Recovery of motor and language abilities after stroke: the contribution of functional imaging

In recent years, functional imaging techniques, like functional magnetic resonance imaging (fMRI), positron emission tomography (PET), and transcranial magnetic stimulation (TMS), have shown that the improvement of motor and language function after ischemic stroke is accompanied by extensive reorganizational changes in the human cortex. To better understand these changes and to judge to what extent they could be responsible for clinical improvement, some basic principles of the organization of the motor and language system are discussed.Non-invasive functional imaging can have only a limited contribution in determining which of the possible underlying neural mechanisms, as they are known from animal experiments, play a role in functional recovery. However, they make it possible to define the functional consequences of anatomical lesions in individual patients and to correlate these functional consequences in the motor and language system with the clinical deficit. They can be used to assess the influence on the cortical reorganization of established and newer physiotherapies, logopedics and medical intervention, and they could be a useful tool in determining prognosis.     

Antigen-specific production of interleukin (IL)-13 and IL-5 cooperate to mediate IL-4Ralpha-independent airway hyperreactivity

The pathogenesis of human asthma and the development of key features of pulmonary allergy in mouse models has been critically linked to IL-13. Analyses of the receptor components employed by IL-13 have shown that delivery of this cytokine to the airways of naive IL-4Ralpha gene targeted (IL-4Ralpha(-/-)) mice fails to induce disease, suggesting that this membrane protein is critical for transducing IL-13-mediated responses. The current study demonstrates that, in contrast to naive mice, T helper 2 bias, airways hyperreactivity (AHR) and tissue eosinophilia develop in Ovalbumin-sensitized IL-4Ralpha(-/-) mice and that these responses can be inhibited by the IL-13 antagonist sIL-13Ralpha2Fc. Therefore, antigen stimulation induces an IL-13-regulated response that is independent of IL-4Ralpha. To determine the role of IL-5 and eosinophils in the development of disease in antigen-exposed IL-4Ralpha(-/-) mice, pulmonary allergy was examined in mice deficient in both factors. IL-4Ralpha/IL-5(-/-) mice were significantly defective in their ability to produce IL-13 and failed to develop AHR, suggesting that IL-5 indirectly regulates AHR in allergic IL-4Ralpha(-/-) mice by an IL-13-dependent mechanism. Collectively, these results demonstrate that IL-13-dependent processes regulating the development of AHR and T helper bias persist in the in the lungs of allergic IL-4Ralpha(-/-) mice.     

Effects of priming duration on retention over the first 1 1/2 years of life

Exposing individuals to an isolated component (a prime) of a prior event alleviates its forgetting. Two experiments with 120 human infants between 3 and 18 months of age determined the minimum duration of a prime that can reactivate a forgotten memory and how long the reactivated memory persists. Infants learned an operant task, forgot it, were exposed to the prime, and later were tested for renewed retention. In Experiment 1, the minimum duration of an effective prime decreased logarithmically with age, but was always longer than the duration of a mere glance. In Experiment 2, the reactivated memory was forgotten twice as fast after a minimum-duration prime as after a full-length one, irrespective of priming delay and infant age. These data reveal that the minimum effective prime duration psychophysically equates the accessibility of forgotten memories. We conclude that priming is perceptually based with effects that are organized on a ratio (log) scale.     

Plant foods and colon cancer: an assessment of specific foods and their related nutrients (United States)

Plant foods have been associated inversely with colon cancer. Since amajor focus of this study was to identify components of plant foods whichmay account for their association with colon cancer, nutrients which arecommonly found in plant foods also were evaluated. A population-basedcase-control study was conducted in Northern California, Utah, and the TwinCities area of Minnesota (United States). Complete data were available frominterviewer-administered questionnaires on 1,993 cases and 2,410 controls.Higher intakes of vegetables (for highest relative to lowest quintile ofintake) were associated inversely with colon cancer risk: the odds ratio(OR) was 0.7 for both men (95 percent [CI] confidence interval = 0.5-0.9)and women (CI = 0.5-1.0). Associations were stronger among those withproximal tumors. Total fruit intake was not associated with colon cancerrisk although, among men, higher levels of whole grain intake wereassociated with a decreased risk (OR = 0.6, CI = 0.4-0.9 for older men);high intakes of refined grains were associated with an increased risk (OR =1.5, CI = 1.1-2.1). Dietary fiber intake was associated with a decreasedrisk of colon cancer: OR = 0.5 (CI = 0.3-0.9) for older men; OR = 0.7 (CI =0.4-1.2) for older women; OR = 0.6 (CI = 0.4-1.0) for men with proximaltumors; OR = 0.5 (CI = 0.3-0.9) for women with proximal tumors. Othernutrients, for which plant foods were the major contributor - such asvitamin B6, thiamin, and niacin (women only) - also were associatedinversely with colon cancer. Neither beta-carotene nor vitamin C wasprotective for colon cancer. Adjustment of plant foods for nutrients foundin plant foods or for supplement use did not appreciably alter the observedassociations between plant foods and colon cancer.     

