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J Cai

Publications and source records attributed to J Cai.

At least 73 records · Page 4Linked to original sources
PubMed2001

[The level of plasma-soluble Fas and its clinical value in patients with lung carcinoma].

OBJECTIVE: To explore the clinical value of plasma-soluble Fas (Fas) in patients with lung carcinoma. METHODS: Plasma-Fas level was measured by ELISA method. T lymphocyte phenotype was analysed by flow cytometry in 60 patients with lung cancer. RESULTS: The level of Fas was higher in 40% patients. There was no relationship between level of Fas and pathology. But level of Fas was associated with clinical stage, there was higher level of Fas in patients with advanced neoplastic disease than early stage. The frequencies of activated T cells (CD3+, HLA-DR+) and NK cells (CD16+, CD56+) were also significantly increased in advanced neoplastic patients. However, there was a significant decrease in helper T cells (CD4+, CD8-) in advanced patients. Primary diagnosed SCLC patients with elevated Fas often had good responses to chemotherapy. Plasma Fas level decreased to normal through effective therapy. CONCLUSIONS: There is a elevated plasma-Fas level in patients with lung cancer. It is associated with lymphocyte phenotype. Plasma-Fas may be used as a useful parameter in predicting response to therapy or disease activity.

Adult↗
PubMed2001

[Prognosis of patients with primary liver carcinoma treated with local resection].

OBJECTIVE: To discuss the prognosis of primary liver carcinoma treated with local resection and factors affecting prognosis. METHODS: The data on 130 patients who had been treated from October 1989 to October 1995 were reviewed retrospectively. RESULTS: Curative local resection was performed in 130 patients. Death rate of operation was 0.7%, and the incidence of complications 16.1% (n = 18). The overall 1-, 3- and 5-year survival rates were 82.1%, 60.6% ,48.2%, respectively. Involvement of blood vessels or liver capsules as well as the increase of AST before operation are the significant factors affecting prognosis (P < 0.05). CONCLUSIONS: Local resection is a method characterized by little damage, less bleeding, less complication and good prognosis.

Adult↗
PubMed2000

Disulfide bonds of GM2 synthase homodimers. Antiparallel orientation of the catalytic domains.

GM2 synthase is a homodimer in which the subunits are joined by lumenal domain disulfide bond(s). To define the disulfide bond pattern of this enzyme, we analyzed a soluble form by chemical fragmentation, enzymatic digestion, and mass spectrometry and a full-length form by site-directed mutagenesis. All Cys residues of the lumenal domain of GM2 synthase are disulfide bonded with Cys(429) and Cys(476) forming a disulfide-bonded pair while Cys(80) and Cys(82) are disulfide bonded in combination with Cys(412) and Cys(529). Partial reduction to produce monomers converted Cys(80) and Cys(82) to free thiols while the Cys(429) to Cys(476) disulfide remained intact. CNBr cleavage at amino acid 330 produced a monomer-sized band under nonreducing conditions which was converted upon reduction to a 40-kDa fragment and a 24-kDa myc-positive fragment. Double mutation of Cys(80) and Cys(82) to Ser produced monomers but not dimers. In summary these results demonstrate that Cys(429) and Cys(476) form an intrasubunit disulfide while the intersubunit disulfides formed by both Cys(80) and Cys(82) with Cys(412) and Cys(529) are responsible for formation of the homodimer. This disulfide bond arrangement results in an antiparallel orientation of the catalytic domains of the GM2 synthase homodimer.

Amino Acid Sequence↗
PubMed2000

Permutation tests for comparing marginal survival functions with clustered failure time data.

We propose a class of two-sample non-parametric permutation tests to compare the marginal survival distributions of two groups when the failure times are correlated within cluster, with clusters nested within each group. The permutation distribution effectively takes into account the correlation between failure times within a cluster. The method is able to handle data with clusters of either fixed or variable sizes. Moreover, this class of test statistics is sensitive to various alternatives. The size and power of the proposed tests are assessed by a series of simulation studies. The method is illustrated by application to data from the Hypertension Detection and Follow-up program trial.

Adult↗
PubMed2000

Kaposi sarcoma is a therapeutic target for vitamin D(3) receptor agonist.

