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Biomedical subjects

Z J Cai

Publications and source records attributed to Z J Cai.

16 recordsLinked to original sources

RNA CUG repeats sequester CUGBP1 and alter protein levels and activity of CUGBP1.

An RNA CUG triplet repeat binding protein, CUGBP1, regulates splicing and translation of various RNAs. Expansion of RNA CUG repeats in the 3'-untranslated repeat of the mutant myotonin protein kinase (DMPK) mRNA in myotonic dystrophy (DM) is associated with alterations in binding activity of CUGBP1. To investigate whether CUGBP1 is directly affected by expansion of CUG repeats in DM tissues, we examined the intracellular status of CUGBP1 in DM patients as well as in cultured cells over expressing RNA CUG repeats. The analysis of RNA-protein complexes showed that, in control tissues, the majority of CUGBP1 is free of RNA, whereas in DM patients the majority of CUGBP1 is associated with RNA containing CUG repeats. Similarly to DM patients, overexpression of RNA CUG repeats in cultured cells results in the re-allocation of CUGBP1 from a free state to the RNA.protein complexes containing CUG repeats. CUG repeat-dependent translocation of CUGBP1 into RNA-protein complexes is associated with increased levels of CUGBP1 protein and its binding activity. Experiments with cyclohexamide-dependent block of protein synthesis showed that the half-life of CUGBP1 is increased in cells expressing CUG repeats. Alteration of CUGBP1 in DM is accompanied by alteration in translation of a transcription factor CCAAT/enhancer-binding protein beta (C/EBPbeta), which has been previously described to be a target of CUGBP1. Analysis of C/EBPbeta isoforms in DM patients with altered levels of CUGBP1 showed that translation of a dominant negative isoform, LIP, is induced by CUGBP1. Results of this paper demonstrate that the expansion of CUG repeats in DM affects RNA-binding proteins and leads to alteration in RNA processing.

Animals↗

Drug dependence and abuse potential of tramadol.

AIM: To assess the drug dependence and abuse liability of tramadol. METHODS: Subjects of opiate addicts with history of tramadol abuse were 219. Physical dependence of tramadol was assessed using opiate withdrawal scale (OWS), psychic dependence was assessed by association test of Addiction Research Center Inventory-Chinese Version (ARCI-CV); the degrees of craving experienced for tramadol was self-reported on visual analogue scale (VAS). RESULTS: The scores of OWS of tramadol were 0.05-1.07; 3 scores on scales in particular being used the identify euphoric effects--MBG, sedative effects--PCAG, and psychotomimetic effects--LSD of ARCI were 7.3, 6.1, and 3.4, respectively (F = 38.1, P < 0.01); 57.1% of tramadol abuse subjects had craving for tramadol (chi 2 = 75.86, P < 0.01). CONCLUSION: Tramadol produced high abuse potential among opiate addicts.

Adult↗

Green fluorescent protein tag for studies of drug-induced translocation of nucleolar protein RH-II/Gu.

We have constructed a human osteogenic sarcoma cell line, U-2 OS/GFP-Gu, that expresses nucleolar RNA helicase RH-II/Gu tagged with green fluorescent protein (GFP). The presence of a GFP tag does not inhibit RNA helicase, RNA folding and ATPase activities of RH-II/Gu protein. The derived cell line responds to cytotoxic agents like the parental cell line U-2 OS. In the presence of either actinomycin D or toyocamycin, the GFP-RH-II/Gu fusion protein translocates from the nucleolus to the nucleoplasm in the same way as the translocation of endogenous RH-II/Gu. The drug-induced translocation of GFP-RH-II/Gu is easily monitored by direct observation of live cells in vivo. This cell line can be used to screen cytotoxic drugs and to study the mechanisms of drug-induced translocation of RH-II/Gu. The cellular localization of RH-II/Gu during the cell cycle-dependent formation of the nucleolus is readily monitored. Real-time results are obtained more quickly without the disadvantages associated with cell fixation and immunofluorescence-based staining.

