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Biomedical subjects

R Dickstein

Publications and source records attributed to R Dickstein.

At least 37 records · Page 2Linked to original sources

Nodules elicited by Rhizobium meliloti heme mutants are arrested at an early stage of development.

Heme-deficient mutants of Rhizobium and Bradyrhizobium have been found to exhibit diverse phenotypes with respect to symbiotic interactions with plant hosts. We observed that R. meliloti hemA mutants elicit nodules that do not contain intracellular bacteria; the nodules contain either no infection threads ("empty" nodule phenotype) or aberrant infection threads that failed to release bacteria (Bar- phenotype). These mutant nodules expressed nodulin genes associated with nodules arrested at an early stage of development, including ENOD2, Nms-30, and four previously undescribed nodulin genes. These nodules also failed to express any of six late nodulin genes tested by hybridization, including leghemoglobin, and twelve tested by in vitro translation product analysis which are not yet correlated with specific cloned genes. We observed that R. meliloti leucine and adenosine auxotrophs induced invaded Fix- nodules that expressed late nodulin genes, suggesting that it is not auxotrophy per se that causes the hemA mutants to elicit Bar- or empty nodules. Because R. meliloti hemA mutants elicit nodules that do not contain intracellular bacteria, it is not possible to decide whether or not the Fix- phenotype of these nodules is a direct consequence of the failure of R. meliloti to supply the heme moiety of hololeghemoglobin. Our results demonstrate the importance of establishing the stage in development at which a mutant nodule is arrested before conclusions are drawn about the role of small metabolite exchange in the symbiosis.

Blotting, Northern↗

Walking reeducation with partial relief of body weight in rehabilitation of patients with locomotor disabilities.

This study was undertaken to investigate the contribution of a weight-relieving system on the gait of patients with severe locomotor disabilities. Temporal parameters of gait and subjective evaluations of the effect of the system were studied in 24 patients and 6 healthy subjects. Partial weight relief was accomplished through a pneumatic system mounted in the ceiling over a conductive walkway which was placed between parallel bars. Subjects were tested in three walking trials: free walking, walking while harnessed to the system but without weight relief, and walking with relief of 20 percent of their body weight. Temporal measurements indicated a positive effect of the system on duration of the stance and swing phases. The percentage of the stance period of the involved lower limb relative to the uninvolved one increased by 148 percent; at the same time, the swing period of the involved limb relative to the sound one decreased to 68 percent of that value in free ambulation. A substantial increase in gait symmetry and velocity were also noted. Subjective information from the patients and observers also pointed to a facilitative effect of the system on the patients' ambulation. Conversely, natural gait velocity of the healthy subjects was impeded by weight relief through the system.

Adult↗

Associative synaptic potentiation and depression: quantification of dissociable modifications in the hippocampal dentate gyrus favors a particular class of synaptic modification equations.

This report further characterizes associative long-term synaptic modification of the ipsilateral and contralateral synapses formed by the bilateral entorhinal cortical (EC) projection to the dentate gyrus (DG). The experimental model is the anesthetized hooded rat. The quantitative results qualify this system as a model for studying the rules of associative synaptic modification formulated in terms of individual synapses. Bilateral DG microelectrodes recorded both ipsilateral and contralateral EC-DG responses before and after brief, high-frequency EC conditioning stimulation. The weak contralateral pathway received high-frequency conditioning before, during, or after similar conditioning of the strong, converging ipsilateral pathway. Statistical analyses revealed two types of significant, dissociated synaptic modifications, which depend on the relationship of the ipsilateral and contralateral afferents. First, contralateral EC-DG responses potentiated or depressed when the converging ipsilateral responses concurrently either potentiated or remained unchanged. Second, contralateral EC-DG responses potentiated, depressed, or showed no change when the collateral ipsilateral responses concurrently either potentiated or remained unchanged. Correlation and contingency table analyses indicated that changes in the contralateral synaptic responses are not well predicted by changes at either neighboring synapses of the converging ipsilateral pathway or at synapses of the collateral ipsilateral pathway. The contingencies of associated pre- and postsynaptic activation determined by the conditioning paradigm, however, accurately predicted the altered synaptic responses of both ipsilateral and contralateral EC-DG pathways. The results imply that associative synaptic modification in the EC-DG system is specific to individual synapses and requires both appropriate presynaptic and postsynaptic activation. Because this system provides suitable controls for nonspecific effects of conditioning stimulation and because modification of neighboring synapses is dissociable, the EC-DG system can be used to study further those rules of activity-dependent associative modification that are formulated in terms of individual synapses. The discussion briefly considers published rules of synaptic modification, pointing out several rules that are not consistent with the experimental observations and one that agrees with the present results.

