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J Stein

Publications and source records attributed to J Stein.

At least 235 records · Page 13Linked to original sources
PubMed1995

Patterns of coordinated multi-joint movement.

In multi-joint reaching movements, the motor system may choose any one of an infinite set of possible joint rotations to move the hand between given start and target positions. In order to find out whether reaching movements are represented in Cartesian hand coordinates or in joint coordinates, it is necessary to measure whether hand paths or joint paths have lower variability. We have measured hand paths and rotations of shoulder, elbow and wrist joints simultaneously in five subjects reaching in four orientations in the horizontal plane. As in earlier studies, we found a preference for nearly straight hand paths, despite different patterns of joint rotation for different orientations of movement. However, movements in three of four orientations showed a single principal joint, which rotated essentially without reversals. This may reflect optimisation in the motor system, preferring the simplest pattern of joint control for a desired hand path. We used generalised Procrustes analysis to quantify the variability in shape of repeated paths in hand space and joint space. Results showed that hand paths were less variable than the joint angles used to realise them, due to the kinematic redundancy of the limb, suggesting that hand paths, rather than joint angles, are directly represented by the motor system. Nevertheless, movements with straighter hand paths, on average, and those requiring coordinated activity at both shoulder and elbow joints also showed more variability in the shape of the hand path. Other orientations such as movement across the body use primarily a single joint and are less variable at the cost of a slightly curved path. These results suggest that coordinating multiple joints to produce a straight hand path has a definite computational cost. The motor system may perform a trade-off between the benefits of planning reaching movements as straight hand paths and the computational simplicity of executing them using patterns of joint rotation which simplify multi-joint coordination.

Adult↗
PubMed1995

Isolation and characterization of apical membrane vesicles of the rat distal colon.

In this study a method for the isolation of apical membrane vesicles of the rat distal colon was developed. It is based on the purification of intact membrane caps followed by separation of the vesiculated apical membranes on a discontinous sucrose gradient. Purification of the apical membrane vesicles revealed an 11-fold enrichment of the marker enzyme alkaline phosphatase compared with the homogenate, while marker enzymes of other subcellular structures showed negligible enrichments and recovery of activity. The membrane fluidity (lipid structural order) of the isolated membranes measured from the fluorescence anisotropy by several fluorophores also coincided with the typical structural order of apical membranes of the rat colon. Transport studies with the fluorescent dye acridine orange implied that a diffusion potential independent, amiloride-sensitive Na+ -H+ exchange mechanism is present in the isolated apical membranes. Furthermore, the results suggest that a possible short chain fatty acid (SCFA) absorption by simple passive diffusion of the undissociated form, preceded by intraluminal protonation of the SCFA anion, is not provided by this Na+ -H+ exchange transport in the luminal membrane of the absorptive cell.

Acid Phosphatase↗
PubMed1995

Mercaptopropionate inhibits butyrate uptake in isolated apical membrane vesicles of the rat distal colon.

BACKGROUND/AIMS: Previous observations have shown that mercapto- and bromo- short-chain fatty acids diminish fatty acid use in colonic epithelium. The aim of this study was to investigate whether this effect is attributable to the inhibition of short-chain fatty acid uptake. METHODS: Apical membrane vesicles of rat colonocytes were prepared by a discontinuous sucrose gradient after isolation of membrane caps. [14C]butyrate uptake was measured by rapid filtration technique. RESULTS: Preloading of isolated apical membrane vesicles with bicarbonate or butyrate stimulated [14C]butyrate uptake and resulted in up to fivefold overshoots. Increasing extravesicular butyrate concentrations saturated the bicarbonate-stimulated butyrate uptake with a binding constant of 44.7 +/- 5.9 mmol/L and a maximum velocity of 33.2 +/- 2.7 nmol.mg protein-1.3 s-1. Intravesicular butyrate uptake was inhibited by addition of 20 mmol/L 3-mercaptopropionate (43.0% +/- 5.6%), whereas 2-bromo-propionate (13.9% +/- 4.1%) and 4-bromobutyrate (22.6% +/- 5.3%) did not significantly alter butyrate uptake. Increasing concentrations of 3-mercaptopropionate had a competitive inhibitory effect on butyrate uptake with a binding constant following inhibition of 6.25 +/- 0.87 mmol/L and a maximum velocity of 5.82 +/- 1.01 nmol.mg protein-1.3 s-1. CONCLUSIONS: Butyrate uptake in apical membrane vesicles of rat distal colon is mediated by a low-affinity anion transport system, which can be competitively inhibited by 3-mercaptopropionate but not by 2-bromopropionate and 4-bromobutyrate.

