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PubMed2026

Microbial and functional shifts between flare and remission in a single-center cohort of children with inflammatory bowel disease.

BACKGROUND: Gut microbial dysbiosis is central to the pathogenesis of inflammatory bowel disease (IBD). While gut microbiome differences between patients with and without IBD are well established, microbiome changes associated with disease activity and remission remain limited, particularly in paediatric populations. AIM: To examine intra-individual taxonomic and functional gut microbiome changes during transition from active flare to remission under maintenance immunosuppression in a pilot single-center Singapore cohort of children with IBD. METHODS: Paired stool samples and clinical data were collected from seven patients with paediatric IBD [5 Crohn's disease (CD), 2 ulcerative colitis; ≤ 18 years] during active disease/flare (visit 1; Pediatric CD Activity Index/Pediatric Ulcerative Colitis Activity Index ≥ 10) and subsequent clinical remission (visit 2; Pediatric CD Activity Index/Pediatric Ulcerative Colitis Activity Index < 10). Samples underwent shotgun metagenomic sequencing for high-resolution taxonomic profiling and functional annotation of Kyoto Encyclopaedia of Genes and Genomes pathways. RESULTS: Gut microbial diversity was reduced during flare compared to remission, with Actinobacteria abundance significantly higher in remission. Two distinct microbial clusters differentiated flare and remission states: The remission cluster was enriched with Bifidobacterium adolescentis, Bifidobacterium dentium, Lactobacillus gasseri, Faecalibacterium prausnitzii, while the flare state showed increased Klebsiella pneumoniae. Remission was further characterized by a downregulation of pathogenic microbes and an upregulation of beneficial microbes including a higher abundance of the butyrate producer Anaerostipes hadrus (P = 0.046). Microbial functional genes enriched in remission were predominantly associated with metabolic pathways including vitamin and cofactor biosynthesis, as well as carbohydrate, amino acid, and lipid metabolism. CONCLUSION: The transition from flare to remission in Singaporean children with IBD is characterized by functional remodeling of the gut microbiome, which may contribute to recovery processes related to intestinal barrier integrity, cellular maintenance, and tissue repair. Targeted modulation of the gut microbiome may help sustain remission in paediatric IBD.

Functional shift↗

PubMed2004

Systematic quantification of gene interactions by phenotypic array analysis.

A phenotypic array method, developed for quantifying cell growth, was applied to the haploid and homozygous diploid yeast deletion strain sets. A growth index was developed to screen for non-additive interacting effects between gene deletion and induced perturbations. From a genome screen for hydroxyurea (HU) chemical-genetic interactions, 298 haploid deletion strains were selected for further analysis. The strength of interactions was quantified using a wide range of HU concentrations affecting reference strain growth. The selectivity of interaction was determined by comparison with drugs targeting other cellular processes. Bio-modules were defined as gene clusters with shared strength and selectivity of interaction profiles. The functions and connectivity of modules involved in processes such as DNA repair, protein secretion and metabolic control were inferred from their respective gene composition. The work provides an example of, and a general experimental framework for, quantitative analysis of gene interaction networks that buffer cell growth.

Cluster Analysis↗

PubMed2000

Cold acclimation or grapeseed oil feeding affects phospholipid composition and mitochondrial function in duckling skeletal muscle.

The phospholipid fatty acid (FA) composition and functional properties of skeletal muscle and liver mitochondria were examined in cold-acclimated (CA, 4 degrees C) ducklings. Phospholipid FA of isolated muscle mitochondria from CA birds were longer and more unsaturated than those from thermoneutral (TN, 25 degrees C) reared ducklings. The rise in long-chain and polyunsaturated FA (PUFA, mainly 20:4n-6) was associated with a higher State 4 respiration rate and a lower respiratory control ratio (RCR). Hepatic mitochondria, by contrast, were much less affected by cold acclimation. The cold-induced changes in phospholipid FA profile and functional properties of muscle mitochondria were reproduced by giving TN ducklings a diet enriched in grapeseed oil (GO, rich in n-6 FA), suggesting a causal relationship between the membrane structure and mitochondrial functional parameters. However, hepatic mitochondria from ducklings fed the GO diet also showed an enrichment in long-chain PUFA but opposite changes in their biochemical characteristics (lower State 4, higher RCR). It is suggested that the differential modulation of mitochondrial functional properties by membrane lipid composition between skeletal muscle and liver may depend on muscle-specific factors possibly interacting with long-chain PUFA and affecting the proton leakiness of mitochondrial membranes.