Animals↗

Responses of ankle musculature of healthy subjects and hemiplegic patients to sinusoidal anterior-posterior movements of the base of support.

The responses of the medical gastrocnemius and tibialis anterior muscles to continuous sinusoidal perturbation of the base of support were studied in two groups of subjects, forty-two volunteers aged 20 to 84 years and 17 hemiplegic patients aged 52 to 81 years. EMGs were recorded while subjects stood on a platform oscillating in the anterior-posterior direction. Movement amplitude was adjusted to the maximum the subject could sustain without assisted support within the limits of the instrument. In healthy subjects, two basic activation modes were indicated: (a) a reciprocal contraction pattern in which activity of the medial gastrocnemius and tibialis anterior muscles was concentrated in the anterior and posterior half of the oscillation, respectively. This pattern prevailed in the younger subjects whose maximal movement amplitude reached the highest limit of the instrument; (b) a less discrete pattern, characterized by tonic contraction and periods of coactivation of the two muscles, was seen in older subjects who had difficulties in maintaining stance on the moving platform. The disruption of the discrete reciprocal response mode in this group of patients was related to decline in function of postural mechanisms with aging and demanded additional stiffening of the ankle join, presumably a manifestation of reduced automatism in favor of closer CNS modulation. The typical response mode in the sound leg of the hemiplegic patients was variable coactivation of the two muscles. In the afflicted leg, the establishment of a motor set was impaired: Low tone was associated with negligible muscular activity, although with more elevated tone, low level uniform cocontraction was evident.

Journal Article↗

Electromyographic responses of distal ankle musculature of standing hemiplegic patients to continuous anterior-posterior perturbations during imposed weight transfer over the affected leg.

This study was undertaken to evaluate the influence of weight shift over the affected leg of standing hemiplegic patients on the electromyographic responses of the medial gastrocnemius and tibialis anterior muscles during continuous anterior-posterior movements of the base of support. Recordings were taken from 10 hemiplegic subjects and from 9 healthy subjects of comparable age. Each subject was first tested standing with both feet on a level surface and then with either leg (in healthy subjects) or the unaffected leg (in hemiplegic subjects) raised on a step. The second testing position caused unloading of the elevated leg and weight shift, that is, loading of the other leg. The measured variables were modulation of muscular activity, determined by a modulation index formulated for that purpose, and the relative amount of integrated electromyographic activity in each muscle. Changes in both variables in the uneven stance position as compared with even stance, occurred primarily in the unaffected (unloaded) leg in the hemiplegic subjects. These changes were comparable to changes in the unloaded leg of the healthy subjects. Thus, imposed loading on the affected leg of the hemiplegic subjects did not significantly improve either the reduced modulation or the relatively low IEMG activity of the investigated muscles. Further studies are required to evaluate the contribution of weight shift to recovery of postural responses in the affected leg of hemiplegic patients.

Ankle Joint↗

Postural responses of normal geriatric and hemiplegic patients to a continuing perturbation.

