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Biomedical subjects

J Chai

Publications and source records attributed to J Chai.

At least 37 records · Page 2Linked to original sources
PubMed2001

Crystal structure of a phosphorylated Smad2. Recognition of phosphoserine by the MH2 domain and insights on Smad function in TGF-beta signaling.

Ligand-induced phosphorylation of the receptor-regulated Smads (R-Smads) is essential in the receptor Ser/Thr kinase-mediated TGF-beta signaling. The crystal structure of a phosphorylated Smad2, at 1.8 A resolution, reveals the formation of a homotrimer mediated by the C-terminal phosphoserine (pSer) residues. The pSer binding surface on the MH2 domain, frequently targeted for inactivation in cancers, is highly conserved among the Co- and R-Smads. This finding, together with mutagenesis data, pinpoints a functional interface between Smad2 and Smad4. In addition, the pSer binding surface on the MH2 domain coincides with the surface on R-Smads that is required for docking interactions with the serine-phosphorylated receptor kinases. These observations define a bifunctional role for the MH2 domain as a pSer-X-pSer binding module in receptor Ser/Thr kinase signaling pathways.

Amino Acid Motifs↗
PubMed2001

Cardiomyopathy in transgenic mice with cardiac-specific overexpression of serum response factor.

Serum response factor (SRF), a member of the MCM1, agamous, deficiens, SRF (MADS) family of transcriptional activators, has been implicated in the transcriptional control of a number of cardiac muscle genes, including cardiac alpha-actin, skeletal alpha-actin, alpha-myosin heavy chain (alpha-MHC), and beta-MHC. To better understand the in vivo role of SRF in regulating genes responsible for maintenance of cardiac function, we sought to test the hypothesis that increased cardiac-specific SRF expression might be associated with altered cardiac morphology and function. We generated transgenic mice with cardiac-specific overexpression of the human SRF gene. The transgenic mice developed cardiomyopathy and exhibited increased heart weight-to-body weight ratio, increased heart weight, and four-chamber dilation. Histological examination revealed cardiomyocyte hypertrophy, collagen deposition, and interstitial fibrosis. SRF overexpression altered the expression of SRF-regulated genes and resulted in cardiac muscle dysfunction. Our results demonstrate that sustained overexpression of SRF, in the absence of other stimuli, is sufficient to induce cardiac change and suggest that SRF is likely to be one of the downstream effectors of the signaling pathways involved in mediating cardiac hypertrophy.

Actins↗
PubMed2001

[Evaluation of radiation dose and radiation risk for dental patients].

1. The collective dental radiation dose in Israel in 1998 is 42.86 Sv. 2. The collective dental radiation is responsible for a mortality of about 2.14 people per year in Israel, and a similar number of morbidity from non-lethal cancer. 3. It seems that the quality of the picture in dental radiographs in Israel is not satisfactory, so is the dentists' level of knowledge about it. 4. Exposure to dental radiographs may be reduced by half if measures are taken to ensure the quality of the radiographs and the knowledge of dentists on the subject.

Clinical Competence↗
PubMed2001

[Changes in plasma free amino acid concentrations in rats during sepsis].

OBJECTIVE: To explore the relationship between plasma free amino acid concentrations and skeletal muscle proteolysis in rats during sepsis. METHODS: An animal model of sepsis in rats was established by administering endotoxin into the peritoneal cavity. The plasma concentrations of free amino acid, ALT, AST, cortisol, TNF-alpha and IL-6 were determined. The rats were randomly divided into normal control, 2, 6, 12 and 24 h groups after administration of endotoxin(8 rats for each group). RESULTS: The total plasma free amino acids concentrations fluctuate within normal range within 24 h after administration of endotoxin. A marked decrease in BCAA (branch-chainamino acid) was observed at 2, 6 and 12 h after administration of endotoxin, but aromatic amino acids (AAA) increased in varying degrees. BCAA/AAA was lower at 2 h and 6 h as compared with that of the normal control, while Phe/Tyr increased obviously at every time point. Lys, Sar, Cys and P-Ser showed no significant changes within 24 h after the administration of endotoxin. Thr, Glu, Orn, His, 3-MH and Ala increased during sepsis, and other amino acids more or less decreased. Plasma concentrations of ALT, AST, cortisol, TNF-alpha and IL-6 obviously increased within 24 h after the administration of endotoxin(P < 0.01). Cortisol peaked at 6 h and IL-6 peaked at 12 h, while TNF-alpha at 2 h. CONCLUSION: The results suggested that metabolic disorder of plasma free amino acids during sepsis is due to enhancement of skeletal muscle proteolysis and liver overloading.

