Anterior capsular phimosis with complete occlusion of the capsulorhexis opening.
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Aged, 80 and over↗
Biomedical subjects
R Calvert
Publications and source records attributed to R Calvert.
Health status of children with moderate to severe cerebral palsy.
The aim of the study was to evaluate the health of children with cerebral palsy (CP) using a global assessment of quality of life, condition-specific measures, and assessments of health care use. A multicenter population-based cross-sectional survey of 235 children, aged 2 to 18 years, with moderate to severe impairment, was carried out using Gross Motor Function Classification System (GMFCS) levels III (n = 56), IV (n = 55), and V (n = 122). This study group scored significantly below the mean on the Child Health Questionnaire (CHQ) for Pain, General Health, Physical Functioning, and Impact on Parents. These children used more medications than children without CP from a national sample. Fifty-nine children used feeding tubes. Children in GMFCS level V who used a feeding tube had the lowest estimate of mental age, required the most health care resources, used the most medications, had the most respiratory problems, and had the lowest Global Health scores. Children with the most severe motor disability who have feeding tubes are an especially frail group who require numerous health-related resources and treatments. Also, there is a relationship among measures of health status such as the CHQ, functional abilities, use of resources, and mental age, but each appears to measure different aspects of health and well-being and should be used in combination to reflect children's overall health status.
Activities of Daily Living↗
The structure of the IgE Cepsilon2 domain and its role in stabilizing the complex with its high-affinity receptor FcepsilonRIalpha.
The stability of the complex between IgE and its high-affinity receptor, FcepsilonRI, on mast cells is a critical factor in the allergic response. The long half-life of the complex of IgE bound to this receptor in situ ( approximately 2 weeks, compared with only hours for the comparable IgG complex) contributes to the permanent sensitization of these cells and, hence, to the immediate response to allergens. Here we show that the second constant domain of IgE, Cepsilon2, which takes the place of the flexible hinge in IgG, contributes to this long half-life. When the Cepsilon2 domain is deleted from the IgE Fc fragment, leaving only the Cepsilon3 and Cepsilon4 domains (Cepsilon3-4 fragment), the rate of dissociation from the receptor is increased by greater than 1 order of magnitude. We report the structure of the Cepsilon2 domain by heteronuclear NMR spectroscopy and show by chemical shift perturbation that it interacts with FcepsilonRIalpha. By sedimentation equilibrium we show that the Cepsilon2 domain binds to the Cepsilon3-4 fragment of IgE. These interactions of Cepsilon2 with both FcepsilonRIalpha and Cepsilon3-4 provide a structural explanation for the exceptionally slow dissociation of the IgE-FcepsilonRIalpha complex.
Base Sequence↗
Competition performance and basal nocturnal catecholamine excretion in cross-country skiers.
UNLABELLED: Objective techniques to determine whether an athlete is optimally prepared for a competition are virtually nonexistent. Preparedness for sports competition is commonly judged through the experience of the athletes and their coaches. Evidence from overtraining studies suggests that catecholamine (Cat) excretion rates may correlate with performance in athletes. PURPOSE: We therefore attempted to determine whether a relationship existed between performances of world-class cross-country skiers and basal nocturnal Cat excretion (BNCE). METHOD: During the Cross-Country Skiing World Championships, we determined BNCE in nine cross-country skiers of the Swiss national team by measuring free Cat concentration (dopamine = D, norepinephrine = NE, epinephrine = E) in morning urine samples, using high performance liquid chromatography. Expert judgments of competition performance (ECP) were assessed by two experienced professional coaches of the national team by using an 11-step scale. RESULTS: The BNCE correlated significantly with ECP in cross-country skiers (r2 = 0.84 and P < for NE; r2 = 0.86 and P < 0.001 for D). Athletes who had their best absolute competition results (ACR) showed the highest NE and D concentrations. CONCLUSION: These data suggest that competitive cross-country skiers with higher D and NE excretion may reach better competition levels compared with those with lower levels. Measures of BNCE provide objective information about competition performance, which may benefit athletes in their precompetition preparation.