Animals↗

PubMed1989

Whole blood aggregation using impedance and particle counter methods.

Platelet function in platelet-rich plasma may be evaluated using an optical or electrical impedance method. Platelet function in whole blood may be studied using an impedance or particle counter method. A comparison of these techniques in whole blood has not been performed. Twenty-four healthy subjects were studied using both techniques over a range of concentrations of collagen and adenosine diphosphate (ADP). Although broad similarities exist, discordant patterns occur in individual subjects. The particle counter method is capable of detecting small aggregates and thus is more sensitive. The impedance aggregometer detects only larger aggregate formation. These techniques are complementary rather than competitive and may have considerable potential in profiling platelet function.

Adenosine Diphosphate↗

PubMed1985

Calcium antagonists and myocardial protection: a comparative study of the functional, metabolic and electrical consequences of verapamil and nifedipine as additives to the St. Thomas' cardioplegic solution.

Using an isolated rat heart preparation as a model of cardiopulmonary bypass and ischemic arrest, a comparative study has been undertaken in order to characterize the functional, metabolic and electrophysiological consequences resulting from the addition of dl-verapamil or nifedipine to the St. Thomas' Hospital cardioplegic solution. Hearts (n = 6 in each group) were subjected to cardioplegic infusion with the St. Thomas' solution with or without added verapamil (1.1 micromoles/liter) or nifedipine (0.075 micromoles/liter). After 35 minutes of normothermic (37 degrees C) ischemic arrest, reperfusion was initiated and functional recovery was measured and expressed as a percent of its pre-ischemic control value. Inclusion of nifedipine in the cardioplegic solution improved the post-ischemic recovery of cardiac output from its control value of 59.8 +/- 3.0% to 80.0 +/- 2.5%. The temporal characteristics for the post-ischemic recovery of electrical activity and contractile performance were uncomplicated and similar to control hearts. Inclusion of verapamil also improved the protective properties of the St. Thomas' solution with cardiac output recovering to 76.8% +/- 2.8%. However, in contrast to the control and nifedipine groups, the profile for functional recovery was complex. After an early initial recovery, pressure development declined for 0.5 to 6.0 minutes. This occurred despite the recovery of electrical activity. Hearts then exhibited a second phase of recovery where pressure development returned to normal and this was sustained for the duration of the experiment. Analysis of electrocardiographic characteristics revealed a significant prolongation of the P-P and P-Q interval during the first 10 minutes of reperfusion in the verapamil group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Effects of oral cisapride on interdigestive jejunal motor activity, psychomotor function, and side-effect profile in healthy man.

Intravenous cisapride was shown to induce a phase-2-like pattern of human interdigestive jejunal motor activity containing an increased number of propagated contractions. This study investigated the effects of oral cisapride in 12 fasting healthy males. Jejunal pressures were recorded by a pneumohydraulic system and five catheter orifices positioned 10-30 cm aborad the ligament of Treitz. Single oral doses of 5 and 10 mg cisapride, administered 5 min after an activity front under random double-blind conditions, induced a phase-2-like jejunal motor pattern with a significantly higher number and amplitude of contractions and significantly more aborally propagated waves than placebo (P less than 0.001), while the number of subjects with activity fronts decreased with increasing dose. Five and 10 mg cisapride administered tid for three days affected psychomotor function, subjective feelings, and side-effect frequency, apart from increases in systolic blood pressure and heart rate, no more than placebo. It is concluded that in fasting man, oral cisapride induces a highly propagative phase-2-like jejunal motor pattern causing only minor side effects.

Administration, Oral↗

PubMed2001

Characteristics of healthy population among the migrants to the North.

The goal of the study was to elucidate psychophysiological characteristics of subjects who can adapt effectively to Arctic and Subarctic conditions. Plasma cortisol and insulin levels, blood pressure as well as functional sensori-motor asymmetry have been examined in the groups of North Selkups and transit workers from the Subarctic regions. The highest level of plasma cortisol was observed in the Selkups with the predominance of the right indices of sensorimotor asymmetry, whereas the lowest cortisol concentrations have been found in the left-handed groups. The level of insulin appeared to be lower in all examined groups of the Selkups. No changes in the blood pressure were found among the northern populations. The maximum incidence of arterial hypertension was revealed among shift workers with the predominance of the right profile of functional asymmetry. The indices of functional asymmetry, giving important information about adaptive abilities of different populations to severe climato-geographical conditions, can be a useful prognostic factor for the professional selection of workers in the North regions.