Biological Transport↗

Exon 5 encoded domain is not required for the toxic function of mutant SOD1 but essential for the dismutase activity: identification and characterization of two new SOD1 mutations associated with familial amyotrophic lateral sclerosis.

Two new mutations in the gene encoding cytoplasmic Cu,Zn superoxide dismutase (SOD1) have been discovered in patients with familial amyotrophic lateral sclerosis (FALS). These mutations result in the truncation of most of the polypeptide segment encoded by exon 5, one by the formation of a stop codon in codon 126 (L126Z) and the other by inducing alternative splicing in the mRNA (splicing junction mutation). These two mutants of SOD1 result in a FALS phenotype similar to that observed in patients with missense mutations in the SOD1 gene, establishing that exon 5 is not required for the novel toxic functions of mutant SOD1 associated with ALS. These mutant enzymes are present at very low levels in FALS patients, suggesting elevated toxicity compared to mutant enzymes with single site substitutions. This increased toxicity likely arises from the extreme structural and functional changes in the active site channel, beta-barrel fold, and dimer interface observed in the mutant enzymes, including the loss of native dismutase activity. In particular, the truncation of the polypeptide chain dramatically opens the active site channel, resulting in a marked increase in the accessibility and flexibility of the metal ions and side chain ligands of the enzyme active site. These structural changes are proposed to cause a decrease in substrate specificity and an increase in the catalysis of harmful chemical reactions such as peroxidation.

Aged↗

Rapid detoxification of heroin dependence by buprenorphine.

AIM: To evaluate the clinical efficacy of buprenorphine (Bup) in treatment of acute heroin withdrawal. METHODS: Bup was given sublingually daily to 60 cases of heroin addicts in 3 groups: low, medium, and high doses. Withdrawal signs and symptoms of heroin were rated by Clinical Institute Narcotic Assessment. Craving for heroin during detoxification was assessed by Visual Analogue Scale. The side effects of Bup was assessed by Treatment Emergent Symptom Scale. RESULTS: The mean daily consumption of Bup in low, medium, and high group was 2.0, 2.9, and 3.6 mg, respectively. Bup not only suppressed objective signs and withdrawal symptoms for heroin withdrawal, but also reduced the duration for heroin detoxification over 7-8 d. CONCLUSION: Bup is an effective and rapid detoxification agent with fewer side effects for treatment of acute heroin withdrawal.

Adult↗

[Clinical assessment of physical dependence potential of dihydroetorphine hydrochloride (DHE)].

This paper reports the DHE substitution clinical trial in 38 heroin addicts. The CINA (Clinical Institute Narcotic Assessment) scale was used to assess physical dependence potential. The CINA scale contains 10 opioid withdrawal signs (nausea, vomiting, gooseflesh, sweating, restlessness, tremor, larcrimation, nasal congestion, yawning, changes in heart rate and systolic blood pressure) and 3 opiate withdrawal symptoms (abdominal pain, muscle pain and feeling hot or cold). For each subject admitted to the Drug Detoxification and Treatment Center his (her) status on each of the 13 items of CINA were immediately rated. Then, naloxone 0.4 mg was injected iv to precipitate withdrawal symptoms and at 5, 10, 15 min after the naloxone injection, the CINA score of each patient was rated again. The differences among the scores of pre- and post-naloxone injection is a measurement of the degree of withdrawal symptoms. Then, a single dose of DHE was administered sublingually to each patient, all withdrawal symptoms disappeared. These results show that DHE can compete with naloxone for opioid receptors. A good dose-response relationship was found between the 100% suppressive withdrawal sign doses of DHE and the degree of withdrawal sign in heroin addicts. The physical dependence potential of DHE given to heroin addicts sublingually was probably more than that of methadone given to heroin addicts orally by making reference to the report of Dr. Peachy.

Administration, Sublingual↗

The functions of sleep: further analysis.