Adult↗
Validating a practical approach to determine weight control in obese children and adolescents.
OBJECTIVE: To study the usefulness of a mathematical index for assessing changes in body composition of obese children and adolescents who undergo a weight control program. DESIGN: A short-term longitudinal (mean of 19 months) cohort study. SUBJECTS: Sixty-seven obese children and adolescents (38 M, 29 F, age 6-16 (mean 11)y) who took part in a clinic-based weight control program. MEASUREMENTS: Percentage body fat was assessed at the start of the program by underwater weighing (UWW) and by bioelectrical impedance (BIA). Response to the program was assessed by a mathematical index (MI), based on observed and expected changes in height and weight, and by changes in percentage fat as measured by BIA. RESULTS: Adiposity, as assessed by BIA at the start of the program, was highly correlated to that obtained by UWW (r = 0.96 for fat-free mass). Changes in the MI over the program were correlated fairly well (r = -0.81, SEE = 3.57 kg) with changes in percentage fat as assessed by BIA. CONCLUSION: Using change in BIA as criterion, the MI is valid for assessing changes in percentage body fat of obese children and adolescents over time. This index is of use to clinicians who lack body composition equipment and need a quick method to analyze the effectiveness of a weight control program in obese children and adolescents.
Adipose Tissue↗
Population pharmacokinetics of methadone in opiate users: characterization of time-dependent changes.
AIMS: Although methadone is widely used to treat opiate dependence, guidelines for its dosage are poorly defined. There is increasing evidence to suggest that a strategy based on plasma drug monitoring may be useful to detect non-compliance. Therefore, we have developed a population-based pharmacokinetic (POP-PK) model that characterises adaptive changes in methadone kinetics. METHODS: Sparse plasma rac-methadone concentrations measured in 35 opiate-users were assessed using the P-Pharm software. The final structural model comprised a biexponential function with first-order input and allowance for time-dependent change in both clearance (CL) and initial volume of distribution (V ). Values of these parameters were allowed to increase or decrease exponentially to an asymptotic value. RESULTS: Increase in individual values of CL and increase or decrease in individual values of V with time was observed in applying the model to the experimental data. CONCLUSIONS: A time-dependent increase in the clearance of methadone is consistent with auto-induction of CYP3A4, the enzyme responsible for much of the metabolism of the drug. The changes in V with time might reflect both up- and down-regulation of alpha1-acid glycoprotein, the major plasma binding site for methadone. By accounting for adaptive kinetic changes, the POP-PK model provides an improved basis for forecasting plasma methadone concentrations to predict and adjust dosage of the drug and to monitor compliance in opiate-users on maintenance treatment.
Adolescent↗
The pharmacokinetics of methadone in healthy subjects and opiate users.
