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Theoretical and practical considerations in the restoration of function after stroke.

Recovery of function after stroke appears to include elements of both restoration and compensation. The brain is highly plastic, which allows reorganization after damage. Stroke produces permanent damage to the brain, so recovery must be based on activity in surviving cells that are either adjacent, contralateral, or in a different region. Furthermore, representation of a particular function in the brain is usually not limited to a single brain region. Multiple representation provides the opportunity for brain reorganization; functions are assumed by surviving brain structures. Compensation can be the initial response in the recovery phase and may persist through later phases because of the new habits formed (as the restraint therapy studies of Taub and others would suggest), because the damage to the brain is extensive and hinders restoration, because of secondary pathology, such as tendon shortening and muscle wasting, that does not allow brain reorganization to be translated into functional recovery, or because of inadequate (especially late) rehabilitation.

Journal Article↗

Blind phase shift estimation in phase-shifting interferometry.

A blind phase shift estimation algorithm that allows simultaneous calculation of phases and phase shifts from three or more interferograms is presented. In phase-shifting interferometry, the phase shift errors introduce specific correlations between the calculated background intensity distribution and the fringe component. These correlations can be measured with a cross-power spectrum. By minimization of an objective function based on this cross-power spectrum, the actual phase shifts are estimated and used for phase recovery. The validity of this algorithm is verified by both the numerical simulation and the experiment results.

Algorithms↗

Suppression of hematopoiesis by activated T-cells in infectious mononucleosis associated with pancytopenia.

Two patients with primary Epstein-Barr virus (EBV) infection followed by pancytopenia were studied. They showed increased numbers of DR-positive, activated T-cells and serological evidence of persistent EBV infection over a 12 and 18 week period. Bone marrow granulocyte-macrophage colony formation (CFU-GM) was investigated by limiting dilution assay (LDA) and methylcellulose assay. CFU-GM of bone marrow mononuclear cells (BMMNC) was markedly suppressed in both patients during the pancytopenic phase. Removal of bone marrow T-cells by E-rosetting resulted in a significant increase of CFU-GM to normal levels in BMMNC of both patients, while no significant increase was observed in the BMMNC of normal subjects. CFU-GM in BMMNC from Patient 1 in the recovery phase was normal when DR-positive T-cells were within normal levels, irrespective of the presence or absence of T-cells. These results suggest that pancytopenia due to infectious mononucleosis in these patients was due to bone marrow suppression by activated T-cells. In vitro studies with Con A activated T-cells and their culture medium showed that suppression of CFU-GM by T-cells was mediated by a lymphokine.

Adult↗

[Overexpression of bcl-2 suppresses apoptotic cell death of the human leukemic cell line TF-1].

We analyzed the effect of overexpression of bcl-2 gene on cell cycle progression, using the growth factor dependent cell line, TF-1, derived from an erythroleukemia patient. TF-1 (bcl-2) cells, which were transfected with bcl-2 cDNA by the retrovirus vector system, survived and arrested in the G0-1 phase on GM-CSF removal. Centrifugal elutriation studies showed that G0-1-arrested subfraction of TF-1 (bcl-2) reentered the cell cycle with time delay upon GM-CSF re-addition, when compared with TF-1 (mock). A similar delay in cell cycle progression was observed during the recovery phase after 24h-exposure to staurosporine, a protein kinase C(PKC) inhibitor. These results imply functional involvement of bcl-2, both in the GM-CSF and the PKC signal transduction pathway and in G0-1 progression.

Apoptosis↗

Dynamics of cardiac period responses after prolonged vagal stimulation in the dog.

In 12 dogs anesthetised with alpha-chloralose and urethane, and beta-adrenergic blocked with propranolol, the cervical vagi were stimulated for 60 seconds with supramaximal constant current pulses at frequencies between 2.0 and 10 Hz. The time course of the recovery of the cardiac period response, after cessation of vagal stimulation, was analyzed using nonlinear curve fitting techniques. It was found that the recovery phase could be reliably fitted with a function consisting of the sum of up to three exponential terms. The first term has a moderate rate constant of 0.2260 +/- 0.0112 S-1 (SE) and is independent of vagal stimulus frequency and the preceding bradycardia. We propose that this term is associated with a recovery from the bradycardia with a rate constant indicative of the reduction of acetylcholine at the pacemaker caused by hydrolysis and washout. The second term has a small rate constant of 0.0499 +/- 0.0014 s-1 (SE) and a negative gain. This term describes the time course of the post vagal tachycardia observed at cessation of stimulation. It is also independent of stimulus frequency and the preceding bradycardia. The third term has a large and variable rate constant (range: 0.247-8.01 s-1) and becomes increasingly dominant when the preceding bradycardia is large. We propose that this third component arises from a rapid return of the pacemaker focus to the dominant location prior to vagal stimulation. The mathematical characterisation of this component is important to permit the accurate derivation of the time courses of the remaining two components. Curvilinear relationships exist between the gain parameters for each of the exponential terms and the preceding bradycardia.

