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Biomedical subjects

Z Fan

Publications and source records attributed to Z Fan.

At least 163 records · Page 9Linked to original sources
PubMed1994

The autocrine regulatory effect of vasoactive intestinal peptide on the growth of human pancreatic carcinoma cells.

In the present study, the effects of VIP on the growth of two human pancreatic carcinoma cell lines PU-PAN-1 and PANC-1 were determined using tritiated thymidine incorporation. VIP receptors, intracellular cAMP and polyamines were investigated. The results indicated that VIP at a concentration of 10(-8) mol/L to 10(-7) mol/L can significantly stimulate the growth of PU-PAN-1 cells but not PANC-1 cells. This effect is dose-dependent and abolished by VIP receptor antagonist, [4-C1-Phe6, Leu17] VIP, suggesting VIP receptors in PU-PAN-1 cells may mediate this effect. VIP can markedly elevate the levels of intracellular cAMP and polyamines in PU-PAN-1 cells, indicating that the growth-promoting effect stimulated by VIP may be via a rapid increase in the biosyntheses of cAMP and polyamines. In addition, the VIP-antibody inhibited the growth of PU-PAN-1 cells in serum-free culture medium. The results above suggested that VIP has an autocrine regulatory effect on this pancreatic carcinoma cell line (PU-PAN-1).

Biogenic Polyamines↗
PubMed1994

[Delayed cerebrovascular accident following microvascular decompression of hemifacial spasm].

Two cases of hemifacial spasm received microvascular decompression. Both of them had histories of hypertension and coronary insufficiency. The two cases died on the 12th postoperative day because of cerebrovascular accident. We think that the death was associated with the poor facilities, insufficient skills and lack of close supervision. Also, frequent visits by the families and early activities of the patients may contribute to the accident.

Cerebrovascular Disorders↗
PubMed1994

[Study on pathogenic mechanism of hemifacial spasm].

In 17 cats, areas of focal injury were induced in the facial nerve root near the brain stem by implantation of V-clamp and catgut suture. The electrophysiological examinations were made at 3 weeks after the surgery. When the mandibular branch of the facial nerve was electrically stimulated, a combined activity potential and a delayed activity could be recorded from the orbicular ocular branch of the facial nerve. The delayed activity disappeared after the motornucleu of the facial nerve was blocked with injection of 2% Lidocaine(1.5 microliter). These phenomena suggests that the artifacial synapses have been formed among the demyelinating facial nerve. The antidromic impulse of the mandibular branch of the facial nerve spread to adjacent fibers through the artifacial synapses in REZ of the facial nerve and causes the synkinases and spasm. Delayed activity may be caused by neurons of the motornucleu. Experimental lesion was also examined histologically at 3 weeks following implantation. Injured nerve showed areas of demyelination and Waller's degeneration of adjacent axons. The Nissle substances at the neurons of the motornucleu were dissolved and disappeared.

Action Potentials↗
PubMed1994

[A cohort study on the relationship between the mortality of cerebro-vascular diseases and farmer smokers].

The relationship between the mortality of cerebro-vascular diseases and farmer smokers in Shifang County was studied. The results indicated that the mortality of cerebro-vascular diseases in the male groups of cigarette-smokers older than 65 and cigar-smokers older than 55 was significantly higher than that of the nonsmokers (P < 0.05), the RR being 1.68-3.22. Also, the mortality in the female groups of cigarette-smokers older than 55 and cigar-smokers older than 65 was significantly higher than that of the non-smokers (P < 0.05), the RR being 1.99-3.19. The sex-specific mortalities of the other age groups revealed no significant differences in spite of some inequalities in smoking (P < 0.05). Age should be one of the risk factors for the death of cerebro-vascular diseases regardless of the sex. The mortality rose with the increasing accumulated amount of smoking. The relationship was not significant between the mortality of cerebro-vascular diseases and short-term smokers with small dose (P > 0.05). However, when the accumulated amount reached certain degree, i.e. the smoker consumed cigar more than 270 kg or consumed cigarette more than 10,000 packs, the relationship between the behavior of cigar-smoking and cigarette-smoking and the mortality became apparent, the RR being 2.53-3.91 (P < 0.01).