The electromyographic (EMG) activity of the gastrocnemius and tibialis anterior muscles was recorded from normal geriatric subjects and from hemiplegic patients subjected to a continuous back-and-forth movement of the platform on which they stood. The platform oscillated at a fixed frequency of 0.5 Hz. Movement amplitude was the largest each patient could withstand without support of the hands. Standing on the moving platform continued for 5 min. EMG recordings continued for 60 s, commencing 2 min after movement onset. Analysis of the EMG, in normal subjects revealed a typical pattern of reciprocal activity in the tibialis anterior and gastrocnemius, in synchrony with the back-and-forth movements of the platform. The cyclic activation of each muscle started before movement of the platform could cause its stretch. The normal movement-induced pattern of leg muscle activation was greatly disturbed or totally absent in hemiplegic patients. In such patients, various patterns of tonic activation of one or both muscles were observed in the sound as well as the afflicted leg. Occasional periodic activation of one muscle or the other was observed. However, such activation was not well synchronized with movement of the platform and did not last long. Based on the above observations, we concluded that the ability to adapt to a rhythmic platform movement by production of anticipatory phasic muscular contractions is severely disrupted in hemiplegics.

Aged↗

The expression of the Escherichia coli uvrA gene in human cells.

Cells cultured from xeroderma pigmentosum (XP) patients are defective in excision repair of damaged DNA specifically at the incision step. In Escherichia coli this step is mediated by the UvrA, UvrB and UvrC gene products. Our goal is to express each of these genes in XP cells, singly or in combination, and to determine the most suitable conditions for generating faithful E. coli Uvr protein copies in functional concentrations and properly localized for the eventual repair of damaged chromosomal DNA or DNA which is introduced exogenously. The E. coli gpt gene in pSV2gpt is used as a selection marker for uvr gene transfection into XP cells. The uvr genes were cloned into composite pBR322, SV40 and gpt vectors in which each E. coli gene is flanked by individual SV40 regulatory elements. SV40-transformed XP-A cells were transfected with pSV2uvrASV2gpt, gpt+ colonies were selected, and cell lines established. Several lines were examined in detail. Cell lines 714 and 1511 contain uvrA together with flanking SV40 regulatory elements integrated intact in genomic DNA and express UvrA protein as well as a 95,000-dalton UvrA-related protein. The expression of uvrA was found to be 50-100-fold lower than the expression of gpt. Attempts were made to assay the mammalian UvrA protein for functionality, but endogenous activities interfered with assays for each of the UvrA protein's three activities. The peptide maps derived from partial proteolysis of the "mammalian" UvrA protein are identical to the E. coli UvrA protein. The sub-cellular location of UvrA protein in uvrA+ XP cells was investigated by fractionation of cell extracts in which an indirect immunofluorescence method revealed its location as being largely extra-nuclear. Two uvrA+ cell lines were examined for their UV-resistant phenotype and not unexpectedly were found not to be reverted to a state of repair proficiency.

Bacterial Proteins↗

Developmental regulation of nodule-specific genes in alfalfa root nodules.

We have cloned alfalfa nodule-specific cDNAs that code for leghemoglobin (Lb), glutamine synthetase (GS), and three unidentified nodulins. Hybrid-select translation of nodule RNA followed by 2-D gel electrophoresis showed that the Lb-specific cDNA corresponded to at least four Lb species of 12 kDa. One of the unidentified cDNA clones (N-32/34) corresponded to at least five polypeptides of 32-34 kDa; a second unidentified cDNA clone (N-14) corresponded to an individual polypeptide of 14 kDa. The in vitro translation product(s) of the RNA hybrid selected by the third unidentified cDNA clone (N-22) formed a single band at 22 kDa on a one-dimensional gel. Northern and dot blot analyses of RNA isolated from wild-type nodules and from defective nodules elicited by a variety of Rhizobium meliloti mutants showed that 1) RNAs corresponding to the Lb, nodule-specific GS, and three unidentified nodulins were coordinately expressed during the course of nodule development, and 2) all five nodulins were expressed in Fix- nodules that contained infection threads and bacteroids but were not expressed in nodules that lacked infection threads and intracellular rhizobia.

Base Sequence↗

Expression of nodule-specific genes in alfalfa root nodules blocked at an early stage of development.