Acetylcholine↗

Recovery of electromyograph median frequency after lumbar muscle fatigue analysed using an exponential time dependence model.

The recovery of the median frequency of the power spectrum of the electromyogram (EMG) after fatigue has been studied to obtain reference data for healthy subjects (n = 55). In a seated position, the subjects performed a 45 s isometric back muscle contraction at 80% of maximal voluntary contraction, followed by 5 s contractions after 1, 2, 3, and 5 min in the recovery phase. In an additional reliability study (n = 11), this was performed six times. Surface EMG was recorded on four sites, namely, bilaterally from the lumbar muscles at the level of the first (L1) and fifth (L5) vertebrae. By non-linear regression, an exponential time dependence model was used to analyse the recovery of median frequency, giving recovery half-time as a resulting measure. Agreement with exponential time dependence was very good (coefficient of determination r(2) = 0.98) in the analysis of mean data (n = 55), with recovery half-times in the range 32-39 s on the four recording sites. Analysis of individual recordings, for which r(2) values in general were lower, revealed further details. Median values of the half-times in general agreed well with the half-times obtained from the analysis of mean data. Recovery half-time and median frequency slope during contraction were not correlated; this is in agreement with what may be expected from an exponential time dependence. Non-significant negative slopes occurred on apparently randomly selected sites, possibly indicating varying muscle coordination in the seated test method. The reliability of the half-time was not sufficient to allow for follow-up measurements on individuals, due to the fluctuations of the recovery data in recordings from individuals.

Adult↗

Changes in oxygen consumption induced by t-butyl hydroperoxide in perfused rat liver. Effect of free-radical scavengers.

The addition of t-butyl hydroperoxide to perfused rat liver elicited a biphasic effect on hepatic respiration. A rapid fall in liver oxygen consumption was initially observed, followed by a recovery phase leading to respiratory rates higher than the initial steady-state values of oxygen uptake. This overshoot in hepatic oxygen uptake was abolished by free-radical scavengers such as (+)-cyanidanol-3 or butylated hydroxyanisole at concentrations that did not alter mitochondrial respiration. (+)-Cyanidanol-3 was also able to facilitate the recovery of respiration, the diminution in the calculated rate of hydroperoxide utilization and the decrease in liver GSH content produced by two consecutive pulses of t-butyl hydroperoxide. It is suggested that the t-butyl hydroperoxide-induced overshoot in liver respiration is related to increased utilization of oxygen for lipid peroxidation as a consequence of free radicals produced in the scission of the hydroperoxide by cellular haemoproteins.

Animals↗

Changes of neurotransmitter systems in chronic relapsing experimental allergic encephalomyelitis in rat brain and spinal cord.

Catecholamine and indoleamine neurotransmitters, together with some of their precursors and metabolites, were determined using HPLC in three brain and two spinal cord regions of Lewis rats with chronic relapsing allergic encephalomyelitis and of control rats injected with complete Freund's adjuvant. Three attacks and two recovery phases were investigated. Changes are found mainly in the spinal cord. In the lumbosacral region both 5-hydroxytryptamine and noradrenaline are reduced during the entire course of the disease, whereas in the craniothoracal region 5-hydroxytryptamine is unchanged and only noradrenaline is reduced during the attacks, returning to normal during the first recovery. The precursors tyrosine and tryptophan are greatly elevated during the first two attacks in both regions. The 5-hydroxytryptamine turnover marker 5-hydroxyindoleacetic acid is increased in the first attack in both regions, then it decreases in the later stages, indicating destruction of nerve fibers. On the fourth and seventh days after inoculation values are generally not significantly different from controls in all regions. The possible correlation of neurochemical results with neurological signs is discussed.