AIMS: There is some evidence that monitoring methadone plasma concentration may be of benefit in dosage adjustment during methadone maintenance therapy for heroin (opiate) dependence. However, the kinetics of oral methadone are incompletely characterized. We attempted to describe the latter using a population approach combining intensive 57 h sampling data from healthy subjects with less intensive sparse 24 h data from opiate users. METHODS: Single oral doses of rac-methadone were given to 13 drug-naive healthy subjects (7 men and 6 women) and 17 opiate users beginning methadone maintenance therapy (13 men and 4 women). Plasma methadone concentrations were measured by h.p.l.c. Kinetic analysis was performed using the P-Pharm software. RESULTS: Comparison of kinetic models incorporating mono- or biexponential disposition functions indicated that the latter best represented the data. The improvement was statistically significant for the data from healthy subjects whether the full 57 h or truncated 24 h profiles were used (P<0.031 and P<0.024, respectively), while it was of borderline significance for the more variable data from opiate users (P=0.057) or for pooled (healthy subjects and opiate users) data (P=0.066). The population mean oral clearance of methadone was 6.9+/-1.5 s.d. l h(-1) (5.3+/-1.2 s.d. l h(-1) using 0-24 h data) in the healthy subjects. The results of separate analyses of the data from opiate users and healthy subjects were in contrast with those obtained from pooled data analysis. The former indicated a significantly lower clearance for opiate users (3.2+/-0.3 s.d. l h(-1), P<0.001); 95% CI for the difference = -3 to -6 l h(-1) and no difference in the population mean values of V/F (212+/-27 s.d. l and 239+/-121 s.d. l, P=0.15), while according to the latter analysis addiction was a covariate for V/F but not for oral clearance. A slower absorption of methadone in opiate users was indicated from the analysis of both pooled and separate data. The median elimination half-life of methadone in healthy subjects was 33-46 h depending on the method used to calculate this parameter. CONCLUSIONS: Estimates of the long terminal elimination half-life of methadone (33-46 h in healthy subjects and, possibly, longer in opiate users) indicated that accurate measurement of this parameter requires a duration of sampling longer than that used in this study. Our analysis also suggested that parameters describing plasma concentrations of methadone after a single oral dose in healthy subjects may not be used for predicting and adjusting dosage in opiate users receiving methadone maintenance therapy unless coupled with feedback concentration monitoring techniques (for example Bayesian forecasting).
Adolescent↗
Expression and turnover of an interstitial matrix component of the pericryptal sheath in neonatal mice.
The aim of the present study was to determine the expression and turnover of antigen 1/130, a component of the interstitial matrix associated with collagen fibrils in the pericryptal sheath, in neonatal mice (CD1). Anti-laminin was used as a control. Starting on day 9 after birth, monoclonal antibody 1/130 (Mab-1/130) or anti-laminin were either fed orogastrically or injected intraperitoneally twice daily for 3 days. Bound immunoglobulins were disclosed by indirect immunofluorescence at days 12, 16, 23, 30 and 40. Sections from duodenum, ileum and colon were incubated together on the same glass slide. At day 12, the levels of labelling in orogastrically fed animals with Mab-1/130 exhibited a proximo-distal gradient (duodenum>ileum>colon); labelling with anti-laminin was found in the duodenum only. In injected animals, the levels of labelling with both antibodies showed the same gradient (duodenum>ileum>colon). At day 23, Mab-1/130 was still detected in both groups in the duodenum and ileum, whereas anti-laminin was barely detectable and only in the duodenum. At day 30, in animals fed as above or injected intraperitoneally, Mab-1/130 was present in the duodenum at the bottom of the crypts; anti-laminin was completely absent. During the postnatal period, the turnover of antigen-1/130 appeared to be slow and, as the crypts elongated, the mesenchymal pericryptal sheath did not co-migrate with the epithelial cells.
Animals↗
Stability of the dystrophin rod domain fold: evidence for nested repeating units.
An examination of fragments of the human dystrophin rod domain, corresponding to a single structural repeating unit, showed that a critical chain length, defined with a precision of one residue at the C-terminal end, is required for formation of the native tertiary fold. We report here that extending the chain by six residues beyond this minimum results in a large increase in conformational stability. This is not related to a change in association state of the polypeptide. The results support the conjecture that successive repeating units in the rod domain of the spectrinlike proteins form a nested structure, in which the N-terminal part of the three-helix bundle of one repeat packs into the overlapping structure of the preceding repeat. This would be expected to affect functional characteristics related to flexibility of the dystrophin rod domain.
Amino Acid Sequence↗
Peroxisomes and peroxisomal enzymes in the human fetal small intestine.