Kaposi sarcoma (KS) is responsive to a number of different steroid hormones, such as glucocorticoids and retinoids. An active metabolite of vitamin D, 1alpha,25 dihydroxyvitamin D(3), was used to study the effect of this steroid hormone in KS. Steroid hormones exert their effect through their cognate nuclear receptors, which for vitamin D metabolites is the vitamin D receptor (VDR). It was first shown that KS cell lines and primary tumor tissue express high levels of VDR, whereas endothelial cells had minimal expression and fibroblasts had no expression. Second, KS cell growth was inhibited by VDR agonist 1alpha,25 dihydroxyvitamin D(3) with a 50% inhibitory concentration of 5 x 10 -8 mol/L, whereas endothelial cells and fibroblast cells showed no response. Studies on the mechanism of KS tumor growth inhibition by 1alpha,25 dihydroxyvitamin D(3) showed that production of autocrine growth factors interleukin (IL)-6 and IL-8 was reduced in a dose-dependent manner, whereas no effect was observed on vascular endothelial growth factor and basic fibroblast growth factor. Transcription initiated at the IL-6 promoter was repressed by VDR agonist. The DNA sequences required to mediate this repression were localized to nucleotides -225/-110 in the 5'-flanking region. The antitumor activity of VDR agonists was also confirmed in KS tumor xenograft and after topical application in patients with KS. 1alpha,25 Dihydroxyvitamin D(3) and its analogs may thus be candidates for clinical development in KS.

Adult↗
PubMed2000

Metabolism of lipid peroxidation product, 4-hydroxynonenal (HNE) in rat erythrocytes: role of aldose reductase.

Lipid peroxidation represents a significant source of erythrocyte dysfunction and aging. Because the toxicity of lipid peroxidation appears to be in part due to aldehydic end products, we examined, in rat erythrocytes, the metabolism of 4-hydroxy-trans-2-nonenal (HNE), one of the most abundant and toxic lipid-derived aldehydes. Packed erythrocytes, 0.1 ml, completely metabolized 20 nmoles of HNE in 20 min. The glutathione conjugate of HNE and 4-hydroxynonanoic acid (HNA) represented 70 and 25% of the total metabolism, respectively. Approximately 70% of the metabolites were extruded to the medium. Upon electrospray ionization mass spectrometry, the glutathione conjugate resolved into two distinct species corresponding to glutathionyl HNE (GS-HNE) and glutathionyl 1,4-dihydroxynonene (GS-DHN). The concentration of GS-DHN formed was twice that of GS-HNE. Inhibition of aldose reductase by sorbinil and tolrestat led to a selective decrease in the formation of GS-DHN, although the extent of HNE glutathiolation was unaffected. Inhibitors of aldehyde or alcohol dehydrogenase, i.e., cyanamide and 4-methyl pyrazole, had no effect on the formation of HNA and GS-DHN, indicating that these enzymes are not significant participants in the erythrocyte HNE metabolism. Thus, oxidation to HNA, conjugation with glutathione, and further reduction of the conjugate by aldose reductase appear to be the major pathways of HNE metabolism in erythrocytes. These pathways may be critical determinants of erythrocyte toxicity due to lipid peroxidation-derived aldehydes.

Aldehyde Reductase↗
PubMed2000

Activation by nicotine of striatal neurons receiving excitatory input from the substantia nigra via dopamine release.

An electrophysiological study was performed to elucidate the role of nicotinic receptors in the striatal neurons in chloral hydrate-anesthetized rats. The effects of microiontophoretic application of nicotine and other drugs were examined on the caudate nucleus (CN) neurons activated monosynaptically by stimulation of the substantia nigra pars compacta (SN). Application of nicotine facilitated spontaneous firing. The nicotine-induced firing of the CN neurons was inhibited by concomitant application of domperidone or hexamethonium. These findings suggested that nicotine enhances dopamine release from the SN-derived dopaminergic nerve terminals by activating the neurons via D2 receptors.

Action Potentials↗
PubMed2000

Two functionally distinct forms of NKX2.1 protein are expressed in the pulmonary epithelium.