Adaptation, Physiological↗

PubMed2000

Cloning and functional expression of a human orthologue of rat vanilloid receptor-1.

Capsaicin, resiniferatoxin, protons or heat have been shown to activate an ion channel, termed the rat vanilloid receptor-1 (rVR1), originally isolated by expression cloning for a capsaicin sensitive phenotype. Here we describe the cloning of a human vanilloid receptor-1 (hVR1) cDNA containing a 2517 bp open reading frame that encodes a protein with 92% homology to the rat vanilloid receptor-1. Oocytes or mammalian cells expressing this cDNA respond to capsaicin, pH and temperature by generating inward membrane currents. Mammalian cells transfected with human VR1 respond to capsaicin with an increase in intracellular calcium. The human VR1 has a chromosomal location of 17p13 and is expressed in human dorsal root ganglia and also at low levels throughout a wide range of CNS and peripheral tissues. Together the sequence homology, similar expression profile and functional properties confirm that the cloned cDNA represents the human orthologue of rat VR1.

Amino Acid Sequence↗

PubMed1997

A prediction model for functional recovery in stroke.

BACKGROUND AND PURPOSE: Stroke-related physical disability can diminish quality of daily living, place care burden on families, and increase need for long-term institutionalization. We developed a prognostic index for use in research and with potential for adaptation to clinical practice that establishes the likelihood of an individual achieving a specific stage of functional recovery after stroke rehabilitation. METHODS: We constructed the index using logistic regression based on 3760 patient records from 96 rehabilitation facilities in 31 states. The stage, as measured by the Functional Independence Measure, includes achievement of the following: independence in eating, grooming, and dressing the upper body; continence in bowel and bladder; and transfer between a bed and chair with supervision only. RESULTS: This stage was achieved by 26.1% of patients functioning below it at rehabilitation admission. Disability onset of less than 60 days was associated with more than a 3-fold increase in the likelihood of achieving the stage (adjusted odds ratio, 3.5; 95% confidence interval, 2.0 to 6.0). Each eight-point increase in an eight-item activities of daily living score, measured at admission to rehabilitation, increased the odds 2.5-fold (95% confidence interval, 2.3 to 2.8). For those living alone or employed before the stroke, the odds of achieving the stage increased by factors of 1.3 and 2.2, respectively. The index showed minimal shrinkage on cross validation. The achievement of this profile of function is important because 95.3% of stroke patients who achieved or exceeded it were discharged home, as opposed to only 66.8% of those who did not achieve it. CONCLUSIONS: The index can be used to establish prognoses for individual stroke patients at admission to rehabilitation with regard to achieving this stage. Achievement of the stage is associated with a high likelihood of discharge to home.

Activities of Daily Living↗

PubMed1994

Laterality of theta waves recorded from the bilateral hippocampi in freely moving male rats.

The correlation of rhythmic slow activity (RSA, "theta rhythm") of the rat hippocampus with voluntary movement is well known. However, it is not clear whether there is any difference between the right and left hippocampal function, and profiles of each electroencephalogram (EEG) in the rat. We fixed two paired chronically indwelling electrodes in the bilateral hippocampi, bilaterally enclosing the dorso-ventral structure. It was demonstrated that the distribution of the EEG frequency from the right ventral hippocampus was not the same as that on the other side when the rats were walking in an open area as a novelty environment. Morphological investigation suggested that there was no symmetry in structure between the right and left hippocampi in the rat. In the present investigation, bilateral hippocampal EEGs were also not identical. It is assumed that the left and right hippocampi have different functions in the rat.

Animals↗

PubMedDate not supplied

Effects of weight loss after biliopancreatic diversion on metabolism and cardiovascular profile.

BACKGROUND: Obesity is associated with increased prevalence of cardiovascular risk factors. Biliopancreatic diversion (BPD) for morbid obesity has been reported to produce anemia and malnutrition in short-term follow-up. The aim of our study was to analyze the effect of weight reduction on cardiovascular profile, renal function and nutritional status. METHODS: 35 morbidly obese patients underwent BPD. We analyzed the presence of cardiovascular risk factors, renal status, proteinuria and nutritional status before and 1 year after BPD. RESULTS: Excess weight loss was 67% at 1 year after BPD. All cardiovascular risk factors (hypertension, diabetes, hyperlipidemia) improved during follow-up. We could not find any relevant signs of malnutrition in the patients. Microalbuminuria decreased and proteinuria disappeared after weight loss. We observed less urinary calcium and citrate excretion, with an increase in oxaluria, but these changes did not increase the incidence of renal stones. CONCLUSIONS: BPD was followed by improved cardiovascular profile and a lower pro-inflammatory state. BPD did not produce significant malnutrition, anemia or renal stone disease.