Alanine Transaminase↗
PubMed2001

[Effect of sepsis on the expression of ubiquitin and ubiquitinated protein in rat skeletal muscle].

OBJECTIVE: To study the regularity of ubiquitin and ubiquitinated protein expression in rat skeletal muscle during sepsis, and the molecular mechanism of enhancement in skeletal muscle protein catabolism. METHODS: Wistar rats with sepsis were administered endotoxin peritoneally. The rats were randomly divided into 4 groups rats: 2, 6, 12 and 24 h after administration of endotoxin; each group (16) included normal controls. In vitro muscle incubation system with sufficient oxygen supply was used with amino acid automatic analyzer for detecting the proteolytic rate of the extensor digitorium longus(EDL) and soleus(SOL) muscle in the sample. The expression of ubiquitin and ubiquitinated protein in rat EDL muscle was determined by western blot. RESULTS: Total proteolytic rate in the EDL muscle increased slightly at 2 and 6 h after administering endotoxin into the peritoneal cavity, and no significant difference at 12 and 24 h was observed. There was a progressive increase of 155% and 220% in myofibrillar proteolytic rate at 2 and 6 h, and 40% at 12 h, respectively, as compared with that of the normal controls. The expression of ubiquitin and ubiquitinated protein in the EDL muscle rose by 46% and 2.4 fold at 2 h and 6 h after administering endotoxin, while the ubiquitinated protein of high molecular weight was determined. No significant changes were noted in the expression of ubiquitin and ubiquitinated protein at 12 and 24 h. CONCLUSION: The results indicate that activation of ubiquitin-proteasome pathway occurs in rat skeletal muscle during sepsis, and high expression of ubiquitin and ubiquitinated protein means that the substrate flowing into ubiquitin-proteasome pathway increases markedly, and then leads to muscle wasting.

Animals↗
PubMed2001

[The experiences in correction of cicatricial foot drop in 28 patients].

OBJECTIVE: To summarize the experiences in correction of cicatricial foot drop. METHODS: 37 cicatricial drop feet in 28 postburn patients were treated in recent 4 years. The cicatricial flap survival rate was documented to compare the effects of two surgical designs, the different intervals from burn to the operation and three surgical methods used in early burn stage. RESULTS: All of the 37 wounded feet got satisfactory correction. There was no significant statistic difference in flap survival between the two surgical designs. More necrosis of the flap was observed in patients who received early escharectomy (including full thickness skin and fat) or had been burned for less than 1.5 years. CONCLUSIONS: The reverse design of the Achilles tendon flap for correction of drop foot was as safe and effective as a routine design. The operation method used in early burn stage and the interval from burn to the corrective operation should be considered in cicatricial flap design.

Achilles Tendon↗
PubMed2001

[The effects of extensive excision of massive invasive infected burn wound on the REE of burn patients with sepsis].

OBJECTIVE: To explore the effects of extensive excision of massive invasive infected burn wound on the REE of burn patients with sepsis. METHODS: REEs and plasma levels of IL -- 6, IL -- 8, TNFalpha and LPS were determined before and after surgical interventions and when patients', condition improved in 8 burned cases with sepsis. RESULTS: All the 8 patients survived after treatment. The REE level in patients after operation was significantly lower than those before the operation (P < 0.01). REE in patients whose condition improved decreased obviously when compared to that after operation (P < 0.01). The plasma levels of IL -- 6, IL -- 8, TNFalpha and LPS decreased markedly after the operation when compared to those before operation (P < 0.05). and there were lower levels of these factors when the patients', condition improved (P < 0.001). Furthermore, there were closely positive correlations between REE and plasma IL -- 6, IL -- 8, TNFalpha and LPS (P < 0.01). CONCLUSION: Over -- releasing of some inflammatory mediators could be corrected by means of extensive excision of massive invasively infected burn wound. This might be beneficial to the control or the amelioration of the hypermetabolism in burn patients with sepsis.