The homeodomain transcriptional factor NKX2.1 is critical for normal morphogenesis of the lung, thyroid, and the brain. In the lung, NKX2. 1 binds to and activates the expression of pulmonary differentiation-specific genes SP-A, SP-B, and SP-C. The Nkx2.1 gene is comprised of three exons separated by two introns. In both thyroid and lung, the predominant Nkx2.1 transcript includes exons II and III and is translated into a 371 amino acid protein. A minor transcript also exists which includes all three exons. This transcript encodes a 401 amino acid isoform of NKX2.1. The 30 amino acid extension is highly conserved amongst various mammalian species. In the current study, we demonstrate that the two NKX2.1 isoforms are functionally distinct and their corresponding transcripts are expressed differentially during mouse embryonic lung development. The results demonstrate that the longer isoform of NKX2.1 exhibits reduced activity in transactivating an SP-C target promoter when compared to the truncated major NKX2.1 protein. Site directed mutagenesis of the 30 amino acid peptide extension suggests that this fragment alters the activity of 5E likely by steric interference.

Amino Acid Sequence↗
PubMed2000

Prevention of acute liver failure in rats with reversibly immortalized human hepatocytes.

Because of a critical shortage in suitable organs, many patients with terminal liver disease die each year before liver transplantation can be performed. Transplantation of isolated hepatocytes has been proposed for the temporary metabolic support of patients awaiting liver transplantation or spontaneous reversion of their liver disease. A major limitation of this form of therapy is the present inability to isolate an adequate number of transplantable hepatocytes. A highly differentiated cell line, NKNT-3, was generated by retroviral transfer in normal primary adult human hepatocytes of an immortalizing gene that can be subsequently and completely excised by Cre/Lox site-specific recombination. When transplanted into the spleen of rats under transient immunosuppression, reversibly immortalized NKNT-3 cells provided life-saving metabolic support during acute liver failure induced by 90% hepatectomy.

Adult↗
PubMed2000

Redox state of glutathione in human plasma.

Thiol and disulfide forms of glutathione (GSH) and cysteine (Cys) were measured in plasma from 24 healthy individuals aged 25-35 and redox potential values (E(h)) for thiol/disulfide couples were calculated using the Nernst equation. Although the concentration of GSH (2.8 +/- 0.9 microM) was much greater than that of GSSG (0.14 +/- 0.04 microM), the redox potential of the GSSG/2GSH pool (-137 +/- 9 mV) was considerably more oxidized than values for tissues and cultured cells (-185 to -258 mV). This indicates that a rapid oxidation of GSH occurs upon release into plasma. The difference in values between individuals was remarkably small, suggesting that the rates of reduction and oxidation in the plasma are closely balanced to maintain this redox potential. The redox potential for the Cys and cystine (CySS) pool (-80 +/- 9 mV) was 57 mV more oxidized, showing that the GSSG/2GSH and the CySS/2Cys pools are not in redox equilibrium in the plasma. Potentials for thiol/disulfide couples involving CysGly were intermediate between the values for these couples. Regression analyses showed that the redox potentials for the different thiol/disulfide couples within individuals were correlated, with the E(h) for CySS-mono-Gly/(Cys. CysGly) providing the best correlation with other low molecular weight pools as well as protein disulfides of GSH, CysGly and Cys. These results suggest that E(h) values for GSSG/2GSH and CySS-mono-Gly/(Cys. CysGly) may provide useful means to quantitatively express the oxidant/antioxidant balance in clinical and epidemiologic studies.

Adult↗
PubMed2000

Nuclear profiles of cancer cells reveal the metastatic potential of gastric cancer.