The appearance and development of peroxisomes and the expression of their enzymes in the human fetal intestine have been investigated between 11 and 22 weeks of gestation. In the youngest samples (11-16 weeks of age), cytochemistry at the ultrastructural level revealed the presence of rare, mostly circular peroxisomes. From 16 weeks of gestation onwards, an increase was noted in the number of peroxisomes. Two peroxisomal types were distinguished: round to oval forms and elongated and/or tailed organelles. Biochemical assays revealed that total and specific intestinal catalase activities increased gradually between 11 and 20 weeks of gestation. The activity of fatty acylCoA oxidase, the first enzyme of the peroxisomal beta-oxidation system, was detectable as early as 11 weeks of gestation. Thereafter, total and specific activities of the enzyme increased steadily. Activities of other peroxisomal oxidases (D-amino acid oxidase, L-alpha-hydroxyacid oxidase) appeared more slowly in the fetal intestine during the period studied. This investigation establishes the presence and the morphological changes that occur in intestinal peroxisomes during human fetal development as well as the developmental patterns of associated enzymes.
Acyl-CoA Dehydrogenase↗
Genetic abnormalities during transition from Helicobacter-pylori-associated gastritis to low-grade MALToma.
The helicobacter-associated transition from chronic gastritis to MALToma (lymphoma of mucosa-associated lymphoid tissue) may require genetic change in the host. We have studied gastrectomy specimens from twelve cases of primary B-cell gastric lymphoma showing evidence of chronic gastritis and low-grade or high-grade MALToma to look for allele imbalance at microsatellites for six tumour-suppressor genes. We detected allelic imbalance at two of these loci (DCC in three, APC in two). In two DCC cases allele imbalance was seen in the transition from chronic gastritis to low-grade MALToma and in the third between low-grade and high-grade. Allele imbalance between chronic gastritis and low-grade MALToma is not necessarily causal in the transition. Rather, genetic change has occurred in the process of transformation.
Alleles↗
Detection of anti-neutrophil cytoplasmic antibodies by immunoprecipitation.
Immunoprecipitation (IP) of radiolabeled PMN extracts was used as the gold standard for anti-proteinase 3 (PR-3) autoantibody detection to validate immunofluorescence (IF) and alpha granule (alpha) ELISA. A myeloperoxidase (MPO) ELISA was also used in parallel. We studied 48 patients with strictly defined vasculitic syndromes in the initial active phase of their disease. The 3 methods confirmed the high (> 90%) sensitivity and specificity of anti-PR-3 for patients with Wegener's granulomatosis (WG). Similarly, a high (86%) sensitivity of MPO-ELISA was found in microscopic polyarteritis as defined. Using alpha-ELISA, we could not improve the detection rate of anti-PR-3 obtained by IF-cANCA-pattern reading. Moreover, a small proportion (< 15%) of biopsy-proven WG patients had anti-MPO antibodies detected by IF, usually as pANCA but also, even if rarely, as bona fide cANCA (< 5%). Thus, IF would seem to be the most reliable screening method and alpha-ELISA should be used for confirmation. On the other hand, because MPO-ELISA detected twice as many anti-MPO positive sera as did pANCA pattern reading by IF, we suggest that in the clinical context of a vasculitis, MPO-ELISA should also be used as a screening test. Although IP is not designed for routine clinical use, it should be required when reporting the presence of anti-PR-3 in vasculitis-like diseases that are fertile grounds for false positive reactions.
Adult↗
Morphological changes and cellular proliferation in mouse colon during fetal and postnatal development.