Most theories addressed to the functions of sleep are proposed primarily according to the results in one area of sleep research and may not be compatible with the results in other areas of sleep research. This paper provides a new theory regarding the functions of sleep by integratively analyzing different areas of sleep research. First, it concludes from the phylogenetic studies and other related sleep research that sleep in mammals has at least one obligatory function which cannot be accomplished during waking. It also shows that the synchronized sleep (SS) period plays a critical role in accomplishing the obligatory functions of sleep and that the obligatory functions of sleep are related to the brain. Then it points out that adjusting and reorganizing emotional behaviors is a very important function of SS. Finally, this theory suggests that the gradual accumulation of various randomly learned memories in the limbic structures would inevitably imbalance and disorganize emotional behaviors so that sleep should be developed in evolution to adjust and reorganize emotions and so that the functions of SS for memory and emotional regulation are the obligatory functions of sleep. Although phylogenetic studies suggest that (PS) may not play obligatory functions across all mammals, there is no doubt that, in tight correlation with SS, PS also plays very important roles in memory and emotion which, however, are different from the corresponding SS roles in those mammals possessing PS.

Animals↗

[Experimental study on the principal effects and dependence potential of thiofentanil].

Thiofentanil is a synthetic analgesic with pharmacological effects similar to etorphine hydrochloride (M99). The aim of the present study was to assess its analgesic and immobilization effects and to evaluate its dependence potential in comparison with morphine. The median analgesic dose (AD50) was measured by hot plate method in mice. The median paralytic dose (PD50), as an indicator of immobilization, was tested in rats, rabbits, dogs and monkeys. Results showed that the analgesic potency of this drug was 3260 times that of morphine, 22 times that of fentanyl and 1.5 times that of M99 and the immobilization effect was 2-3 times that of M99. Results from jumping test in mice and physical dependence-producing test in rats (the drug was dissolved in drinking water) showed that thiofentanil possessed physical dependence liability weaker than morphine. Physical dependence was not observed in rats with intravenous injection of one dose each h over a period of 72 h, and also in monkey with 20-week drug medication. The LD50 of thiofentanil was also determined in mice, rats, rabbits, dogs and monkeys in comparison with M99. Results suggest that it should be valuable to develop thiofentanil as an analgesic for clinical use.

Analgesics, Opioid↗

The neural mechanism of declarative memory consolidation and retrieval: a hypothesis.

This paper proposes a new theory addressing the neural mechanism of declarative memory consolidation and retrieval. The premise of the theory is that the cortex is responsible for the storage of declarative memory while the medial temporal lobe is responsible for the consolidation and retrieval of declarative memory. The theory suggests that the medial temporal lobe can only accomplish its functions related to memory by hierarchically and cooperatively regulating the descending limbic system, including the hypothalamus, epithalamus, septum, mammillary bodies and the bed nucleus of the stria terminalis. These descending limbic structures, together with the amygdala, further send efferents to the four ascending NA, 5-HT, DA and ACh systems. It is these four ascending extrathalamic regulatory systems that provide the feedback neural pathways to the cortex and regulate the processes of memory consolidation and retrieval in the cortex. Therefore, the coupling of these descending limbic structures to the ascending NA, 5-HT, DA and ACh systems completes the neural circuits responsible for the consolidation and retrieval of new declarative memories. This neural mechanism of declarative memory consolidation and retrieval is universal to all species in higher mammals.

Animals↗

[Primary plasma cell leukemia--a comprehensive analysis of 44 cases].