Adult↗

PubMed2000

Cerebral correlates of psychotic symptoms in Alzheimer's disease.

BACKGROUND: Psychotic symptoms are produced by distributed neuronal dysfunction. Abnormalities of reality testing and false inference implicate frontal lobe abnormalities. OBJECTIVES: To identify the functional imaging profile of patients with Alzheimer's disease manifesting psychotic symptoms as measured by single photon emission computed tomography (SPECT). METHODS: Twenty patients with Alzheimer's disease who had SPECT and clinical evaluations were divided into two equal groups with similar mini mental status examination (MMSE), age, sex, and the range of behaviours documented by the neuropsychiatric inventory (NPI), except delusions and hallucinations. SPECT studies, registered to a probabilistic anatomical atlas, were normalised across the combined group mean intensity level, and subjected to a voxel by voxel subtraction of the non-psychotic minus psychotic groups. Subvolume thresholding (SVT) corrected random lobar noise to produce a three dimensional functional significance map. RESULTS: The significance map showed lower regional perfusion in the right and left dorsolateral frontal, left anterior cingulate, and left ventral striatal regions along with the left pulvinar and dorsolateral parietal cortex, in the psychotic versus non-psychotic group. CONCLUSION: Patients with Alzheimer's disease who manifest psychosis may have disproportionate dysfunction of frontal lobes and related subcortical and parietal structures.

Alzheimer Disease↗

PubMed1984

[Urethral pressure profile in sling operations for stress incontinence].

Abdominovaginal sling procedures are one of the operative methods for treating urinary stress incontinence in women. They are used especially in incontinence associated with severe pelvic floor weakness. By suspending the vesicourethral junction to the anterior abdominal wall by help of a dural or fascial sling, the bladder neck and proximal urethra are restored to their original anatomical position. Changes in intraabdominal pressure are transmitted equally to both bladder and urethra. One of the difficulties during the course of the operation is to maintain proper tension to the sling while suturing it to the rectus sheath. If the sling is placed to loosely, therapeutic failure may result; on the other hand, overtightening of the sling can lead to delayed voiding and retention of urine. With this problem in mind, urethral pressure recordings were performed during the course of 14 abdominovaginal sling operations. Significant changes concerning the functional urethral profile length, the maximum urethral pressure, and especially the shape of the urethral closure pressure profile could be demonstrated following the main operative steps.

Female↗

PubMed1990

Food proteins and maturation of small intestinal microvillus membranes (MVM). III. Food protein binding and MVM proteins in rats from newborn to young adult age.

To investigate postnatal maturational profiles of functional and biochemical properties of rat small intestinal microvillus membranes (MVM), we did a longitudinal study in rats from birth to the age of 12 weeks. In parallel, we studied binding of cow's milk proteins and of the wheat gliadin peptide B 3142, as well as MVM proteins (SDS-PAGE). Changes in MVM fluidity and lipid composition exhibited early (0-4 weeks) and intermediate and late (6-12 weeks) patterns, as has been published earlier. Postnatal changes of food protein and peptide binding occurred early during the observation period, not related to weaning. There was not much further change in binding after 6-8 weeks. Developmental profiles of MVM protein and some lipid changes resembled, but did not equal, changes in food protein binding. We conclude that changes in MVM biochemical composition affect MVM binding characteristics. In particular, high molecular weight MVM proteins (susceptible to trypsin treatment) appear to play a role in postnatal maturational differences in MVM food protein binding.

Aging↗

PubMed2004

Fat supplementation and reproduction in beef females.