3-Mercaptopropionic Acid↗
PubMed1995

Contrast sensitivity and coherent motion detection measured at photopic luminance levels in dyslexics and controls.

Development dyslexics perform differently from controls on a number of low level visual tasks. We carried out three experiments to explore some of these differences. Dyslexics have been found to have reduced luminance contrast sensitivity at mesopic luminance levels. We failed to replicate this finding at photopic luminance levels. We also compared the (photopic) coherent motion detection thresholds of groups of child and adult dyslexics with those of age matched controls. Dyslexics were significantly less sensitive to motion. The results are discussed in relation to a recent suggestion that developmental dyslexia may be associated with a magnocellular visual deficit.

Adolescent↗
PubMed1995

A comparison of conservative therapy and early selective ligation in the treatment of lymphatic complications following vascular procedures.

BACKGROUND: Lymphatic leakage is a relatively uncommon but serious complication following vascular procedures. A conservative approach consisting of bed rest, leg elevation, prophylactic antibiotics, compressive dressings, and intermittent aspiration is the most commonly used treatment. Because of the long time it takes to cure this condition and the potential for infections, a more aggressive approach consisting of wound exploration and ligation of the leaking lymphatic has been proposed. We review our experience of the past 3 years treating 17 of these complications by using 1 of these 2 approaches. PATIENTS AND METHODS: Seventeen groin complications were seen over a period of 3 years. Ten (59%) patients were treated by selective ligation assisted with isosulfan blue dye injection, and the remaining 7 (41%) were treated conservatively. RESULTS: Mean hospital stay was 2.4 days (range 1 to 4) for the operative group versus 19 days (range 14 to 42) for the conservative group. One complication was seen in the operative group, whereas 4 (57%) patients developed groin infections following conservative therapy. One (10%) patient developed a recurrence following ligation that was treated successfully by reoperation. CONCLUSION: Our experience with the use of surgical ligation of leaking lymphatic assisted by isosulfan blue, when compared with conservative treatment, has led to a decrease in hospital stay, lower complication rates, and fewer recurrences. In our view, this approach represents the best form of treatment for postoperative groin lymphatic complications.

Adult↗
PubMed1995

Fall-related injuries in anticoagulated stroke patients during inpatient rehabilitation.

OBJECTIVE: To compare the frequency and severity of fall-related injuries in anticoagulated patients undergoing rehabilitation after stroke to nonanticoagulated stroke patients undergoing rehabilitation. DESIGN: Retrospective chart review. SETTING: Free-standing rehabilitation hospital. PATIENTS: 264 patients who sustained falls while undergoing intensive inpatient rehabilitation after stroke. MEASUREMENTS: Injuries, categorized as minor (abrasions and bruises) or major (intracranial hemorrhage, fracture, major bleeding). MAIN RESULTS: A total of 400 falls in 264 patients undergoing inpatient stroke rehabilitation were reviewed. One hundred thirty-one falls were sustained by 93 patients receiving anticoagulation, whereas 269 falls were sustained by 175 patients not receiving anticoagulation. In both the anticoagulation group and the control (nonanticoagulated) group, approximately one in five falls resulted in minor injuries (abrasions or bruises). Three fractures occurred, but no major bleeding events or intracranial hemorrhage occurred in either group. CONCLUSIONS: The risk for minor injury secondary to fall is comparable between the two groups, and the risk is low in this setting for hemorrhagic injuries in stroke patients falling while receiving anticoagulation.

Accidental Falls↗
PubMed1995

Contributions of nuclear architecture to transcriptional control.

Three parameters of nuclear structure contribute to transcriptional control. The linear representation of promoter elements provides competency for physiological responsiveness within the contexts of development as well as cycle- and phenotype-dependent regulation. Chromatin structure and nucleosome organization reduce distances between independent regulatory elements providing a basis for integrating components of transcriptional control. The nuclear matrix supports gene expression by imposing physical constraints on chromatin related to three-dimensional genomic organization. In addition, the nuclear matrix facilitates gene localization as well as the concentration and targeting of transcription factors. Several lines of evidence are presented that are consistent with involvement of multiple levels of nuclear architecture in cell growth and tissue-specific gene expression during differentiation. Growth factor and steroid hormone responsive modifications in chromatin structure, nucleosome organization, and the nuclear matrix that influence transcription of the cell cycle-regulated histone gene and the bone tissue-specific osteocalcin gene during progressive expression of the osteoblast phenotype are considered.