Animals↗

Cellular repopulation and recovery of the phytogemagglutinine (PHA) responding cell pool in the thymus of sublethally irradiated mice.

Cellular repopulation and recovery of PHA reactivity was investigated in the thymus of mice exposed to 400 R either on the whole body or with one leg protected. In the whole body irradiated cases both the cellular repopulation and the restoration of PHA reactivity in the thymus showed a cyclic pattern: an initial depression and a subsequent first recovery being followed by a secondary cellular depletion and decrease of reactivity before another recovery phase started. The phase of the secondary decrease lasted fo a similar period for both the cell number and reactivity, but was shifted in time and the reduction in reactivity began some 12 days later than that in the cell number. In the leg-shielded animals, the cellular repopulation progressed without cyclic changes, but the recovery of PHA reactivity maintained a cyclic pattern. However, due to a smaller secondary decrease, it was less pronounced than in the whole body irradiated cases. During the aging of mice from 50 to 90 day old, the cell number in the involuting thymus decreased to half of the original. The decrease in the cell population was associated with an about four-fold increase of PHA reactivity. The results were discussed in regard to the origin of the immunoreactive thymic cells. Arguments were presented in favour of the hypothesis that both the reactive and nonreactive cells originate from precursors in common, but require different lengths of time for maturation.

Aging↗

Oligozoospermia induced by exogenous testosterone is associated with normal functioning residual spermatozoa.

OBJECTIVE: To determine the functional capacity of residual spermatozoa in semen samples from normal men with T enanthate-induced oligozoospermia. DESIGN: Prospective clinical study. SETTING: Academic research center. PATIENT(S): Twelve healthy men were studied while participating in a multicenter T enanthate contraceptive efficacy study. Data were analyzed from only eight subjects, whose sperm concentrations were between 1.3 and 10 x 10(6)/mL at the suppression phase. INTERVENTION(S): Testosterone enanthate (200 mg) was administered IM weekly during the suppression and treatment (efficacy) phases (total 15 months). MAIN OUTCOME MEASURE(S): Sperm function tests (stimulated acrosome reaction, sperm hyperactivation [HA], and zona-free hamster oocyte penetration tests) were performed during the pretreatment, suppression (usually after 6 to 10 weeks of treatment, when sperm concentration was anticipated to decrease to < 10 x 10(6)/mL), and recovery phases. Studies were not done during the contraceptive efficacy phase because only one of the subjects was not azoospermic. RESULT(S): Mean sperm concentration was reduced but sperm motility, motility characteristics, and morphology were not affected by T enanthate treatment. The residual spermatozoa in the ejaculate could acrosome react, exhibited normal HA, and maintained the capacity to penetrate and fuse with the oocyte. CONCLUSION(S): Suppression of spermatogenesis to moderate oligozoospermia (< 10 x 10(6)/mL) with exogenous T enanthate administration was not associated with impaired sperm function of the residual spermatozoa. The study did not exclude the possibility that disorders of sperm function might occur when spermatogenesis is suppressed further to very severe oligozoospermia (< 1 x 10(6)/mL), commonly observed in hormonal male contraceptive clinical trials.

Adult↗

Systemic neutrophil response resulting from dental plaque accumulation.

BACKGROUND: There is considerable current interest in putative relationships between oral and systemic diseases. Since the host response to oral bacteria may be the critical link in this association, our hypothesis was that dental plaque accumulation in healthy subjects would elicit a systemic inflammatory response. METHODS: Twenty-three healthy subjects, aged 18 to 25, participated in a 4-phase study. An initial hygiene phase was followed by a 21-day experimental phase (the so-called experimental gingivitis model) in which subjects refrained from all oral hygiene practices, thus permitting the accumulation of bacterial plaque. At days 0, 7, and 21 total and differential peripheral white blood cell (wbc) counts, together with full mouth plaque and gingivitis scores, were recorded. Following a 28-day recovery phase, in which normal oral hygiene practices were resumed, subjects entered the final 21-day control phase which mirrored the experimental phase but with subjects maintaining normal oral hygiene practices. RESULTS: The experimental model performed as anticipated with a correlation between plaque and gingivitis scores of 0.95, also reflecting subject compliance. Total wbc and neutrophil counts increased during the experimental phase. Furthermore, comparison of neutrophil counts between the experimental and control phases demonstrated a significantly higher cell count for the experimental phase on both days 7 and 21 (P= 0.0301 and 0.009, respectively). For total wbc, this was significant on day 21 (P= 0.0262). CONCLUSION: The results of this study support the hypothesis that the accumulation of dental plaque can result in a measurable systemic inflammatory response, providing further in vivo data to support a mechanistic relationship between oral and systemic pathology.