Adolescent↗
PubMed2001

[The change in plasma concentration of free amino acids during early postburn stage in severely scalded rats].

OBJECTIVE: To investigate the rule of the change in plasma concentration of free amino acids during early postburn stage in severely scalded rats, so as to provide assistance for the study of postburn abnormal metabolism of skeletal muscle. METHODS: Male Wistar rats inflicted by 30% TBSA III degree scalding were employed as the model and were randomly divided into normal (C), 2 postburn hour (PBH), 6PBH, 12PBH and 24PBH groups, with 8 rats in each group. Plasma concentrations of free amino acids was determined by automatic amino acid analyzer. At the same time, the plasma contents of alanine aminotransferase (ALT), aspartate aminotransferase (AST), cortisol, TNF and IL-6 were also assayed. RESULTS: There was adecreasing tendency in varying degrees in plasma concentration of all amino acids at each time points within 24 PBHs although there was no obvious difference in total amino acids content at each time point. The plasma level of BCAA decreased evidently at 2 PBH and increased obviously at 12 PBH, while the plasma levels of aromatic amino acids (AAA) increased evidently at 12 and 24 PBHs. In addition, the BCAA/AAA ratio showed no change. The ratio of phenylalanine to tyrosine increased significantly at all postburn time points except that of 2PBH. The plasma levels of ALT, AST increased obviously at all postburn time points (P < 0.01). Plasma cortisol levels in all scalding groups were markedly higher than that in C group (P < 0.01), and reached peak level at 12 PBH. Plasma contents of TNFalpha and IL-6 increased significantly (P < 0.01). Whereas the changes in IL-6 and cortisol were obviously and positively correlated to the changes in 3 -- mH and Phe/Tyr. CONCLUSION: There were significant changes in plasma contents of free amino acids during early postburn stage in scalded rats, which might be related to the early excessive release of inflammatory mediators and enhanced degradation of skeletal muscle and impairment of hepatic function. The mechanism of the change needs to be further studied.

Alanine Transaminase↗
PubMed2000

Structural and biochemical basis of apoptotic activation by Smac/DIABLO.

Apoptosis (programmed cell death), an essential process in the development and homeostasis of metazoans, is carried out by caspases. The mitochondrial protein Smac/DIABLO performs a critical function in apoptosis by eliminating the inhibitory effect of IAPs (inhibitor of apoptosis proteins) on caspases. Here we show that Smac/DIABLO promotes not only the proteolytic activation of procaspase-3 but also the enzymatic activity of mature caspase-3, both of which depend upon its ability to interact physically with IAPs. The crystal structure of Smac/DIABLO at 2.2 A resolution reveals that it homodimerizes through an extensive hydrophobic interface. Missense mutations inactivating this dimeric interface significantly compromise the function of Smac/DIABLO. As in the Drosophila proteins Reaper, Grim and Hid, the amino-terminal amino acids of Smac/DIABLO are indispensable for its function, and a seven-residue peptide derived from the amino terminus promotes procaspase-3 activation in vitro. These results establish an evolutionarily conserved structural and biochemical basis for the activation of apoptosis by Smac/DIABLO.

Amino Acid Sequence↗
PubMed2000

Heparin-free hemodialysis in the treatment of hypernatremia in severely burned patients.

BACKGROUND: Hypernatremia in severely burned patients is associated with high morbidity and mortality rates. As the causes of hypernatremia in major burn patients are still not clear, hemodialysis is the method of choice for the treatment. While hemodialysis is effective for the control of hypernatremia, it can cause bleeding complications that may be fatal for burn patients with extensive wounds and potential gastro-intestinal mucosal damage. CLINICAL DATA: In the present study heparin-free hemodialysis in which the heparin is firmly absorbed to the haemofiltration membrane, hemophan, dispensed with systemic use of heparin. In two extensively burned patients with burn area of 100% TBSA and 98% TBSA respectively and hypernatremia with serum sodium concentration as high as 169 and 158 mmol/l respectively, heparin-free hemodialysis was performed five times and three times each. RESULTS: Hypernatremia was satisfactorily corrected with no interference to the coagulation system in the two patients as indicated by clinical observation and biochemical analysis. The patient with burn area of 98% TBSA survived and the patient with burn area of 100% TBSA died of wound coverage failure 6 weeks after injury because of non-availability of autograft. CONCLUSION: Heparin-free hemodialysis is an effective and safe method in the treatment of hypernatremia in extensively burned patients.

