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Biomedical subjects

S Y Fu

Publications and source records attributed to S Y Fu.

13 recordsLinked to original sources
PubMed1996

Phosphorylation of the carboxyl-terminal region of dystrophin.

Dystrophin is a protein product of the gene responsible for Duchenne and Becker muscular dystrophy. The protein is localized to the inner surface of sarcolemma and is associated with a group of membrane (glyco)proteins. Dystrophin links cytoskeletal actins via the dystrophin-associated protein complex to extracellular matrix protein, laminin. This structural organization implicates the role of dystrophin in stabilizing the sarcolemma of muscle fibers. Precisely how dystrophin functions is far from clear. The presence of an array of isoforms of the C-terminal region of dystrophin suggests that dystrophin may have functions other than structural. In agreement, many potential phosphorylation sites are found in the C-terminal region of dystrophin, and the C-terminal region of dystrophin is phosphorylated both in vitro and in vivo by many protein kinases, including MAP kinase, p34cdc2 kinase, CaM kinase, and casein kinase, and is dephosphorylated by calcineurin. The C-terminal domain of dystrophin is also a substrate for hierarchical phosphorylation by casein kinase-2 and GSK-3. These observations, in accordance with the finding that the cysteine-rich region binds to Ca2+, Zn2+, and calmodulin, suggest an active involvement of dystrophin in transducing signals across muscle sarcolemma. Phosphorylation-dephosphorylation of the C-terminal region of dystrophin may play a role in regulating dystrophin-protein interactions and (or) transducing signal from the extracellular matrix via the dystrophin molecule to the cytoskeleton.

Animals↗
PubMed1995

Characterization of the recombinant C-terminal domain of dystrophin: phosphorylation by calmodulin-dependent protein kinase II and dephosphorylation by type 2B protein phosphatase.

We report that the C-terminal domain of skeletal muscle dystrophin expressed as a fusion protein with glutathione S-transferase (designated GST-CT-1) is a substrate for Ca2+/calmodulin-dependent phosphorylation and dephosphorylation. GST-CT-1 and GST-CT-1F (GST-CT-1 truncated by 20-25 residues) were phosphorylated by Ca2+/calmodulin-dependent protein kinase II (CaM kinase II). The stoichiometries of phosphorylation by CaM kinase II were 1.65 mol of Pi/mol of GST-CT-1 and 0.39 mol of Pi/mol of GST-CT-1F, respectively, suggesting that the principal site(s) of phosphorylation is (are) located in the C-terminal 20-25 residues that are missing from GST-CT-1F. The GST-CT-1 fusion protein was phosphorylated on both serine and threonine residues, whereas GST-CT-1F was phosphorylated only on serine. CaM kinase II-phosphorylated GST-CT-1 and GST-CT-1F were efficiently dephosphorylated by calcineurin, a Ca2+/calmodulin-dependent protein phosphatase (type 2B protein phosphatase). Importantly, calcineurin was found to be associated with a purified sarcolemmal membrane preparation enriched in dystrophin. Type 2A protein phosphatase isolated from smooth muscle (SMP-I) and its catalytic subunit (SMP-ic) also dephosphorylated GST-CT-1, but were less active toward these substrates than was calcineurin. Type 2C phosphatase (SMP-II) and type 1 protein phosphatases [SMP-III, SMP-IV, and myosin-associated phosphatase (PP1M) of smooth muscle and skeletal muscle protein phosphatase 1c] were ineffective in dephosphorylating the C-terminal region of dystrophin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Contributing factors to poor functional recovery after delayed nerve repair: prolonged axotomy.

The contribution of prolonged motoneuron axotomy to the poor functional recovery after delayed nerve repair was determined by means of a nerve cross-anastomosis paradigm in the rat. The tibial nerve was axotomized up to 12 months before it was cross-sutured to the distal stump of the freshly cut common peroneal nerve to innervate the freshly denervated tibialis anterior muscle. Three to 17 months later, muscle and motor unit (MU) forces were measured to quantify the number of axons that had successfully regenerated and reinnervated the muscle. The extent of axonal branching was estimated by the innervation ratio (IR) (i.e., the number of muscle fibers innervated by each axon), which was obtained directly by counting muscle fibers in a single glycogen-depleted MU in each muscle and indirectly by calculation. The total number of MUs in each muscle significantly decreased with progression of axotomy and was only 35% of the control when axotomy was prolonged more than 3 months. Concurrently, MU force and IR increased exponentially, with a mean increase of threefold when axotomy was more than 3 months, which largely compensated for the reduction in the number of axons that reinnervated the muscle. Consequently, muscles reinnervated by tibial motor axons that had been axotomized up to 12 months produced as much force as those reinnervated by freshly axotomized tibial motor axons. Muscle weight, size, and muscle fiber size were similar to those after immediate nerve suture. Although prolonged axotomy does not compromise the number of muscle fibers innervated by each axon, it does reduce the capacity of motor axons to regenerate and thus is an important contributing factor to the poor functional recovery in delayed nerve repair.

Anastomosis, Surgical↗
PubMed1995

Contributing factors to poor functional recovery after delayed nerve repair: prolonged denervation.