Effect of ileal oleate on interdigestive intestinal motility of the dog

To determine the effect of ileal oleate on fasting intestinal motility, pairs of duodenal and ileal catheters and bipolar duodenal and jejunal seromuscular electrodes were surgically implanted in six dogs. The ileum was perfused with either normal saline (154 mM NaCl) or oleic acid emulsion (152 mM), while intestinal myoelectric activity was continuously monitored. For transit studies, a bolus of [³H]PEG was injected into the duodenum, and jejunal and ileal alliquots were collected every 15 min for a 6-hr study period. Plasma samples were collected for radioimmunoassays of peptide YY and enteroglucagon. Ileal oleate infusion increased the MMC cycle length and decreased the number of MMCs (P<0.001) and the myoelectric spike-burst frequency/10 min in the duodenum (P<0.05). Both duodenal-jejunal (P<0.05) and duodenal-ileal transit (P<0.01) were delayed markedly by ileal perfusion with oleic acid emulsion as compared to control studies. Ileal oleate increased plasma levels of peptide YY (P<0.01) and enteroglucagon (P<0.01). Ileal perfusion with oleate therefore activated the so-called ileal brake, diminishing duodenal myoelectric spike bursts and slowing intestinal transit while concurrently increasing plasma levels of peptide YY and enteroglucagon.Dr. Dreznik is currently at Tel Aviv University, Tel Aviv, Israel, at the Sackler Faculty of Medicine.An abstract of this work was presented at the Forum of Fundamental Problems at the American College of Surgeons meeting in October 1991.Supported by the V.A. Research Advisory Group, NIH Biomedical Research Support Grant.     

Phase I-II study: triciribine (tricyclic nucleoside phosphate) for metastatic breast cancer

Triciribine is a purine analogue which inhibits DNA and protein synthesis. We performed two studies to define its activity against metastatic breast cancer. The first study was a phase II study in 14 patients with metastatic breast cancer who had received two or fewer chemotherapy treatments. The treatment schedule was triciribine 20 mg/m² per day by 24-h infusion (CI) daily for 5 days every 6 weeks as recommended by a previous open phase I trial. When neither response nor toxicity was seen in the phase II trial, we assumed the starting dose was too low for this group of patients with good performance status and repeated the phase I trial in patients with metastatic breast cancer with good performance status. The starting dose was 35 mg/m² per day using the same 5-day CI schedule, and starting doses were increased in subsequent cohorts of three patients in increments of 5 mg/m² until toxicity occurred. In the initial (phase II) study, one patient had stable disease for 18 weeks (three courses), the remainder progressed. There were no significant toxic effects. In the subsequent phase I study, ten patients were treated until the study was closed The maximum dose was 40 mg/m². Two patients died, one each at the 35 and 40 mg/m² levels, respectively, 3 months and 6 weeks after their last course, one without interveing disease progression. Both had severe hypertriglyceridemia (18- and 21-fold elevation) and severe fatigue. At postmortem examination, one had congestive cardiomyopathy, and the other had severe pancreatitis and hypothyroidism. One patient had severe exacerbation of psoriasis which made her bedridden for more than 30 days. Four patients had hyperglycemia. Plasma pharmacology studies showed erratic drug levels, presumably related to enterohepatic circulation. Postmortem pharmacology studies showed residual drug present as long as 12 weeks after the last dose. We conclude that triciribine is ineffective at all doses tested and at doses of 35 mg/m² has unacceptable toxic effects.This work was performed under National Cancer Institute contract 1-CM-57739     

Soybean isoflavones, genistein and genistin, inhibit rat myoblast proliferation, fusion and myotube protein synthesis.

The isoflavones, genistein and genistin, are cytotoxic in vitro (e.g. , inhibition of cell proliferation), due in part to inhibition of protein tyrosine kinase and DNA topoisomerase activities. Normal cell functions associated with these enzymatic activities could potentially be impaired in animals through ingestion of soybean products. In this study, cultured rat myogenic cells (L8) were used to determine whether genistein or genistin influences myoblast proliferation and fusion, and myotube protein synthesis and degradation. Genistein or genistin was dissolved in dimethylsulfoxide and included in the culture medium at 0, 1, 10 or 100 micromol/L. Myoblast proliferation was measured by methyl-3H-thymidine incorporation over 48 h. Myoblast differentiation was evaluated by the number of nuclei in multinucleated myotubes. Myotube protein synthesis was measured by 2-h 3H-amino acid incorporation into the myosin and total protein pools after acute (2 h) or chronic (24 h) exposure to similar treatments; protein degradation was measured by measuring radioactivity in protein pools following a time course of protein breakdown after myotube proteins were prelabeled with 3H-amino acids. Genistein or genistin strongly inhibited in vitro myoblast proliferation (P < 0.001) and fusion (P < 0.001) in a dose-dependent manner with effective genistein concentration as low as 1 micromol/L. Genistein or genistin inhibited protein accretion in myotubes (P < 0.001). Decreased protein accretion is largely a result of inhibition on cellular (myofibrillar) protein synthesis rate. No adverse effect on protein degradation was observed. Results suggest that if sufficient circulating concentrations are reached in tissues of animals consuming soy products, genistein/genistin can potentially affect normal muscle growth and development.     

Ovarian tissue grafting: Lessons learnt from our experience with 55 grafts

Purpose

Uncertainties remain regarding the clinical efficacy of ovarian tissue cryopreservation and grafting. We report a retrospective analysis of reproductive outcomes and lessons learnt following 55 ovarian tissue transplant procedures at our center from 2006 to 2019.

Methods

We analyzed variables related to graft success such as tissue volume, follicular density, total follicular volume, and age on the duration of graft function.

Results

Follicular density and total follicular volume correlate positively with duration of graft function. All clinical pregnancies in our cohort occurred in women who were aged 35 or less at the time of ovarian tissue cryopreservation.

Conclusion

Graft success, as determined by eventual pregnancy and the longevity of graft function, may be impacted by factors including age at cryopreservation, follicular density, and total follicular volume.