Adult↗
PubMed2000

Photophysical processes of a copolymer containing naphthalene and carbazole rings.

The photophysical processes of copolymer formed by copolymerization of beta-naphthyl-methacrylate (NMA) with vinylcarbazole (VCZ) were studied. The results show that when the solution of copolymer (NMA-VCZ) in THF is located in a low concentration range (about 10(-8) mol/l), the fluorescence emission is in good agreement with that of NMA monomer and the excimer is formed with gradual increase in concentration of copolymer (NMA-VCZ). The fluorescence of copolymer (NMA-VCZ) can be efficiently quenched both by electron donors and acceptors where the quenching effects follow the Stern-Volmer equation. The dimolecular exciplex between copolymer (NMA-VCZ) and N,N-dimethylaniline (DMA) is formed and the triple exciplex is also observed in the same system.

Carbazoles↗
PubMed2000

[Exclusive mapping on polydactyly with markers on chromosome 7 and 2 in a Chinese kindred].

OBJECTIVE: This study was aimed at mapping polydactyly related genes in a Chinese kindred. METHODS: Linkage analysis was performed using 7 markers on chromosome 7 and 1 marker on chromosome 2. RESULTS: Pairwise linkage analysis showed no linkage between the markers and polydactyly related gene in the kindred. CONCLUSION: The polydactyly related gene in this kindred may be located on a new locus.

Chromosome Mapping↗
PubMed2000

Mitochondrial gene variation in type 2 diabetes mellitus: detection of a novel mutation associated with maternally inherited diabetes in a Chinese family.

OBJECTIVE: To explore the relationship between type 2 diabetes mellitus and the mutation(s) in mitochondrial DNA. METHODS: According to the previous literature, the fragment of mitochondrial DNA from nucleotide 3153 to 3551, which had shown high frequency of point mutation, was scanned with the technique of polymerase chain reaction--single strand conformation polymorphism (PCR-SSCP) in Chinese normal control, type 2 diabetic population, and 12 families suffered from maternally inherited type 2 diabetes mellitus. Direct sequencing was applied to detect the fragments with abnormal conformation. RESULTS: No special band was found in SSCP electrophoreses in Chinese normal control, and only one subject (No. 81) of diabetic population indicated the abnormality in SSCP study, which was affirmed to be a silent point mutation of T to C at nucleotide 3336 inducing no change in amino acid (ATT-->ATC, Ile). Pedigree 25,001 was the only family that exhibited strongly different SSCP characteristic from the other 11 ones, which was confirmed to be caused by a single point mutation mt3285T-->C/T in the coding region of tRNA(Leu(UUR)) gene by the technique of direct sequencing. CONCLUSIONS: The variation within mt DNA 3153-3551 is not the major cause of type 2 diabetes in Chinese population suffered from this disease in this study. The point mutation T-->C/T at the mitochondrial nucleotide 3285, which was found in pedigree 25,001, is located in the highly conservative region of tRNA(Leu(UUR)) gene. It is strongly suggested that this mutation cause the conversion in the 3-dimentional structure of tRNA(Leu(UUR)), which might disturb the normal translation and lead to the impairment in mitochondrial oxidative phosphorylation characterized by the defects of the polypeptides involved in the respiratory chain. Thus, insulin secretion deficiency and insulin resistance might occur.

Adult↗
PubMed2000

Successful treatment of invasive burn wound infection with sepsis in patients with major burns.