Animals↗
PubMed1995

Epidermal growth factor receptor signaling in rat pancreatic acinar cells.

Epidermal growth factor (EGF) regulates pancreatic acinar enzyme secretion. The mechanism of action of EGF in pancreatic acinar cells is not clear. In the present study we investigated the role of heterotrimeric GTP-binding proteins (G proteins) in EGF receptor signal transduction. Pancreatic acini were isolated from rat pancreas by collagenase digestion and permeabilized by digitonin. Activation of phosphatidylinositol 4,5-bisphosphate-specific phospholipase C (PLC) was assessed using a radioreceptor assay specific for inositol 1,4,5-trisphosphate [IP3(1,4,5)]. For measurement of amylase secretion isolated pancreatic acini were incubated with secretagogues for 30 min at 37 degrees C. Amylase released into the medium was assessed by monitoring the hydrolysis rate of p-nitrophenyl-alpha,D-maltohepatoside. The weakly hydrolyzable GTP analogue guanosine 5'-[3-O-thio]triphosphate (GTP gamma S) and guanosine 5'-diphosphate (GDP) were used to activate and inhibit G protein-mediated signal transduction, respectively. EGF (90 nM) stimulated amylase release in isolated pancreatic acini. This effect was enhanced by guanosine 5'-[3-O-thio]triphosphate (0.1 mM), which stimulates G proteins. Guanosine 5'-diphosphate (1 mM), which inhibits the activity of heterotrimeric G proteins, had no effect on basal and EGF-induced amylase release. Lower EGF concentrations (20 nM) inhibited COOH-terminal cholecystokinin octapeptide (CCK8)-induced IP3(1,4,5) production and amylase release in pancreatic acini). However, in the presence of GDP, EGF had no significant effect on CCK8-stimulated amylase release. Furthermore, coincubation of the acini with CCK8, EGF, and GDP revealed that GDP reduces the inhibitory effect of EGF on CCK8-induced IP3(1,4,5) production.(ABSTRACT TRUNCATED AT 250 WORDS)

Amylases↗
PubMed1995

Characterization of putrescine transport across the intestinal epithelium: study using isolated brush border and basolateral membrane vesicles of the enterocyte.

Putrescine transport was investigated in isolated brush border and basolateral membrane vesicles prepared from the rabbit enterocyte. Brush border vesicles were oriented right-side-out and basolateral vesicles inside-out, forming a model representing uptake and extrusion across the intestinal epithelium. Putrescine transport across both membranes was initially rapid, and 66% of the equilibrium uptake was achieved within the first minute. According to osmoplots and measurements at 4 degrees C, 20% of total incorporation presented binding to the membrane. In order to estimate actual uptake into the vesicles, Km was calculated from the differences in putrescine incorporation at 37 degrees C and 4 degrees C, and was 12.7 mumol L-1 for brush border uptake and 38.2 mumol L-1 for basolateral extrusion. Putrescine uptake into brush border and basolateral membrane vesicles was not enhanced in the presence of an Na+ gradient. When Na+ was substituted with an uncharged solute, mannitol, putrescine incorporation was increased, indicating that putrescine uptake is not Na(+)-dependent and that cations might interfere with the carrier. Paraquat and methylglyoxalbis(guanylhydrazone), known to share the polyamine transport system, inhibited putrescine incorporation in both membrane vesicle preparations. Basolateral carrier showed significantly higher sensitivity to cations. We conclude that putrescine uptake across the apical membrane and extrusion across the basolateral membrane of the enterocyte are mediated by two different and independent carriers which differ in their electrical properties.

Animals↗
PubMed1995

Subcellular distribution of small GTP-binding proteins in the intestinal cell line Caco-2.

The present study describes the subcellular distribution of low molecular weight GTP-binding proteins in the human carcinoma cell line Caco-2. Highly enriched subcellular fractions of basolateral and brush border membranes were prepared by differential density centrifugation and divalent cation precipitation. Small molecular weight GTP-binding proteins were identified after SDS-PAGE transfer to nitrocellulose using [alpha 32P]-labelled GTP. Smg-proteins with molecular masses of 28, 27, 25 and 24 kDa were detectable in all fractions. Homogenate and brush border membrane fraction showed specific binding of [alpha 32P] GTP to proteins of a molecular mass of 21 kDa, while in the membrane fractions (apical, basolateral) a high enrichment of 24 kDa smg-proteins was detectable. Western blot analysis identified one of the 21 kDa proteins of the brush border membrane as rhoA. The homogenate of 4, 8, 11 and 14 days old Caco-2 cells showed different [alpha 32P]-GTP binding to 21, 27 and 28 kDa proteins. In conclusion, this study is the first showing the presence and asymmetrical distribution of smg-proteins among the various membrane components in the human carcinoma cell line Caco-2.