Adolescent↗

[Japanese encephalitis presenting with left hemiplegia and thalamic neglect--a case report].

This report concerns a 51-year-old right-handed man with Japanese encephalitis, showing left hemiplegia and left hemispatial neglect. On admission, he had a slight fever, mild consciousness disturbance, left hemiplegia, and left hemispatial neglect but no neck stiffness, headache nor nausea. He was treated on the basis of cerebral infarction, but his fever and consciousness disturbance worsened. We found pleocytosis (145/mm3) in the cerebrospinal fluid (CSF) and right thalamic edema on a brain CT scan obtained 4 days later. He was finally diagnosed as having Japanese encephalitis on the basis of an increase in anti-viral antibodies observed in paired CSF and serum samples. In the exacerbation phase, 123I-IMP single photon emission CT (SPECT) demonstrated a marked decrease in cerebral perfusion in the right hemisphere, while a brain MRI revealed irregular lesions localized the right thalamus (mainly posterior and medial parts), showing low intensity on T1-weighted and high intensity on T2-weighted images. In the recovery phase, asymmetrical perfusion was no longer observed on SPECT and the symptoms including the left hemispatial neglect had improved. These findings suggest that the left hemispatial neglect in this patient might been caused by the right thalamic lesion resulting in damage to the activating system of the right hemisphere. This case thus shows that acute onset of hemispatial neglect could be caused by cerebral encephalitis.

Cerebral Infarction↗

The role of hind limb flexor muscles during swimming in the toad, Bufo marinus.

Most work examining muscle function during anuran locomotion has focused largely on the roles of major hind limb extensors during jumping and swimming. Nevertheless, the recovery phase of anuran locomotion likely plays a critical role in locomotor performance, especially in the aquatic environment, where flexing limbs can increase drag on the swimming animal. In this study, I use kinematic and electromyographic analyses to explore the roles of four anatomical flexor muscles in the hind limb of Bufo marinus during swimming: m. iliacus externus, a hip flexor; mm. iliofibularis and semitendinosus, knee flexors; and m. tibialis anticus longus, an ankle flexor. Two general questions are addressed: (1) What role, if any, do these flexors play during limb extension? and (2) How do limb flexors control limb flexion? Musculus iliacus externus exhibits a large burst of EMG activity early in limb extension and shows low levels of activity during recovery. Both m. iliofibularis and m. semitendinosus are biphasically active, with relatively short but intense bursts during limb extension followed by longer and typically weaker secondary bursts during recovery. Musculus tibialis anticus longus becomes active mid way through recovery and remains active through the start of extension in the next stroke. In conclusion, flexors at all three joints exhibit some activity during limb extension, indicating that they play a role in mediating limb movements during propulsion. Further, recovery is controlled by a complex pattern of flexor activation timing, but muscle intensities are generally lower, suggesting relatively low force requirements during this phase of swimming.

Animals↗

Postichemic renal failure: accelerated recovery with adenosine triphosphate-magnesium chloride infusion.

Since previous studies have shown a protective effect of the administration of adenosine triphosphate-magnesium chloride (ATP-MgCl2) in shock, the present study was undertaken to determine the effect of the infusion of ATP-MgCl2 after 30 minutes of renal artery occlusion. In animals who received no infusion or only MgCl2, the combination of reduced glomerular filtration rate (GFR), marked diuresis, and reperfusion of the outer cortex suggested that these animals were in the early recovery phase of acute renal failure. In the animals who received ATP-MgCl2, there was improved GRF, no diuresis, and a normal pattern of cortical blood flow distribution. These findings would suggest that the infusion of ATP-MgCl2 appears to have either ameliorated the effect of renal ischemia, or to have accelerated the recovery process. While the precise mechanism of action of ATP-MgCl2 remains unknown, these observations may have important implications for future use in organ preservation and the management of acute renal failure.