Nuclear profiles have been reported as useful prognostic predictors in various cancers. Data from computerized morphometry are objective and can be quickly derived using conventional microscopic analysis, but image analysis of nuclear features has only rarely been applied to investigations of gastric cancer. The aim of this study was to evaluate the correlation between one of these morphological nuclear features and the clinicopathological parameters in patients with gastric cancer. The morphometric nuclear feature (nuclear area) was analysed in 400 patients with gastric cancer. In each case, 300 cancer nuclei on routine haematoxylin and eosin-stained slides were analysed through the use of a computer-assisted image analysis system which traced the nuclear profiles (magnificationx400) on a computer monitor. The morphometric data were compared with the patients' clinicopathological status and survival rate. The mean nuclear area (NA) of cancer cells from 400 cases of gastric cancer was 47.2 microm(2). The NAs of cancer cells from tumours with microvessel invasion (lymphatic or venous invasion), lymph node metastasis or hepatic metastasis at the time of operation were significantly larger than those of cancer cells from tumours without such invasion or metastases. Cytokeratin (CK) immunostaining was performed on 2577 lymph nodes from 91 patients with advanced gastric cancer (pT3, pN0, pM0, stage II) to detect micrometastases. CK-positive lymph nodes were detected in 350 of 2577 lymph nodes (13. 6%) and in 62 of 91 patients (68.1%). The mean NA of cancer cells from 62 tumours with micrometastases (44 microm(2)) was larger than that of cancer cells from 29 tumours without micrometastases (38.8 microm(2), p=0.043), and a significant positive correlation was detected between the NAs of cancer cells from 91 tumours and the number of micrometastatic lymph nodes of 91 patients (rho=0.278, p=0. 008). Cancer cells with large NA correlated strongly with haematogenous and lymph node recurrence or relapse after gastrectomy and the NA of cancer cells was identified as an independent prognostic factor in gastric cancer. Nuclear morphometry is an objective, reproducible, and technically uncomplicated procedure. The NA of cancer cells correlates closely with the metastatic potential of gastric cancer. Nuclear morphometry may therefore be useful for the selection of patients who are at risk of haematogenous or lymph node metastatic recurrence after surgery.

Adenocarcinoma↗
PubMed2000

Case-cohort analysis of brain cancer and leukemia in electric utility workers using a refined magnetic field job-exposure matrix.

BACKGROUND: The potential association between occupational electric and magnetic field exposure and cancer is well documented in the literature, but there is uncertainty regarding a causal relation. METHODS: Using data from a completed cohort study, we sought to refine the job-exposure matrix in a case-cohort analysis by regrouping jobs into more homogeneous groups, but without making additional measurements. From the original cohort, we selected the 164 men who died of leukemia, 145 men who died of brain cancer, and a random subcohort of 800 men (0.6% of the cohort). Erroneous job assignments were corrected and job groups were subdivided based on differences in work environments or tasks performed. RESULTS: Magnetic field exposure remained unrelated to leukemia mortality and positively associated with brain cancer mortality based on both cumulative and average magnetic field indices. Although not monotonic across the middle intervals, increased risk of brain cancer was found in relation to career exposure, with risk ratios of 1.8 (95% CI = 0.7-4.7) and 2.5 (95% CI = 1.0-6.3) in the uppermost categories for cumulative and average exposure, stronger for exposure 2-10 years past. CONCLUSIONS: Improvements in exposure assignment based only on reassignment of job titles to occupational categories had little impact on the measured associations of magnetic fields with leukemia or brain cancer.

Brain Neoplasms↗
PubMed2000

Evidence for the differential regulation of Nkx-6.1 expression in the ventral spinal cord and foregut by Shh-dependent and -independent mechanisms.

The Nkx-6.1 homeodomain transcription factor was previously shown to be expressed in ventral neural progenitor cells and subsequently subsets of unidentified motor neurons during early neural development. In this study, we identify a specific subpopulation of motor neurons, the median half of the lateral motor neuron column (LMCm), that retain a strong expression of Nkx-6.1. In addition, we report novel patterns of Nkx-6.1 expression in several mesenchymal tissues surrounding Sonic hedgehog (Shh)-expressing cells, including ventral spinal meninges, esophageal mesenchyme, and dorsal tracheal mesenchyme. Whereas Shh signaling is required for Nkx-6.1 expression in the ventral neural tube and spinal meninges, an Shh-independent pathway appears to operate in regulating Nkx-6.1 expression in the foregut. The persistent and robust expression of Nkx-6.1 in motor neurons and mesenchymal cells suggests an important role for Nkx-6.1 in controlling cell fate specification and differentiation. genesis 27:6-11, 2000.

Animals↗
PubMed2000

Selective expression of Nkx-2.2 transcription factor in chicken oligodendrocyte progenitors and implications for the embryonic origin of oligodendrocytes.

