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Biomedical subjects

Z Fan

Publications and source records attributed to Z Fan.

At least 127 records · Page 7Linked to original sources
PubMed1997

Reciprocal changes in p27(Kip1) and p21(Cip1) in growth inhibition mediated by blockade or overstimulation of epidermal growth factor receptors.

Many human epithelial tumors express high levels of epidermal growth factor (EGF) receptors. A human-mouse chimeric version of anti-EGF receptor monoclonal antibody (mAb) C225, which blocks receptor activation and produces inhibition of cell proliferation, is currently being investigated in clinical trials. When cells bear high numbers of EGF receptors, either complete blockade of receptors with mAb 225 or full activation of receptors with EGF results in inhibition of proliferation. In the present study, we have explored the molecular mechanisms explaining how a receptor inhibitor, mAb 225, and a receptor activator, EGF, can both produce growth inhibition of A431 human squamous epithelial carcinoma cells. We reported previously that inhibition of A431 cells by EGF is associated with up-regulation of p21(Cip1). We now demonstrate that mAb 255-mediated inhibition is associated with up-regulation of p27(Kip1), which binds to and inactivates cyclin-dependent kinase-2 activity and produces cell cycle arrest in G1. Furthermore, inhibition by mAb 225 can be overcome by titrating the cultures with increasing concentrations of EGF, which is accompanied by a concurrent fall in the level of p27(Kip1). At properly titrated concentrations of mAb 225 and EGF, the inhibitory activities of both mAb 225 and EGF are counterbalanced and abolished. When EGF concentrations reach levels high enough to compete with mAb to produce near-saturating levels of receptor activation, p27(Kip1) falls below basal levels; however, the concomitant marked rise in the level of p21(Cip1) results in growth inhibition. Our data suggest that although p27(Kip1) and p21(Cip1) are induced and act independently, they play reciprocal roles in mediating inhibition of A431 cell growth by blockade of EGF receptors with mAb 225 and by activation of receptors with saturating concentrations of EGF.

Animals↗
PubMed1996

Two human paramyotonia congenita mutations have opposite effects on lidocaine block of Na+ channels expressed in a mammalian cell line.

1. Two mutant human skeletal muscle voltage-gated Na+ channel alpha-subunits (hSkM1), with mutations found in patients with hereditary paramyotonia congenita (T1313M on the III-IV linker and R1448C on the outside of S4 of repeat IV), and wild-type hSkM1 channels were expressed in a human embryonic kidney cell lines (tsA201) using recombinant cDNA. 2. Compared with wild-type, both mutants exhibited altered inactivation phenotypes. Current decay was slowed for both, but voltage-dependent availability from inactivation was shifted in the negative direction for R1448C and in the positive direction for T1313M. 3. The hypothesis that a local anaesthetic, lidocaine (lignocaine), binds primarily to the inactivated state to block the channel was reassessed by testing lidocaine block of these two mutants and the wild-type channel. 4. T1313M showed reduced phasic block, but R1448C showed increased phasic block for trains of depolarizations. 5. Rest block (from -120 mV) was increased for R1448C (IC50 approximately equal to 0.2 mM) and decreased for T1313M (IC50 approximately equal to 1.3 mM) compared with wild-type (IC50 approximately 0.5 mM), but these differences were diminished at a holding potential of -150 mV, suggesting that the differences were caused by binding to the inactivated state rather than a different affinity of lidocaine for the resting state. 6. Inactivated state affinity measured from lidocaine-induced shifts in voltage-dependent availability was reduced for T1313M (Kd = 63 microM) but little changed for R1448C (Kd = 14 microM) compared with wild-type (Kd = 11 microM). Two pulse recovery protocols showed faster recovery from lidocaine block for T1313M and slower recovery for R1448C. Together these accounted for the opposite effects on lidocaine phasic block observed for the mutant channels. 7. Neither mutation is located at a putative lidocaine binding site in domain 4 S6, yet both affected lidocaine block. The data suggest that R1448C altered phasic lidocaine block mainly through altered kinetics, but T1313M altered block through a change in affinity for the inactivated state. These findings have implications for drug therapy of paramyotonia congenita, and also provide an insight into structural requirements for drug affinity.