To document regional structural and cellular proliferation changes in the developing mouse colon, tissues from fetal, suckling, and weanling mice were analyzed by light microscopy (LM), transmission electron microscopy (TEM), scanning electron microscopy (SEM), [3H]-thymidine incorporation studies, and radioautography. The proximal and distal colon were studied independently at all ages. At 17-18 days of gestation, the mouse proximal colonic mucosa was projected into high and low longitudinal folds disposed in a V-shaped pattern. From birth up to 9 days, the mucosal folds observed by SEM can easily be misinterpreted as being a succession of high and low villus-like structures at LM level. TEM study confirmed the presence of highly specialized absorptive cells in the upper halves of the mucosal folds during this period. No recognizable crypts were noted at birth. Instead, LM and radioautography showed the presence of cell aggregates developing at the base of the epithelium at all levels of the mucosal folds. These cell aggregates evolved into rudimentary crypts giving fully differentiated crypts by day 16 with radiolabeled cells located in the midcrypt portion. As opposed to the proximal segment, a flat mucosa interspersed with well defined short crypts at birth was observed in the distal colon. During the following days, crypts further developed and by 16 days, the radiolabeled epithelial cells were still exclusively located at the base of the crypt. TEM observations illustrated that specialized cells as those found in the proximal segment did not differentiate in this segment.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Immunolocalization of a mesenchymal antigen specific to the gastrointestinal tract.
BACKGROUND: The aim of the present study was to localize, at the fine structural level, a protein found by indirect immunofluorescence to be associated with the mesenchymal tissue 1) closely applied to the intervillus epithelium before the formation of intestinal crypts in the mouse fetus and 2) around intestinal crypts during and after their formation. METHODS: We used a pre-embedding immunolabeling technique for extracellular matrix molecules, and a monoclonal antibody (Mab) directed against antigen MIM-1/130. RESULTS: Immunofluorescence disclosed the presence of antigen 1/130 in the connective tissue closely applied to the epithelium of the gallbladder, pyloric glands, and intestinal and colonic crypts in adult mice. The antigen was absent in all salivary glands, kidney, liver, lung, spleen, and pancreas. At the fine structural level, gold particles in positive organs were associated with the interstitial matrix around collagen fibrils underneath the epithelia; gold particles were completely absent in the basement membranes. In the small intestine, labeling was seen only around crypts from cell position 1 up to the crypt-villus junction; it was totally absent under the villus epithelium. In order to confirm this particular localization in vivo, Mab 1/130 was administered orogastrically to 9-day-old mice: after 3 hours the antibody was found lining the immediate periphery of duodenal crypts as seen by indirect immunofluorescence. In control animals, an anti-mouse laminin Mab of the same subclass as Mab 1/130 was orogastrically fed using the same protocol: basal laminae were labeled under the epithelium of duodenal villi and crypts and also in the lamina propria, with a decreasing gradient from the top of the villi to the bottom of the crypts. CONCLUSION: These observations indicate that the extracellular matrix associated with the epithelium of pyloric glands, of intestinal and colonic crypts, and of gallbladder contains a new antigen whose function remains to be determined. The neonatal mouse hence constitutes a good model to study the role of extracellular matrix components in determining organ differentiation in vivo.
Animals↗
Steady-state pharmacokinetics of methadone in opioid addicts.
Kinetic parameters were investigated in tolerant methadone maintenance patients. The disposition of methadone at steady-state was assessed on 8 occasions-in 5 opioid addicts prescribed wide ranging doses of methadone (10 mg to 60 mg per day)-providing unique pharmacokinetic data. Statistical analysis showed that the kinetics of oral methadone at steady-state were described using a single compartment model. Analysis of the plasma concentration-time curves gave estimates of the variance of methadone clearance and apparent volume of distribution, and indicate that methadone is rapidly absorbed (mean Ka, 1.7 h-1) with a detectable increase in the plasma drug concentration 15 to 30 min after dosing. The elimination of methadone from plasma was found to occur slowly (mean t1/2 26.8 h) beginning soon after the administration of the daily oral prescription. The apparent volume of distribution-assuming the oral bioavailability (f) of methadone to be 0.95--was large (mean 6.7 l.kg-1). The slow clearance of this drug from the body (mean 3.1 ml.min-1.kg-1) confirms that daily dosing at steady-state is adequate to maintain effective plasma concentrations throughout the dosing interval.
Adult↗
Phosphorylated MAP1b, alias MAP5 and MAP1x, is involved in axonal growth and neuronal mitosis.