Caco-2 Cells↗
PubMed1995

Extracorporeal piezoelectric shock wave lithotripsy as mono and multiple therapy of large renal calculi including staghorn stones in unanaesthetized patients under semi-ambulant conditions.

OBJECTIVE: To examine the effectiveness and complication rate of extracorporeal piezoelectric shock wave lithotripsy (EPL) as monotherapy for the treatment of large renal calculi. PATIENTS AND METHODS: Treatment consisted of semiambulant EPL as monotherapy combined with protective ureteric stenting in 84 patients. Three groups were established according to stone volume (borderline-stone, partial and complete staghorn). An average of 18,230 shock waves was applied in 3.76 sessions to each patient. RESULTS: No major complications were observed but there were minor complications in 33% of patients. Invasive auxiliary methods were necessary in only 12%. After a mean follow-up of 9 months (n = 72), 54% of patients were stone-free and in 22% the fragments passed spontaneously. Thus the success rate was 76%. Analysis of the three groups showed no difference in stone status during follow-up. There was no relation between the outcome of treatment and stone volume. Analysis of the patients who failed to respond to treatment showed that they were treated for longer than the stone-free group, with significantly fewer sessions per week (0.71 vs 1.28 sessions/week). It appears that higher rates of stone removal can be achieved with more frequent treatment sessions at shorter intervals. CONCLUSION: We consider semi-ambulant EPL monotherapy to be a minimally invasive alternative treatment in patients with large renal calculi, including staghorn stones.

Adolescent↗
PubMed1995

Damage to cerebellocortical pathways after closed head injury: a behavioural and magnetic resonance imaging study.

The objective was to investigate the anatomical substrate of ataxia seen after severe head injury. Five patients were recruited from present and former inpatients at Rivermead Rehabilitation Centre. All patients had had a closed head injury and all had cerebellar type ataxia. Four normal controls were also studied. Brain MRI, clinical examination, computer based recording, and analysis of visuomotor tracking were carried out. Focal damage was found in the superior cerebellar peduncle in all five ataxic patients. The patients' tracking movements showed profound tremor, and unusual reliance on visual feedback. Ataxia seen after severe head injury can arise from damage to the superior cerebellar peduncle, which may interfere with the cerebellocortical circuits involved in coordinated movement.

Adult↗
PubMed1995

Transepithelial transport of short chain fatty acids and their metabolism in pig hindgut.

In vitro experiments in Ussing chambers were performed in order to study the transport as well as the intraepithelial metabolism of short chain fatty acids in the caecum, proximal and distal colon. Stripped epithelial tissues were incubated in isotonic buffer solutions. SCFA were only present in the mucosal solutions at a concentration of 60 mmol/l consisting of 60% acetate, 25% propionate and 15% butyrate at the beginning of each flux rate measurement. For osmotic reasons SCFA were completely replaced by gluconate in serosal buffer solutions. The tissues were incubated under short-circuit current conditions for 1 h. In addition, with epithelia from the proximal colon flux rate measurements were also performed after setting the transepithelial potential difference (PD) to 25 mV with the serosa being positive. At the end of each 1h flux period samples were taken from the mucosal and serosal solutions for HPLC analysis of SCFA concentrations. SCFA transport and rate of intraepithelial metabolism were calculated from mucosal uptake and serosal release during the experimental periods. In the presence of 2 cm2 serosal area of the tissues, mucosal SCFA uptake ranged between 53 and 75 mumol with no change of molar SCFA proportions irrespective of hindgut segment. Voltage clamp condition did not influence mucosal SCFA uptake indicating the presence of electroneutral transport mechanisms. Serosal SCFA release ranged between 105 and 126 mumol thus exceeding mucosal loss. In serosal solutions molar butyrate proportions were significantly lower in comparison with mucosal solutions. This was accompanied by slight increases of molar acetate proportions indicating intraepithelial butyrate cleavage.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

The application of a semi-continuous colon simulation technique (Cositec) for studying the effects of clindamycin on microbial hindgut metabolism.