Recent studies have demonstrated that oligodendrocytes originate from the ventral region of the developing spinal cord. However, the precise neuroepithelial origin of oligodendrocytes remains controversial, and the transcriptional control of oligodendrocyte lineage specification is largely unknown. Here we present evidence that oligodendrocytes in the embryonic chicken spinal cord can be generated from neuroepithelial cells that express the Nkx-2.2 homeodomain transcription factor. Nkx-2.2 expression is initially confined to a narrow stripe of neuroepithelium flanking the floor plate. Later, Nkx-2.2+ cells migrate ventrally and dorsolaterally into the surrounding gray and white matter regions where they undergo rapid proliferation. Double labeling experiments revealed that Nkx-2.2+ cells coexpress markers specific for oligodendrocyte progenitors, e.g., PDGFRalpha+, O4, and R-mAb antigens. In the brain, the Nkx-2.2 cells are also highly migratory and can generate oligodendrocytes. The persistent expression of the Nkx-2.2 homeodomain transcription factor in the oligodendrocyte lineage suggests its important role in the control of oligodendrocyte development.

Animals↗
PubMed2000

Construction of a non-tumorigenic rat hepatocyte cell line for transplantation: reversal of hepatocyte immortalization by site-specific excision of the SV40 T antigen.

BACKGROUND/AIMS: Hepatocytes immortalized with a temperature-sensitive SV40 large T antigen (SV40Tag) function as well as primary hepatocytes following transplantation to reverse hepatic encephalopathy and improve survival in rodents with liver failure. The continued presence of SV40Tag in the conditionally immortalized hepatocytes may increase the risk of malignant tumor growth in transplant recipients. METHODS: We immortalized hepatocytes using a recombinant retrovirus containing the gene encoding SV40Tag flanked by loxP recombination target sites. Excision of SV40Tag from immortalized cells could then be accomplished by site-specific recombination with Cre-recombinase. RESULTS: Cells immortalized with this recombinant virus expressed SV40Tag and doubled in number every 48 h. After excision of the gene encoding SV40Tag with Cre-recombinase, cells stopped growing, DNA synthesis fell by 90%, and production of liver-specific mRNAs was either increased or became newly detectable. In addition, the morphology and epithelial cell polarity of the cells became more characteristic of differentiated hepatocytes. To determine their malignant potential, immortalized hepatocytes were transfected to express a second oncogene, activated H-ras. SV40Tag+/H-ras+-immortalized cells were capable of anchorage-independent growth and developed into tumors when injected in severe combined immunodeficiency mice. While Cre-recombinase delivery by recombinant adenovirus infection was not 100% efficient, when SV40Tag excision occurred anchorage-independent growth stopped and tumor formation in immunodeficient mice was abolished. Immortalized hepatocytes also contained the gene encoding herpes simplex virus thymidine kinase and treatment with ganciclovir produced complete regression of established tumors in mice. CONCLUSIONS: These studies extend previous work that indicates that a transplantable hepatocyte cell line could be developed for clinical use.

Animals↗
PubMed2000

Effects of three different Ca(2+) pump ATPase inhibitors on evoked contractions in rabbit aorta and activities of Ca(2+) pump ATPases in porcine aorta.

Using vascular smooth muscle, we describe the actions of three pharmacological tools, cyclopiazonic acid (CPA), thapsigargin (TG) and 2,5-di-(tert-butyl)-1,4-benzohydroquinone (tBHQ), which are presumed to act as selective inhibitors of the sarco-endoplasmic reticulum Ca(2+)-ATPases (SERCAs). In porcine aortic smooth muscle microsomes two Ca(2+)-ATPase activities have been described, one vanadate-sensitive and one vanadate-resistant, representing the Ca(2+)-ATPase activities of the plasma membrane and SERCAs, respectively. In agreement, CPA, TG and tBHQ, in the concentration range 0.1 microM to 0.1 mM, dose-dependently inhibit the Ca(2+)-ATPase activity only in the vanadate-resistant microsomes. However, 0.1 mM tBHQ also significantly inhibited the Ca(2+)-ATPase activity of vanadate-sensitive microsomes. In rabbit aortic rings, all three SERCA inhibitors produced a dose-dependant inhibition of contractions evoked by 20 mM caffeine or 1 microM phenylephrine (PE) in a Ca(2+)-free physiological solution. However, in PE-contracted rings, tBHQ (> or =30 microM) also significantly inhibited the ability of cromakalim to induce relaxation. In conclusion, the data suggest that CPA, TG and tBHQ can all act as selective SERCA inhibitors in both porcine and rabbit aortic smooth muscle. However, in contrast to CPA and TG, high concentrations of tBHQ can exhibit some nonspecific effects, which include inhibition of the plasma membrane Ca(2+)-ATPase and possibly K(+) channels regulated by cromakalim.

Animals↗