Anesthetics, Local↗
PubMed1996

Anti-epidermal growth factor receptor monoclonal antibody 225 up-regulates p27KIP1 and induces G1 arrest in prostatic cancer cell line DU145.

Autocrine production of transforming growth factor alpha and overexpression of the epidermal growth factor receptor (EGFR) may contribute to androgen-independent prostatic cancer growth at both primary and metastatic sites. Previously, we showed that human EGFR-blocking monoclonal antibody mAb225 inhibited the growth of DU145 human prostatic cancer cells. Here we explore the hypothesis that mAb225 may act by interfering with cell cycle traversal in these cells. Treatment with mAb225 induced G1 arrest, which was accompanied by a marked decrease in CDK2-, cyclin A-, and cyclin E-associated histone H1 kinase activities, and a sustained increase in cell cycle inhibitor p27KIP1. The increased p27KIP1 levels were attributable to elevation of both transcription and translation. CDK2 associated with p27KIP1 was increased in mAb225-treated DU145 cells. The retinoblastoma-related protein p130 remained hypophosphorylated in these retinoblastoma-negative cells. These studies demonstrate that the antiproliferative effect of EGFR blockade in DU145 cells may be mediated by up-regulation of p27KIP1 at both the mRNA and protein levels.

Antibodies, Monoclonal↗
PubMed1996

Involvement of p27KIP1 in G1 arrest mediated by an anti-epidermal growth factor receptor monoclonal antibody.

Activation of the cyclin dependent kinases (CDK4/CDK6 and CDK2) is required for G1 phase progression and entry into S-phase. The activation of these kinases is regulated by checkpoints that monitor environmental and intracellular conditions. Progression into S-phase is controlled, in part, by the availability of growth factors, and we have investigated the relationship between growth factor availability and the activation of the CDK kinases. Blocking activation of epidermal growth factor (EGF) receptor tyrosine kinase with anti-EGF receptor monoclonal antibody (mAb) 225 induces G1 phase cell cycle arrest in DiFi human colon adenocarcinoma cells. When DiFi cells are treated with mAb 225 for 24 h, we observe marked decreases in the activities of CDK2 kinase and cyclin E-associated CDK kinase which are not accompanied by reduced levels of cyclin E and CDK2 proteins. However, the amount of cyclin/CDK kinase inhibitor p27KIP1 increases in the mAb-treated cells and p27KIP1 is bound to CDK2 in increasing amounts. Immunodepletion of p27KIP1 removes an inhibitory activity from lysates of mAb-treated cells: the immunodepleted and heated lysates lose the capacity to inhibit cyclin E/CDK2 activity in an in vitro assay. The results suggest that G1 arrest in the cell cycle induced by EGF receptor blockade involves p27KIP1.

Antibodies, Monoclonal↗
PubMed1996

Rat inwardly rectifying potassium channel Kir6.2: cloning electrophysiological characterization, and decreased expression in pancreatic islets of male Zucker diabetic fatty rats.

The ATP-sensitive potassium channel of insulin-secreting pancreatic beta-cells is a complex of Kir6.2, a member of the inwardly rectifying potassium channel superfamily, and the sulfonylurea receptor. We have isolated cDNA clones encoding rat Kir6.2. Co-expression of rat Kir6.2 and sulfonylurea receptor in human embryonic kidney cells generated a potassium current with the properties of the beta-cell ATP-sensitive potassium channel. A quantitative reverse transcriptase-polymerase chain reaction assay indicated that Kir6.2 and sulfonylurea receptor mRNAs were abundantly expressed in rat islets and that expression of Kir6.2 mRNA was reduced by >70% in islets from Zucker diabetic fatty male rats, whereas there was no significant change in sulfonylurea receptor mRNA levels. Thus, decreased expression of Kir6.2 could contribute to the beta-cell dysfunction which characterizes diabetes mellitus in this animal model.

Adenosine Triphosphate↗
PubMed1996

Intraoperative use of mitomycin in trabeculectomy.

Mitomycin (0.2 mg/ml) was applied intraoperatively to 26 glaucomatous patients (33 eyes) during conventional trabeculectomy procedure. Most of them were considered to be at high risk of surgical failure. The conjunctival flap was fornix-based in 9 patients (11 eyes). The success rate was 84.8% without any serious side effect.

Female↗
PubMed1996

Variation in the genome of rice tungro bacilliform virus: molecular characterization of six isolates.