Microtubule-associated protein 1b, also named MAP5 and MAP1x, is essential for neuronal differentiation. In kitten cerebellum, this protein is partially phosphorylated. During early postnatal development, a phosphorylated form was localized prominently in growing parallel fibres and in mitotic spindles of neuroblasts in the germinal layer, whereas a non-phosphorylated MAP1b form was found in dendrites, perikarya and axons. The MAP1x epitope showed the same immunohistochemical distribution, as seen for phosphorylated MAP1b, while its recognition on immunoblots was independent of phosphorylation. It is concluded that post-translational modifications and conformation of MAP1b influence the immunological detection of MAP1b, and are essential in the neuronal growth processes and mitosis. The antibody against the phosphorylated MAP1b may represent a good marker to identify dividing neurones.
Animals↗
Separate and conjugated in vitro effects of clofibrate and of an organic extract of rat amniotic fluid on microperoxisomes of fetal mouse small intestine.
Separate and conjugated effects of clofibrate and of an organic extract of rat amniotic fluid (RAF) on microperoxisomal response were studied in 15-day-old fetal mouse small intestine in organ culture. At the light-microscopic level, DAB-positive microperoxisomes were not observed in intestinal explants cultured for 48 h with Trowell T8-medium either with (group 1) or without clofibrate (control group) or with the organic extract of RAF alone (group 2). In presence of both clofibrate and the organic extract (group 3), microperoxisomes were readily identified. At the fine structural level, microperoxisomes measured 150-175 nm in diameter in controls and in group 1 and 2. In group 3, numerous microperoxisomes measured up to 0.4 micron in diameter. Total and specific catalase activities exhibited significant decreases when intestinal segments were cultured solely in Trowell T8-medium for 48 h. Addition of clofibrate (1), or of the organic extract of RAF (2), or of both (3) to Trowell T8-medium induced significant increases in total and specific catalase activities: 1.43- and 1.40-fold (1), 2.12- and 2.66-fold (2) and 2.92- and 3.17-fold (3). These results indicate that an organic extract of RAF contains a factor that (a) induces the formation of intestinal microperoxisomes and (b) potentiates the action of clofibrate.
Amniotic Fluid↗
An intestinal secretory protein is found in most glands associated with the gastrointestinal tract: von Ebner's and salivary glands, gallbladder, and pancreas.
We have previously shown that monoclonal antibodies (MAb) prepared against the duodenal mucosa of 4-day-old mice disclosed the presence of two antigens associated with the formation of intestinal crypts. One of these, MIM-1/39, was found in the apical cytoplasm of undifferentiated epithelial crypt cells of the duodenum and colon. We report here the immunolocalization of MIM-1/39 in different glands associated with the gastrointestinal tract, using a polyclonal antibody produced against antigen MIM-1/39. By indirect immunofluorescence on 1-micron thick Lowicryl K4M sections, MIM-1/39 was detected in secretory granules of serous cells in lingual (von Ebner's gland), sublingual, submandibular and parotid glands, and in pancreas; it was also found in epithelial cells of the gallbladder and in the secretory granules of chief cells of gastric glands. Liver, kidney, and Brunner's glands were not immunoreactive. Immunocytochemistry revealed the presence of antigen MIM-1/39 in small secretory granules of the gallbladder, duodenum, colon, and in the large secretory granules in serous cells of lingual and parotid glands, in pancreas, and in gastric chief cells. In Western blotting, the MIM-1/39 MAb revealed two bands (330 and 350 KD) in adult mouse duodenal mucosa, gallbladder and stomach, whereas only one (330 KD) was disclosed in pancreatic juice. However, two bands (330 and 350 KD) were detected in pancreatic juice with the polyclonal antibody. The distribution of MIM-1/39 was different from that reported for IgA, bound and free secretory components, cryptdin, and Tamm-Horsfall protein. Therefore, MIM-1/39 appears to be a unique protein. Its exact role remains to be elucidated.
Animals↗