To help dissect the molecular basis of the Rhizobium-legume symbiosis, we used in vitro translation and Northern blot analysis of nodule RNA to examine alfalfa-specific genes (nodulins) expressed in two types of developmentally defective root nodules elicited by Rhizobium meliloti. Fix- nodules were elicited by R. meliloti nif mutants; these nodules were invaded by rhizobia and contained differentiated bacteroids. 'Empty' nodules were elicited by R. meliloti exo and ndv mutants and by Agrobacterium tumefaciens strains carrying the R. meliloti nod genes; these nodules contained a nodule meristem but lacked infection threads, intracellular bacteria, and bacteroids. Fix- nodules contained a spectrum of nodulins similar to wild-type nodules. In contrast, only two nodulins, Nms-30 and a nodulin homologous to ENOD2 of soybean, were detected in empty nodules. Although R. meliloti ndv and exo mutants elicited nodules with the same defective phenotype, ndv and exo mutants (except for exoC mutants) had distinct biochemical phenotypes. R. meliloti ndvA and ndvB mutants were deficient in cyclic glucan production but not the acidic exopolysaccharide; the converse was true for exoA, exoB, and exoF mutants. exoC mutants were defective in both exopolysaccharide and cyclic glucan biosynthesis. Our results support the model that the R. meliloti nod genes produce a signal that results in nodule meristem induction. Both the exopolysaccharide and cyclic glucan, however, appear to act at the next step in the developmental process and are involved in the production of a signal (or structure) that allows infection thread formation and invasion of the nodule.

Amino Acid Sequence↗

The contribution of vision and of sidedness to responses of the ankle musculature to continuous movement of the base of support.

Eight healthy women were subjected to continuous sinusoidal movements of the base of the platform on which they stood. Each subject was tested once in the anterior-posterior (AP) and once in the lateral movement direction. In the first 30 s of each test, subjects' eyes were open while during the following 30 s their eyes were closed. Bilateral EMG recordings from the Medical Gastrocnemius (MG) and the Tibialis Anterior (TA) muscles were continuously taken from the moment subjects became used to the imposed movement. Results revealed that during AP movements the MG and TA muscles were reciprocally activated and deactivated, thereby continuously stabilizing the ankle joint in advance of the imposed anterior or posterior perturbation. Similarly, during lateral movements each MG muscle was activated in the homologous side of the movement trajectory. These basic postural sets were neither affected by elimination of vision nor by sidedness. However, absence of vision caused decrease of the ratio between the IEMG of the MG muscle to that of the TA muscle during AP movements. This decrease resulted from decrease in the activity of the MG muscles and/or from increased activity of the TA muscles while vision was eliminated. The latter phenomenon occurred to a greater extent in the right leg.

Adult↗

Operated versus non-operated hip fractures in a geriatric rehabilitation hospital.

A comparative study between 53 non-operated and 170 operated hip fractures was conducted in a geriatric rehabilitation hospital. The non-operated fractures were mainly of the trochanteric type. Time interval between the fracture and admission date to rehabilitation was shorter than 1 month for both groups. At the end of the rehabilitation treatment, 39.6% of the non-operated cases and 64.1% of the operated regained full walking independence. Fifteen per cent of the non-operated patients and 12.3% of the operated were able to walk with assistance, and 35% of non-operated cases versus 17.6% of operated cases remained unable to walk. Mortality rate was greater among the non-operated patients. Despite significant between-group difference in ambulatory capacity in favour of the operated group, the results support the view that a substantial percentage of non-operated patients can regain ambulation. Extraneous factors to the fracture itself such as mental status and motivation probably play a role in successful rehabilitation of the latter.

Activities of Daily Living↗

Influence of sequential pneumatic compression on postoperative venous function.