The DNA genomes of isolates of rice tungro bacilliform virus from Bangladesh, India, Indonesia, Malaysia and Thailand were cloned and compared with that of the type isolate from the Philippines. Restriction endonuclease maps revealed differences between the isolates and cross-hybridization showed that they fell into two groups, those from the Indian subcontinent and those from south-east Asian countries. The genomes of isolates from the Indian subcontinent contained a deletion of 64 bp when compared with those from south-east Asia. The implications of this variation are discussed.

Base Sequence↗
PubMed1996

Coexpression of beta 1 with cardiac sodium channel alpha subunits in oocytes decreases lidocaine block.

Coexpression of the rat beta 1 subunit with rat brain and skeletal muscle sodium channel alpha subunits in Xenopus oocytes normalizes currents by accelerating sodium current decay kinetics, shifting steady state availability relationships, and accelerating recovery from inactivation. Unlike brain and skeletal muscle, the heart alpha subunit expressed without beta 1 has native-like decay kinetics in oocytes. Messenger RNA for beta 1 has been found in heart, but whether and how it affects cardiac sodium channel function are unclear. We studied coexpression of human heart alpha subunit with beta 1 in Xenopus oocytes using two microelectrode voltage-clamp and macropatch techniques. Coexpression with beta 1 caused a significant positive shift of 3-7 mV in the midpoint of the steady state inactivation relationship but did not affect single-channel conductance, activation, current decay, or recovery from inactivation. Sensitivity to lidocaine block, however, was decreased for both resting state block (Kd = 0.5-1.3 mM) and phasic block in response to pulse trains, but inactivated state block was not affected (Kd = approximately 10 microM). Coexpression with beta 1 increased the rate of recovery from lidocaine block, which accounted for the major part of the observed differences in tonic and phasic block. A beta 1 construct with the cytoplasmic tail removed also produced these effects, demonstrating that the beta 1 cytoplasmic tail was not involved in altering lidocaine block. We conclude that the beta 1 subunit is capable of affecting function of the cardiac sodium channel in oocytes by decreasing tonic and phasic lidocaine block with small effects on gating.

Animals↗
PubMed1996

[Relationship between cellular DNA and expression of epidermal growth factor receptor in pleomorphic adenoma of lacrimal gland].

OBJECTIVE: To obtain the information about whether expression of epidermal growth factor (EGF) receptor is related to the proliferative activity of tumor. METHODS: The expression of EGF receptor and DNA content of pleomorphic adenoma of lacrimal gland in 32 cases were detected by an immunohistochemical avidin biotin peroxidase complex method and determined by an image analysis technique, respectively. The relationship between the expression of EGF receptor and DNA content was analyzed. RESULTS: 10 tumors were stained positively with anti-EGF receptor antibody, the DNA contents of 14 cases were increased, their DNA ploidy distribution pattern showed two or several peaks. Good correlation has been found between the expression of EGF receptor and DNA ploidy distribution pattern, and the DNA distribution pattern of tumor with positive EGF receptor expression showed mainly two or several peaks (P < 0.01). CONCLUSION: The expression of EGF receptor of pleomorphic tumor of lacrimal gland is related to the proliferative activity of tumor cells.

Adenoma, Pleomorphic↗
PubMed1996

[Relationship between heart rate variability and clinical features and prognosis of acute myocardial infarction].

Heart rate variability (HRV) was studied prospectively in 118 consecutive patients with acute myocardial infarction (AMI). HRV in AMI patients was significantly lower than that in normal controls, both at the 19th hour and the end of the 3rd week after the onset of AMI. Moreover, HRV at the end of 3rd week HRV in patients with cardiac death was also lower than that in the survivals. Measurements of ultra-low frequency power, total frequency power, very low frequency power, and the average of the standard deviation of every 5-minute period were independent predictors of cardiac death. All these 4 measurements have highly significant correlation (P < 0.01) and are better predictors of prognosis than other clinical variables. It is revealed that HRV at the end of 3rd week after the onset of AMI has much greater prognostic value than that at the initial period.

Adult↗
PubMed1996

[Clinical applications of China-made saline-filled breast implants--a report of 62 cases].