The effects of prolonged denervation, independent from those of prolonged axotomy, on the recovery of muscle function were examined in a nerve cross-anastomosis paradigm. The tibialis anterior muscle was denervated for various durations by cutting the common peroneal nerve before a freshly cut tibial nerve was cross-sutured to its distal stump. Nerve regeneration and muscle reinnervation were quantified by means of electrophysiological and histochemical methods. Progressively fewer axons reinnervated the muscle with prolonged denervation; for example, beyond 6 months the mean (+/- SE) motor unit number was 15 +/- 4, which was far fewer than that after immediate nerve suture (137 +/- 21). The poor regeneration after prolonged denervation is not due to inability of the long-term denervated muscle to accept reinnervation because each regenerated axon reinnervated three- to fivefold more muscle fibers than normal. Rather, it is due to progressive deterioration of the intramuscular nerve sheaths because the effects of prolonged denervation were simulated by forcing regenerating axons to grow outside the sheaths. Fewer regenerated axons account for reinnervation of less than 50% of the muscle fibers in each muscle and contribute to the progressive decline in muscle force. Reinnervated muscle fibers failed to fully recover from denervation atrophy: muscle fiber cross-sectional area being 1171 +/- 84 microns2 as compared to 2700 +/- 47 microns2 after immediate nerve suture. Thus, the primary cause of the poor recovery after long-term denervation is a profound reduction in the number of axons that successfully regenerate through the deteriorating intramuscular nerve sheaths. Muscle force capacity is further compromised by the incomplete recovery of muscle fibers from denervation atrophy.

Anastomosis, Surgical↗
PubMed1993

Weaning practices and growth in rural Sichuan infants: a positive deviance study.

To understand some of the factors involved in weaning and growth faltering in rural China, a cross-sectional positive deviance study was undertaken among 389 rural 4-12-month-old infants from two townships of a county in Sichuan. The infants' mothers were interviewed about their child-feeding practices and other sociodemographic information, and anthropometric measurements were made on their infants. Positive deviant infants (those growing adequately in environments in which the majority of the children suffer from growth retardation and malnutrition) were identified from the Chinese WAZ-scores calculated from the anthropometric measurements. Feeding practices found to be associated with the better growth of the positive deviant infants included breastfeeding through age 12 months, feeding soybean milk, liver and pork blood products on a more than weekly basis during the ages of 7-9 months, not feeding rice flour (mifen) before age 7 months, and not giving supplements or tonics. Mothers' nutrition knowledge was also associated with positive deviance status. The relevance of the findings is discussed with respect to designing nutrition education interventions for rural Sichuan.

Breast Feeding↗
PubMed1989

Observation on the effect of sodium nitroprusside and dopamine on acute myocardial infarction during hospitalization.

With improvements in cardiac monitoring systems and the effective treatment of arrhythmias, the case-fatality rate of acute myocardial infarction (AMI) has been declining gradually since 1972. But since 1977, despite the great efforts of medical workers in many countries, the lowest case-fatality rate of AMI has still been about 10%. Over many years, our institute has carried out research aimed at improving the treatment of AMI. However, in our institute the case-fatality rate has fluctuated between 15 and 20% in recent years. From March 1986 to January 1987 we adopted a sodium nitroprusside and dopamine intravenous drip in the treatment of 92 cases of AMI and achieved a hospitalization period AMI case-fatality rate of less than 5% (2 patients died). The treatment methods and relevant materials are reported here.

Adult↗
PubMed1989

Correlation study of left atrial pressure and pulmonary rheogram.

In order to observe correlations between LAP and PRG data, we placed small inflated balloons in the left atria of dogs to change LAP. We found good correlations between LAP and Q-6 interval (r = 0.88, P less than 0.001), b-s interval (r = -0.78, P less than 0.001), Hs (r = -0.59, P less than 0.001), Hs X b-s interval (r = -0.65, P less than 0.001), and HD/Hs (r = 0.50, P less than 0.001). The mechanisms of change of these parameters were investigated and corresponding regression equations derived. The authors point out that D wave enlargement and HD/Hs increase are determinant indices of LAP elevation and may be used to estimate LAP and to differentiate LAP elevation from simple pulmonary hypertension. Therefore, we conclude that PRG may reflect changes of pressure or volume in the pulmonary vein and thus provide a noninvasive method of monitoring cardiac preload and the pulmonary cycle. In addition, this research may provide the experimental basis for employing PRG in the study of such pathological processes as mitral valve lesion, left heart failure, etc.

Animals↗
PubMedDate not supplied

The cellular and molecular basis of peripheral nerve regeneration.

Functional recovery from peripheral nerve injury and repair depends on a multitude of factors, both intrinsic and extrinsic to neurons. Neuronal survival after axotomy is a prerequisite for regeneration and is facilitated by an array of trophic factors from multiple sources, including neurotrophins, neuropoietic cytokines, insulin-like growth factors (IGFs), and glial-cell-line-derived neurotrophic factors (GDNFs). Axotomized neurons must switch from a transmitting mode to a growth mode and express growth-associated proteins, such as GAP-43, tubulin, and actin, as well as an array of novel neuropeptides and cytokines, all of which have the potential to promote axonal regeneration. Axonal sprouts must reach the distal nerve stump at a time when its growth support is optimal. Schwann cells in the distal stump undergo proliferation and phenotypical changes to prepare the local environment to be favorable for axonal regeneration. Schwann cells play an indispensable role in promoting regeneration by increasing their synthesis of surface cell adhesion molecules (CAMs), such as N-CAM, Ng-CAM/L1, N-cadherin, and L2/HNK-1, by elaborating basement membrane that contains many extracellular matrix proteins, such as laminin, fibronectin, and tenascin, and by producing many neurotrophic factors and their receptors. However, the growth support provided by the distal nerve stump and the capacity of the axotomized neurons to regenerate axons may not be sustained indefinitely. Axonal regenerations may be facilitated by new strategies that enhance the growth potential of neurons and optimize the growth support of the distal nerve stump in combination with prompt nerve repair.

Animals↗