Four cases of primary plasma cell leukemia (PPCL) admitted to our hospital from 1959 to 1987 are reported with a review on additional 40 cases reported in China. Comparing with the 57 cases of multiple myeloma (MM) seen in our hospital, the following features were observed in PPCL: (1) The age was younger with a mean of 45.2 years, 34.1% of the patients were under 40 years. (2) Onset was abrupt. Duration from onset to diagnosis was 2 months or less in 77% patients but never beyond 6 months. (3) 81.8% patients had liver enlargement, 59.1% splenomegaly and 61.4% sternum tenderness. (4) All patients showed marked anemia with an average hemoglobin of 65 g/L. BPC count was less than 100 x 10(9)/L in 76% patients and WBC was more than 10 x 10(9)/L in 77%. (5) Plasma cell number in the marrow was markedly increased with an average of 69%, of which the blast cells and immature forms were predominant. (6) No destruction of bones was shown on X-ray film in 68.3% patients. (7) The response to chemotherapy was poor with a total response rate of 18% and a mean survival of 2 months. All the above-mentioned clinical features were significantly different from those of MM. In addition, these two diseases were also different in cytology, cytogenetics and ultrastructure. Therefore, PPCL should be considered as a special type of acute leukemia distinct from MM. High dose of alkylating agents in combination with autologous bone marrow transplantation might improve the prognosis.

Adolescent↗

Intraoperative determination of thoracic duct injury with 131I-fat. An experimental study on dogs.

The creation of an experimental animal model of traumatic chylothorax was verified by 131I labelled fat (peanut oil). 15 dogs of 3 groups were administered 131I labelled oil via a gastric tube. The results were compared between the two experimental groups and a control group with nonchylous pleural effusion. Dynamic radioactive studies on the blood and pleural fluid showed that the absorption curve of the dog's blood and chyle to 131I labelled oil was identical regardless of different attitudes, and was also similar to that of the human blood because the peak appeared 4 hours after the administration of 131I labelled oil, at which the radioactivity of chyle reached its maximum, more powerful than that of the blood collected at the same time (P less than 0.01). The 99% confidence limitation of radioactivity of the pleural fluid, and the radioactivity ratio of the pleural fluid to blood in the experimental groups were 1.8-10.5 and 493-2340 cpm respectively. The specific characteristics of chyle was then determined qualitatively according to the quantitative norms. We conclude that the technique is parallel with the normal physiological pattern and seems to be more simple and reliable than the conventional methods for detection of intraoperative injury of the thoracic duct and early diagnosis of postoperative chylothorax.

Animals↗

Avoiding anastomotic leakage following esophagogastrostomy.

The most serious complication following esophagectomy and conventional intrathoracic esophagogastrostomy is anastomotic leakage, which contributes to both a high mortality and morbidity postoperatively. The incidence of anastomotic leakage reported in a recent 10 year period ranged from 3% to 18%, with a mean of 4.9%. A series of 433 esophagogastrostomies were performed in our institute from 1954 to 1981 for various esophageal lesions, including 414 cases of carcinoma of the esophagus. A conventional esophagogastrostomy was carried out in 319 patients and 12 leaks occurred postoperatively, an incidence of 3.7%. In comparison, another group of 114 patients underwent "tunnel" esophagogastrostomy, a technique that we designed. There was only one leak, an incidence of 0.87%. The "tunnel" esophagogastrostomy is therefore recommended as a reliable operative procedure for minimizing the incidence of anastomotic leakage. The operative technique is described in detail.

Esophageal Neoplasms↗

An integrative analysis to sleep functions.

Various studies suggest that some sleep functions, especially some slow wave sleep functions, are indispensable in mammals and related to brain regulation. It has been proposed that two of these functions are the adjustment of emotional balance and the processing of acquired emotional memories. During waking, the gradual accumulation of various randomly learned emotional memories in the limbic structures would inevitably imbalance and disorganize emotional behaviors. Although the emotional balance can be restored during waking by the ascending NA, DA, ACh and 5-HT systems, their roles in memory retention and emotional regulation may sometimes be dissociated and their adjustment of the emotional balance can only be a transient effect. On the other hand, the function of slow wave sleep for emotional adjustment can be long-lasting and is in agreement with its function on the processing of emotional memories. As a result, these sleep functions become indispensable in preventing the emotional imbalance inevitably caused by the accumulation of emotional memories. The effects of rapid eye movement sleep on memory and emotional regulation are just opposite to those of slow wave sleep. Low vigilance is required as premise for sleep to accomplish these indispensable functions.

Animals↗