To evaluate the China-made saline-filled breast implants, we observed 62 patients (123 sides of breasts) who received augmentation mammaplasty from March 1994 to May 1995. The implants of 200 to 450 ml were manufactured in Shanghai. All the implants were placed beneath the pectoralis major muscle and a transient over-inflation was used. Fifty-nine patients had satisfactory results. One case developed breast shrinking postoperatively due to possible damage to the implant. Another two cases were not quite satisfactory because of associated breast ptosis. Thirty-two cases were followed up for 3 months and demonstrated nice-looking and soft breasts. We conclude that (1) the quality of the China-made saline-filled breast implant is good. And (2) transient over-inflation of the implant during the operation is advantageous and is worth recommending.

Adult↗
PubMed1996

[A cohort study on the relationship between standardized mortality of pulmonary heart disease and smoking].

We explored the relationship between the standardized mortality of pulmonary heart disease (PHD) and smoking at Shifang county through a five-year follow-up study of 29,498 farmers over 35 years old. The death ratio of PHD was 30.35%, which stood first in all causes of death. The mortality of PHD for cigar/cigarette smokers regardless of sex was not significantly different from that for nonsmokers (P > 0.05). The RR was 1 or so. The analysis of data stratified by age showed that the specific mortality increased with age in spite of some inequalities smoking; the RR of PHD for cigar/cigarette smokers in all age groups were 1 or so revealing no significant differences (P > 0.05). However, the standardized mortality of PHD increased with the accumulated amount of smoking. The relationship between the mortality of PHD and short-term smoking with small dose was not significant (P > 0.05), but when the accumulated amount reached certain level, i.e. the smoker consumed cigar more than 270 kg or consumed cigarette more than 20,000 packs, the relationship between the behavior of cigar/cigarette smoking and the mortality of PHD became apparent. The RRs were 1.40-3.94 and the ARs 171-1610 per 100,000 person years (P < 0.05-0.01).

Adult↗
PubMed1996

[Relationship between expression of P21ras and cellular DNA in pleomorphic adenoma of lacrimal gland].

BACKGROUND: The pleomorphic adenoma is the most frequent tumor of the human lacrimal gland comprising about 50% of the epithelial tumors of this organ. Although being benign, local recurrences can occur when the first removal was incomplete and malignant transformation is also not in frequent. It is well known that many sorts of cellular oncogene products are involved in the initiation, promotion and progression of the human neoplasm. Our purpose was to know whether there is abnormal expression of P21ras in pleomorphic adenoma. METHODS: We have undertaken a study of the expression of P21ras in 5 normal tissues and 32 pleomorphic adenoma of lacrimal gland by immunohistochemical means using the monoclone antibody F-132-62 and the nuclear DNA content in the tumor was assayed by image analysis technique. RESULTS: Normal tissues of lacrimal gland were negative, 12 tumors were stained positively with the antibody. The DNA content of 14 cases of tumor was increased. Their DNA ploidy distribution pattern showed two or several peaks. Good correlation has been found between the expression of P21ras and DNA ploidy distribution pattern, the DNA ploidy distribution pattern of tumor which expressed p21ras showed mainly two or several peaks. P< 0.05. CONCLUSIONS: The result of our studies may suggest that there are increased expression of p21ras in pleomorphic adenoma and the expression of p21ras is related to the promotion and progression of pleomorphic adenoma of lacrimal gland.

Adenoma, Pleomorphic↗
PubMed1996

[Further comment on surgical approach for hemifacial spasm].

A new surgical approach for the treatment of hemifacial spasm was carried out in 110 cases from 1991-1994. The novelty of this new procedure lies in splitting of facial nerve by making multiple cuts along the long axis of the nerve--descriptively a type of "combing". Among these cases, arachnoid thickening and adhesion occurred in 35 cases throughout the vascular course, 66 cases showed vascular compression (60%). A segment of vessel could be seen lying between VII and VIII cranial nerves in 16 cases. Under the latter circumstance steps taken for decompression would be either too risky or impossible. Postoperatively all cases got marked improvement or total disappearance of symptoms & signs. Follow up varying 1-4 years showed recurrence of symptoms in 6 cases (5.4%). This was explaned in light of insufficient splitting. It might be due to lack of experience or on account of vascular enclosures. It was suggested that at least 20 cuts should be made and tested with a minimum of 10mA electric stimulation to achieve good result.

Adult↗