Inadequate dietary energy intake and poor body condition can negatively affect reproductive function. Supplemental lipids have been used to increase energy density of the diet and may also have direct positive effects on reproduction in beef cattle. Several fatty acid sources have been studied as they relate to reproductive function. Common sources include sunflower, safflower, cottonseed, rice bran, soybeans, fishmeal, animal tallow, and calcium salts of fatty acids. Fats have been fed before and after calving, during the breeding season, and during heifer development. Response to fat has been investigated through measuring body weight and body condition score, age at puberty, postpartum interval, first-service conception rates, pregnancy rates, calving interval, calving difficulty, and calf birth and weaning weight. Animal response seems to depend on body condition score, age (parity), nutrients available in the diet, and type of fat supplemented. To elucidate potential mechanisms of action, scientists have investigated changes in follicular and uterine development, hormonal profiles, brain function, and embryonic development. Feeding supplemental fat has resulted in varied and inconsistent effects on reproductive function. Elucidating how supplemental fat can influence reproductive function has been a difficult process. The complexity of the reproductive system and makeup of fat supplements are often confounded by management conditions and forage quality both in research and commercial feeding situations.

Animals↗

PubMed1999

Motor-learning-related changes in piano players and non-musicians revealed by functional magnetic-resonance signals.

In this study, we investigated blood-flow-related magnetic-resonance (MR) signal changes and the time course underlying short-term motor learning of the dominant right hand in ten piano players (PPs) and 23 non-musicians (NMs), using a complex finger-tapping task. The activation patterns were analyzed for selected regions of interest (ROIs) within the two examined groups and were related to the subjects' performance. A functional learning profile, based on the regional blood-oxygenation-level-dependent (BOLD) signal changes, was assessed in both groups. All subjects achieved significant increases in tapping frequency during the training session of 35 min in the scanner. PPs, however, performed significantly better than NMs and showed increasing activation in the contralateral primary motor cortex throughout motor learning in the scanner. At the same time, involvement of secondary motor areas, such as bilateral supplementary motor area, premotor, and cerebellar areas, diminished relative to the NMs throughout the training session. Extended activation of primary and secondary motor areas in the initial training stage (7-14 min) and rapid attenuation were the main functional patterns underlying short-term learning in the NM group; attenuation was particularly marked in the primary motor cortices as compared with the PPs. When tapping of the rehearsed sequence was performed with the left hand, transfer effects of motor learning were evident in both groups. Involvement of all relevant motor components was smaller than after initial training with the right hand. Ipsilateral premotor and primary motor contributions, however, showed slight increases of activation, indicating that dominant cortices influence complex sequence learning of the non-dominant hand. In summary, the involvement of primary and secondary motor cortices in motor learning is dependent on experience. Interhemispheric transfer effects are present.

Adult↗

PubMed1994

Developmental and regional expression in the rat brain and functional properties of four NMDA receptors.

An in situ study of mRNAs encoding NMDA receptor subunits in the developing rat CNS revealed that, at all stages, the NR1 gene is expressed in virtually all neurons, whereas the four NR2 transcripts display distinct expression patterns. NR2B and NR2D mRNAs occur prenatally, whereas NR2A and NR2C mRNAs are first detected near birth. All transcripts except NR2D peak around P20. NR2D mRNA, present mainly in midbrain structures, peaks around P7 and thereafter decreases to adult levels. Postnatally, NR2B and NR2C transcript levels change in opposite directions in the cerebellar internal granule cell layer. In the adult hippocampus, NR2A and NR2B mRNAs are prominent in CA1 and CA3 pyramidal cells, but NR2C and NR2D mRNAs occur in different subsets of interneurons. Recombinant binary NR1-NR2 channels show comparable Ca2+ permeabilities, but marked differences in voltage-dependent Mg2+ block and in offset decay time constants. Thus, the distinct expression profiles and functional properties of NR2 subunits provide a basis for NMDA channel heterogeneity in the brain.

Animals↗

PubMed1984

Monoclonal antibodies as functional probes of the HN glycoprotein of Newcastle disease virus: antigenic separation of the hemagglutinating and neuraminidase sites.

A panel of nine monoclonal antibodies has been used to construct a functional inhibition profile of four antibody-binding sites previously delineated on the HN glycoprotein of Newcastle disease virus. Antibodies to all four sites are capable of neutralizing infectivity and inhibiting hemolysis and neuraminidase activity with fetuin. There is a good correlation between the fractions of infectivity and neuraminidase activity which survive antibody treatment. However, the inhibition of hemolysis is in the inverse relative order of the neutralization of infectivity. Antibodies to sites 1 and 2 are capable of inhibiting hemagglutination, whereas only antibodies to site 2 can inhibit neuraminidase activity on the smaller substrate N-acetyl neuraminlactose. This antigenically separates the hemagglutinin and neuraminidase sites on the HN glycoprotein. We used these functional inhibition studies to speculate about the location of the four antigenic sites relative to the hemagglutinin and neuraminidase sites.

Animals↗