Sequential external pneumatic compression (SEPC) has been reported to decrease the incidence of acute deep venous thrombosis in postoperative patients by a direct mechanical action on the lower extremity veins and/or by inducing alterations in systemic fibrinolysis. To evaluate the effect of SEPC on venous function in the postoperative patient, pre- and postoperative venous capacitance (VC) and outflow (VO) were measured in a series of general surgical patients. In phase I, 17 limbs were evaluated in patients who had been fully ambulatory preoperatively and at complete bed rest postoperatively. VC decreased from 3.19 +/- 0.43 cc/100 cc of tissue (mean +/- standard error of the mean) preoperatively to 2.08 +/- 0.34 cc/100 cc of tissue postoperatively (p less than 0.05) and VO decreased from 87.2 +/- 10.6 cc/100 cc of tissue/min preoperatively to 58.1 +/- 8.7 cc/100 cc of tissue/min postoperatively (p less than 0.025). In phase II SEPC was begun preoperatively and continued for 24 hours postoperatively on one limb of 20 patients. SEPC prevented the decrease in VC and VO both in the pumped leg (VC-2.65 +/- 0.26 cc/100 cc of tissue preop, 2.40 +/- 0.18 cc/100 cc of tissue postop, p greater than 0.2; VO-72.3 +/- 5.9 cc/100 cc of tissue/min preop, 66.2 +/- 5.3 cc/100 cc of tissue/min postop, p greater than 0.2) and in the unpumped limb (VC-2.85 +/- 0.18 cc/100 cc of tissue preop, 2.41 +/- 0.24 cc/100 cc of tissue postop, p greater than 0.05; VO-66.1 +/- 5.2 cc/100 cc of tissue/min preop, 66.7 +/- 6.7 cc/100 cc of tissue/min postop, p greater than 0.5).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Stroke rehabilitation. Three exercise therapy approaches.

The purpose of this study was to compare the therapeutic efficacy of three exercise therapy approaches. Three groups of adult stroke patients (N = 131) participated in the study. The first group received conventional treatment that consisted of traditional exercises and functional activities. The treatment of the second group was based on proprioceptive neuromuscular facilitation techniques. The third group was treated using the Bobath approach. The improvement of each patient was evaluated after six weeks of treatment in terms of functional gains in activities of daily living as measured using the Barthel index, changes in the muscle tone of the involved limbs as measured using a five-point ordinal scale, changes in the isolated motor control of the ankle and wrist as measured by tests of muscle strength and range of motion, and changes in the patients' ambulatory status as measured using a nominal scale of four categories. The therapeutic effects of exercise according to each of the three approaches were compared using descriptive and nonparametric statistical methods. No substantial advantage could be attributed to any one of the three therapeutic approaches.

Activities of Daily Living↗

Effects of lidocaine on the function of immunocompetent cells. I. In vitro exposure of mouse spleen lymphocytes and peritoneal macrophages.

In vitro exposure of mouse lymphocytes and macrophages for 24 h to noncytotoxic doses of lidocaine (10(-4) to 10(-6)M) resulted in inhibition of random macrophage motility and in an interference with the production of macrophage migration inhibitory factor or with its interaction with the cell surface. The effects of lidocaine, membrane-stabilizing local anesthetic, were related to its concentration in the medium and to its ability to interact with the cell surface and cause changes in the ionic configuration of the plasma membrane. The drug conferred permanent changes on the surface of lymphocytes at all concentrations tested, but changes in the surface of macrophages induced by 10(-5) and 10(-6)M lidocaine were reversible. The presence of noncytotoxic doses of lidocaine in the cellular environment resulted in significant changes in cellular functions that appeared to be related to the ability of the drug to interact with cell membranes in a manner determined by the specific properties of the cell.

Animals↗

Effect of lidocaine on the function of immunocompetent cells. II. Chronic in vivo exposure and its effects on mouse lymphocyte activation and expression of immunity.

In vivo exposure of mice to lidocaine (0.25 mg/10 g body weight 4 times a day for 7 days) resulted in impairment of immunocompetent cell function. Spleen lymphocytes removed from animals immediately and 3 days after lidocaine exposure showed changes in their surface charge properties, inhibition of blastogenesis in response to concanavalin A and lipopolysaccharide, and inhibition of antigen-stimulated activation as measured by the mixed lymphocyte reaction. Lymphocytes from animals sensitized to keyhole limpet hemocyanin showed a significantly lower capacity to produce macrophage migration inhibitory factor 8 days after termination of exposure to lidocaine. Animals exposed to the drug were unable to accumulate an adequate number of immunocompetent cells at the site of challenge with a foreign substance (i.e. dextran), and the ability of the animals to destroy tumor cells nonspecifically and specifically was also impaired. The results indicated that chronic exposure to lidocaine resulted in impairment of lymphocyte function, even in the subsequent absence of the drug, and in significant changes in the expression of the immune response.

Animals↗