells is also removed (post-thymic pool). Animals reconstituted with pre-thymic bone marrow stem cells become stable chimaeras in which cells capable of generating an in vitro CML response to host antigens, as well as cells capable of suppressing that response, could be demonstrated. Similar data (CML directed against the H-2 antigens of the 'host' thymus feeder layer and cells capable of inhibiting that response) were obtained when pre-thymic bone marrow cells were grown in vitro on allogeneic thymus feeder cells. When cytotoxic T-lymphocyte precursor (CTLp) and helper (CTLh) cells were separately investigated, a restriction in their co-operation for an anti-host response was observed when precursor cells differentiated in an allogeneic environment. Only CTLp and CTLh differentiating in the presence of the same allogeneic thymus source (whether in vivo or in vitro) could co-operate to generate CTL directed to H-2 antigens of that thymus source.

Animals↗
PubMed1977

Relation of immediate post-transplant renal function to long-term function in cadaver kidney recipients.

Renal function studies 12 to 41 months after transplantation have been performed on seven cadaver renal allograft recipients who demonstrated immediate primary function after transplant (group A) and seven similar recipients who had delayed primary function (group B). The groups were matched as closely as possible for major physical characteristics and their postoperative management; in particular, only one patient had a post-transplant renal biopsy. Glomerular filtration rate was determined by 24-hr creatinine clearance, endogenous creatinine clearance, and inulin clearance was usually lower in those patients having delayed primary function and they excreted more glucose per 24 hr and reabsorbed a smaller proportion of the filtered glucose load under infusion conditions. These results are discussed in relation to the effect of immediate and delayed primary function on the long-term prognosis of such patients.

Adult↗
PubMed2026

Structural modeling and functional characterization of a novel gain-of-function TLR8 variant causing severe inflammatory syndrome.

With the increasing use of genetic sequencing to investigate inborn errors of immunity, rare variants are frequently identified, yet their clinical relevance often remains uncertain. Establishing pathogenicity requires a multidisciplinary approach that integrates genetic, structural, functional, and clinical data. Here, we used such a strategy to investigate a previously unreported hemizygous missense variant - alanine (A) to threonine (T) at residue 518 - in Toll-like receptor 8 (TLR8), identified in 2 male siblings with recurrent infections and systemic inflammation, characterized by a proinflammatory immune signature and B cell dysregulation. Functional studies showed that the TLR8 A518T variant enhanced NF-κB activation and increased secretion of proinflammatory cytokines compared with WT TLR8 upon stimulation, consistent with a gain-of-function effect. Protein degradation and turnover assays revealed reduced abundance of the mutant TLR8 protein due to faster turnover and increased proteasomal degradation. Computational modeling predicted enhanced structural stabilization of the active TLR8 homodimer interface via additional water-mediated hydrogen bonds introduced by the A518T substitution. Together, these findings integrating structural modeling with functional assays identify a novel TLR8 ligand-specific gain-of-function mutation resulting in complex immunopathology in 2 siblings.

Humans↗
PubMed1978

Experimental evolution of a new enzymatic function. II. Evolution of multiple functions for ebg enzyme in E. coli.

The evolution of ebgo enzyme of Escherichia coli, an enzyme which is unable to hydrolyze lactose, lactulose, lactobionate, or galactose-arabinoside effectively, has been directed in successive steps so that the evolved enzyme is able to hydrolyze these galactosides effectively. I show that in order for a strain of E. coli with a lacZ deletion to evolve the ability to use lactobionate as a carbon source, a series of mutations must occur in the ebg genes, and that these mutations must be selected in a particular order. The ordered series of mutations constitutes an obligatory evolutionary pathway for the acquisition of a new function for ebgo enzyme. A comparison of newly evolved strains with parental strains shows that when ebg enzyme acquires a new function, its old functions often suffer; but that in several cases old functions are either unaffected or are improved. I conclude that divergence of functions catalyzed by an enzyme need not require gene duplication.

Biological Evolution↗
PubMed1975

Bacteriophage P22 virion protein which performs an essential early function. II. Characterization of the gene 16 function.

P16 is a virion protein and, as such, is incorporated into the phage head as a step in morphogenesis. The role of P16 in assembly is not essential since particles are formed without this protein which appear normal by electron microscopy. P16 is essential when the particle infects a cell in the following cycle of infection. In the absence of functional P16, the infection does not appear to proceed beyond release of phage DNA from the capsid. No known genes are expressed, no DNA is transcribed, and the host cell survives the infection, continuing to grow and divide normally. The P16 function is required only during infection for the expression of phage functions. Induction in the absence of P16 proceeds with the expression of early and late genes and results in particle formation. P16 must be incorporated during morphogenesis into progeny particles after both infection and induction for the progeny to be infectious. The P16 function is necessary for transduction as well as for infection. Its activity is independent of new protein synthesis and it is not under immunity control. P16 can act in trans, but appears to act preferentially on the phage or phage DNA with which it is packaged. The data from complementation studies are compatible with P16 release from the capsid with the phage DNA. In the absence of P16 the infection is blocked, but the phage genome is not degraded. The various roles which have been ruled out for P16 are: (i) an early regulatory function, (ii) an enzymatic activity necessary for phage production, (iii) protection of phage DNA from host degradation enzymes, (iv) any generalized alteration of the host cell, (v) binding parental DNA to the replication complex, and (vi) any direct involvement in the replication of P22 DNA. P16 can be responsible for: (i) complete release of the DNA and disengagement from the capsid, (ii) bringing the released DNA to some necessary cell site or compartment such as the cytoplasm, (iii) removal of other virion proteins from the injected DNA, and (iv) alterations of the structure of the injected DNA.