Acute Kidney Injury↗

NIRS monitoring of pilots subjected to +Gz acceleration and G-induced loss of consciousness (G-LOC).

With the increasing maneuverability of modern aircraft, there is an increased frequency of pilots losing consciousness due to high +Gz acceleration. This phenomena is defined as "G-induced loss of consciousness" (G-LOC). We used an NIRS system of our design to monitor cerebral oxygenation changes of pilots subjected to high +Gz acceleration and G-LOC. During the +Gz pulse, delta HbO2, and delta TotalHb decreased, with lesser changes of delta Hb. The maximum decrease of delta HbO2 and delta TotalHb usually occurred at the onset of G-LOC. After G-LOC, delta HbO2 and delta TotalHb increased rapidly for the first few seconds, beginning the reactive hyperemic recovery phase. delta HbO2 and delta TotalHb peaked, and then began to decrease towards baseline. The subjects were unconscious for 3-10 seconds after the onset of G-LOC. Upon returning to consciousness, the subjects were disoriented for another 4-11 seconds. NIRS provides an additional means of studying physiological mechanisms leading to and recovery from G-LOC.

Acceleration↗

Factors determining changes in lower limb energy during swing in treadmill running.

This investigation determined the manner in which the lower limb is supplied with mechanical energy in the recovery phase of treadmill sprinting. This was done by following energy input to each limb segment through joint force power and muscle moment power. Joint force power and concentric muscle moment power at the hip are responsible for changes in limb energy although eccentric knee muscle moment power continually reduces total limb energy. In early recovery energy is transmitted distally to raise all segmental energies. In late recovery energy lost from shank and foot is transmitted proximally to the hip without loss in thigh energy. Interlimb exchanges of energy indicate that energy lost in late recovery is transmitted across the pelvis to provide a gain in energy in the opposite limb in early recovery. Much of the loss in limb energy appears to result from the presence of two joint muscles.

Biomechanical Phenomena↗

Oral levo-norgestrel - testosterone effects on spermatogenesis, hormone levels, coagulation factors and lipoproteins in normal men.

Four healthy men volunteered to be treated for eight to nine months with daily oral levo-norgestrel (250 micrograms) and oral testosterone (200-600 mg) as a possible contraceptive. This was followed by a recovery phase of 5-10 months. The oral steroid combination significantly decreased sperm count in 3 of 4 subjects, and significantly increased abnormal spermatozoa, serum LH was decreased during treatment but serum FSH remained constant, except for one volunteer. Serum testosterone was decreased except for 2 daily peaks associated with the oral testosterone. During the recovery period, sperm counts and morphology, serum testosterone and serum LH returned to normal, whereas serum FSH levels were increased. Platelet aggregability induced by ADP, increased in 3 volunteers during treatment as did fibrinolytic activity and fibrinolytic capacity (2 of 3 subjects). There was a reduction in the hepatic triglyceride lipase activity but no change was seen in serum triglycerides, serum cholesterol, serum LDL, serum HDL, peripheral lipoprotein lipase activity and the intravenous fat tolerance test. No other toxicological side effects were seen.

Adult↗

Downregulation of the heat shock response is independent of DnaK and sigma32 levels in Caulobacter crescentus.

Expression of heat shock genes in Gram-negative proteobacteria is positively modulated by the transcriptional regulator RpoH, the sigma(32) subunit of RNA polymerase (RNAP). In this study we investigated the chaperones DnaK/DnaJ and GroES/GroEL as possible modulators of the heat response in Caulobacter crescentus. We have shown that cells overexpressing DnaK show poor induction of heat shock protein (HSP) synthesis, even though sigma(32) levels present a normal transient increase upon heat stress. On the other hand, depletion of DnaK led to higher levels of sigma(32) and increased transcription of HSP genes, at normal growth temperature. In contrast, changes in the amount of GroES/EL had little effect on sigma(32) levels and HSP gene transcription. Despite the strong effect of DnaK levels on the induction phase of the heat shock response, downregulation of HSP synthesis was not affected by changes in the amount this chaperone. Thus, we propose that competition between sigma(32) and sigma(73), the major sigma factor, for the core RNAP could be the most important factor controlling the shut-off of HSP synthesis during recovery phase. In agreement with this hypothesis, we have shown that expression of sigma(73) gene is heat shock inducible.

Caulobacter crescentus↗