The semi-continuous colon simulation technique was used as an experimental in vitro model to study potential effects of clindamycin application on basic parameters of microbial hindgut metabolism. Hindgut contents from fistulated pigs kept on conventional diets were used as substrates for incubation. Measurements on reproducibility demonstrated the colon simulation technique as a suitable in vitro method to characterize microbial hindgut metabolism and those factors potentially influencing microbial fermentation. Application of clindamycin resulted in disturbances of microbial steady state metabolism and time- and dose-dependent decreases of SCFA production rates with significant reductions of molar butyrate proportions to almost zero. These effects can be related to the onset of functional disturbances of hindgut function under in vivo conditions since butyrate is an essential trophic factor for colonocytes. In addition, clindamycin induced increases in lactate production with a shift towards D-lactate. The relevance of these changes for hindgut function have to be elucidated in further experiments.

Animals↗
PubMed1995

Nonsyndromic cleft lip with or without cleft palate: evidence of linkage to BCL3 in 17 multigenerational families.

Nonsyndromic cleft lip with or without cleft palate (CL/P) is a common craniofacial developmental defect. Recent segregation analyses have suggested that major genes play a role in the etiology of CL/P. Linkage to 22 candidate genes was tested in 11 multigenerational families with CL/P, and 21 of these candidates were excluded. APOC2, 19q13.1, which is linked to the proto-oncogene BCL3, gave suggestive evidence for linkage to CL/P. The study was expanded to include a total of 39 multigenerational CL/P families. Linkage was tested in all families, using an anonymous marker, D19S178, and intragenic markers in BCL3 and APOC2. Linkage was tested under two models, autosomal dominant with reduced penetrance and affecteds only. Homogeneity testing on the two-point data gave evidence of heterogeneity at APOC2 under the affecteds-only model. Both models showed evidence of heterogeneity, with 43% of families linked at zero recombination to BCL3 when marker data from BCL3 and APOC2 were included. A maximum multipoint LOD score of 7.00 at BCL3 was found among the 17 families that had posterior probabilities > = 50% in favor of linkage. The transmission disequilibrium test provided additional evidence for linkage with the 3 allele of BCL3 more often transmitted to affected children. These results suggest that BCL3, or a nearby gene, plays a role in the etiology of CL/P in some families.

B-Cell Lymphoma 3 Protein↗
PubMed1995

Augmentation techniques in laryngotracheal reconstruction.

The treatment of laryngotracheal stenosis remains challenging. Even with the wide variety of current techniques available, optimal reconstruction is not possible for all patients. However, the future of laryngotracheal reconstruction is promising with ongoing development of innovative techniques for repair, as well as the prospect of laryngeal transplantation.

Humans↗
PubMed1994

Visual pontocerebellar projections in the macaque.

The cerebellum plays an important role in the visual guidance of movement. In order to understand the anatomical basis of visuomotor control, we studied the projection of pontine visual cells onto the cerebellar cortex of monkeys. Wheat germ agglutinin horseradish peroxidase was injected into the dorsolateral pons two monkeys. Retrogradely labelled cells were mapped in the cerebral cortex and superior colliculus, and orthogradely labelled fibers in the cerebellar cortex. The largest number of retrogradely labelled cells in the cerebral cortex was in a group of medial extrastriate visual areas. The major cerebellar target of these dorsolateral pontine cells is the dorsal paraflocculus. There is a weaker projection to the uvula, paramedian lobe, and Crus II, and a sparse but definite projection to the ventral paraflocculus. There are virtually no projections to the flocculus. There are sparse ipsilateral pontocerebellar projections to these same regions of cerebellar cortex. In nine monkeys, we made small injections of the tracer into the cerebellar cortex and studied the location of retrogradely filled cells in the pontine nuclei and inferior olive. Injections into the dorsal paraflocculus or rostral folia of the uvula retrogradely labelled large numbers of cells in the dorsolateral region of the contralateral pontine nuclei. Labelled cells were found ipsilaterally, but in reduced numbers. Injections outside of these areas in ventral paraflocculus or paramedian lobule labelled far fewer cells in this region of the pons. We conclude that the principal source of cerebral cortical visual information arises from a medial group of extrastriate visual areas and is relayed through cells in the dorsolateral pontine nuclei. The principal target of pontine visual cells is the dorsal paraflocculus.

Animals↗