Adsorption↗
PubMed1978

Obesity and thyroid function. 3. Relationship between some indicators of thyroid function and the energy metabolism of striated muscle in obese women.

1. In a group of 23 obese women the relations between some indicators of thyroid function (thyroxine-binding globuline--T4BG, triiodothyronine-binding globuline--T3BG, Achilles tendon reflex--ART) on the one hand and activities of enzymes of the energy metabolism (hexokinase--HK, triose phosphate dehydrogenase--TPDH, lactate dehydrogenase--LDH, glycerol-3-phosphate dehydrogenase--GPDH, citrate synthease--CS, malate dehydrogenase--MDH, hydroxyacyl--COA dehydrogenase) in the quadriceps femoris muscle on the other hand were investigated. 2. Correlations were found between T4BG and TPDH, LDH and GPDH activities, between T3BG and TPDH and GPDH activities and between the value of the Achilles tendon reflex and TPDH activity. Functionally these enzymes activities are associated with glycolysis and hydrogen transport from cytoplasmatic NADH2. No correlations were found between enzymes of the aerobic metabolism incl. enzymes of fatty acid oxidation and indicators of thyroid function. 3. The results indicate a relationship between thyroid function and enzymes involved in glycolysis and hydrogen transport from cytoplasmatic NADH2. They do not suggest, however, the unequivocal conclusion that in obese women with reduced thyroid function there is a generally reduced energy supplying metabolism in skeletal muscle.

Achilles Tendon↗
PubMed1978

Adherent cell function in murine T lymphocyte antigen recognition. II. Definition of genetically restricted and nonrestricted macrophage functions in T cell proliferation.

The mechanisms by which adherent cells, presumably of mononuclear phagocytic lineage, influence in vitro antigen-specific activation of murine T lymphocytes was examined. Two distinct functions for macrophages could be discerned. One macrophage function is dependent on a soluble factor produced by cultured adherent cells and is most easily studied with complex multideterminant antigens. This factor is neither antigen-specific nor MHC-restricted in its action in that PEC, regardless of haplotype, produce factor in the absence of antigen. A second function, antigen-specific T cell activation, is seen when antigens of more restricted heterogeneity are used, such as those under the control of Ir genes. This latter activity demands identity or partial identity between the antigen-presenting cell and the primed T cell, thus suggesting an additional specific, genetically restricted function for macrophages in in vitro antigen recognition. Whether these adherent cell functions are mediated by all or distinct subsets of cells was not established.

Animals↗
PubMed1977

Clinical significance of pulmonary function tests. Pulmonary function after uncomplicated myocardial infarction.

Derangement of pulmonary function following myocardial infarction is related to the severity of hemodynamic dysfunction. Abnormalities of pulmonary function appear even in patients without clinical or radiologic evidence of congestive failure. There is a reduction in vital capacity and rates of air flow. There is evidence for dysfunction of "small airways" and diminished ventilation to dependent parts of the lung. Total lung capacity may be normal or reduced, and residual volume may be increased slightly in uncomplicated myocardial infarction. Residual volume falls with more pronounced pulmonary congestion and edema. Distribution of pulmonary perfusion is altered after myocardial infarction, with a shift of perfusion away from the dependent parts of the lung (bases) towards the apices. Pulmonary gas exchange is impaired, with hypoxemia (due to both ventilation-perfusion inequality and increased shunting); and the diffusing capacity for carbon monoxide is diminished. Dead space is increased. The basic pathophysiologic mechanism responsible for abnormalities of pulmonary function is increased pulmonary water, which may be very minimal with uncomplicated myocardial infarction and stay primarily in the pulmonary interstitial space, but becomes progressively more severe with eventual alveolar flooding and marked impairment of pulmonary function.

Humans↗
PubMed1977

Kinetics of hepatocellular proliferation as a function of the microvascular structure and functional state of the liver.

An analysis of hepatocellular proliferation in regenerating rat liver reveals a dependence of kinetic parameters on the microvascular structure of the liver. Influx kinetics of hepatocytes into DNA synthesis as well as cell cycle phases vary in different parts of the liver lobule between the afferent and efferent vascular poles. Heterogeneity of the proliferative response and size limitations on cell cycle compartments appear to be intimately related to the actual functional state of the individual liver cell. Modifications of liver cell functions result in variations of the proliferative activity. Phenobarbital-induced hypertrophy of hepatocytes reveals a permissive action on G1- S influx. Selective destruction of the subpopulations, by allyl formate, leads to a new functional determination of the residual liver and to a change in proliferative compartments. Maximum modulation of cell cycle compartments is obtained by hydroxyurea-induced synchronization of hepatocytes after partial liver resection. During hydroxyurea treatment, the regenerating liver shows a pronounced cellular hypertrophy. After release from hydroxyurea block, cells embark on DNA synthesis simultaneously. The DNA synthesizing compartment comprises almost the entire liver cell population. Heptotrophic factors might play a part in regulating or modifying hepatocellular function and proliferative response after cell loss.

Allyl Compounds↗