OBJECTIVE: To investigate the clinical characteristics of invasive burn wound infection with sepsis in patients with major burns and to summarize the successful experiences in the treatment of such patients. METHODS: Eight patients with major burns, complicated by invasive burn would infection and sepsis were consecutively admitted to our hospital from September 1997 to October 1998. Among them, 6 patients developed multiple organ dysfunction syndrome (MODS) and 2 developed septic shock. The plasma concentrations of IL-6, IL-8, TNF alpha and lypopolysaccharide (LPS) were assayed before and after surgical intervention, as well as when the patient's vital signs became stable. RESULTS: The patients' conditions usually deteriorated abruptly when extensive invasive burn wound infection emerged. While multi-microbial infection was usually found, Pseudomonas aeruginosa was the predominant bacteria isolated from the subeschar tissue. The plasma concentrations of IL-6, IL-8, TNF alpha and LPS before surgical intervention were significantly higher than those after surgical intervention (P < 0.05). The lowest levels of the inflammatory mediators were observed when the patients' conditions became stable, and the values were significantly lower than those before surgical intervention (P < 0.001). CONCLUSION: Since the main cause of burn wound sepsis is the presence of a large area of infected burn wound, they should be excised and covered as early as possible. LPS and pro-inflammatory mediators play an important role in the pathogenesis of burn sepsis. Although favorable results should be attributed to comprehensive treatment, we believe that early, aggressive and thorough surgical excision of infected burn wounds, followed by sound and complete coverage of the area, play a crucial role.

Adolescent↗
PubMed2000

Effect of extensive excision of burn wound with invasive infection on hypermetabolism in burn patients with sepsis.

OBJECTIVE: To evaluate the effect of extensive excision of invasive burn wound infection on hypermetabolic response in burn patients with sepsis. METHODS: Eight patients with major burn, complicated by invasive burn wound infection and sepsis, were consecutively admitted to our hospital from September 1997 to October 1998. Resting energy expenditures (REEs) were monitored by means of cardiorespiratory diagnostic system (Medical Graphics Corporation, USA) at patients' bedside. Plasma concentration of IL-6, IL-8, TNF-alpha, and LPS were assayed before and after surgical intervention and at the time when the patients' vital signs became stable. Correlation analysis between REEs and IL-6, IL-8, TNF-alpha, and LPS were made, respectively. RESULTS: A total of 8 treated patients survived. Values of REE before surgical intervention were significantly higher than those after surgical intervention (P < 0.01), and when patients' vital signs became stable the values were significantly lower than those after surgical intervention (P < 0.01). The plasma concentrations of IL-6, IL-8, TNF-alpha, and LPS after excision of invasive burn wound infection were significantly lower than those before surgical intervention (P < 0.05). The lowest levels of these inflammatory mediators were observed when the conditions of patients became stable, and the values were significantly lower than those before surgical intervention (P < 0.001). There was a significant positive correlation between REE level and respective values of plasma IL-6, IL-8, TNF-alpha, and LPS (P < 0.01). CONCLUSIONS: It seemed that the extensive excision of invasively infected burn wound in patients with major burn should be performed as early as possible to reduce an increased release of inflammatory mediators and to control the hypermetabolic response during sepsis.

Adolescent↗
PubMed2000

[Prevention and treatment of MODS in severely burned patients: an institute based retrospective study].

OBJECTIVE: To determine if the preventive and treatment measures developed from basic and clinical research work have any effects on the incidence and outcome of MODS in severely burned patients. METHODS: 657 extensively burned patients (burn size exceeding 30% TBSA) admitted to the clinical department from January 1970 through October 1999 were studied. The morbidity and mortality rates were compared in patient groups hospitalized before and after January 1990 when major preventive and treatment measures began to be extensively executed. These measures consisted of prompt, rapid and adequate fluid resuscitation, restoration of bowel blood supply with anisodamine (654 - 2), use of oxygen free radical scavengers (e.g. mannitol, vitamin C and E), extensive escharectomy during shock stage, early tube feeding, support of organ function, etc. RESULTS: Before 1990 when very few preventive and treatment measures were applied, the incidence of MODS, 17.3% (64 out of 369), and the death rate 87.5% (56 out of 64). After 1990, with the application of various preventive measures and treatment, the morbidity and mortality rates were reduced to 6.9% (20/288) and 40.0% (8/20), respectively. CONCLUSION: Our results suggest that measures which mitigate or eliminate the predisposing and causative factors of MODS may be salutary in the prevention and treatment of MODS after extensive burn injury.

Adolescent↗