Adult↗
PubMed1994

Comparison of standard locked-ward treatment versus open-ward rehabilitation treatment for chronic schizophrenic patients. A one-year controlled trial in Canton.

A priority for psychiatric rehabilitation workers in China is to develop less-restrictive methods for managing the estimated 2500 chronically institutionalised patients who are symptomatically stable and have adequate psychosocial functioning but have no family members who are able or willing to take them home. We transferred 45 chronic schizophrenic male in-patients to an open-door rehabilitation ward where they were given as much freedom as possible and encouraged to take part in occupational, social, and recreational activities. The Nurses Observation Scale for Inpatient Evaluation (NOSIE) was used to compare the psychosocial functioning of the 43 patients who completed the year-long trial with that of 43 similar patients who received standard in-patient treatment on a locked ward. Over the year, the experimental group showed a significant improvement in overall functioning, whereas the control group showed no improvement. These findings suggest that open-door rehabilitation wards situated within the hospital can mobilise latent psychosocial functioning and may be a good method for re-introducing chronic schizophrenic patients in China back into the community.

Activities of Daily Living↗
PubMed1994

[Chemiluminescent immunoassay for anti-granulocyte antibody IgG].

In this paper is reported solid phase competitive chemiluminescent immunoassay (CLIA) for anti-granulocyte antibody (AGAb) IgG with N-(4-amiobytul)-N-ethylisoluminol (ABEI) labelled rabbit antibody IgG against granulocyte competing with the analyte and ABEI-CoCl2-H2O2 as the chemiluminescent system. The absolute limit of detection was 3.0 x 10(-14) mol ABEI/tube. One hundred and thirty one individuals were divided into three groups: leukocytopenic group (n = 58), control group (n = 41) and normal group (n = 32). Chemiluminescent index (CLI) was used as the diagnostic criterion for AGAb in serum. The results showed that the positive rate of the leukocytopenic group was significantly higher than that of the control group (P < 0.005), and the sensitivity, specificity and accuracy of the method were 43.1%, 90.2% and 62.6%, respectively.

Granulocytes↗
PubMed1994

[Experimental study of changes in biomechanical properties of pig skin after rapid expansion].

The purpose is to evaluate the biomechanical properties of conventional skin expansion, rapid expansion and unexpanded skin. In four pigs, 240 ml expanders of square shape are placed. The flaps are divided into three groups: (1) Rapid expansion flap: the expander is inflated daily until maximum volume is obtained. (2) Conventional expansion flap: inflation is done weekly. (3) Unexpanded skin is used as control. By using the tensometer, the skin is evaluated for stress strain, stress relaxation, density of strain energy, parameters of strength, and a mathematical model is obtained. We conclude that the biomechanical properties of the expanded skin are different from that of the unexpanded skin. But the biomechanical properties of conventional expanded skin are similar to that of rapid expanded skin. It is shown that the rapid expansion may be accepted in the practice.

Animals↗
PubMed1993

Regulation of epidermal growth factor receptor in NIH3T3/HER14 cells by antireceptor monoclonal antibodies.

The mechanism(s) by which monoclonal antibodies (mAbs) against the epidermal growth factor (EGF) receptor regulate receptor function have been investigated with NIH3T3/HER14 fibroblasts expressing human EGF receptors. Bivalent 225 mAb or monovalent 225 Fab' inhibited transforming growth factor (TGF)-alpha-induced EGF receptor tyrosine phosphorylation and cell proliferation. Culture of HER14 cells with 225 mAb or 225 Fab' did not activate EGF receptor tyrosine kinase when assayed after lysis of cells in SDS sample buffer. However, when cells were cultured with bivalent 225 mAb, but not with monovalent 225 Fab', and were subsequently lysed and further incubated in Triton X-100 lysis buffer containing proteinase and phosphatase inhibitors, receptor phosphorylation was observed. Phosphorylation was confined to tyrosine residues and was inhibited by addition of genistein after lysis, indicating that it was due to the activation of protein tyrosine kinase. The activity of bivalent 225 mAb was unphysiologic, in contrast with TGF-alpha, in that receptor kinase activation occurred only after cell lysis and with delayed kinetics; serine and threonine phosphorylation did not occur; and down-regulation of EGF receptors was slower. Selective mAb-mediated phosphorylation of tyrosine residues on EGF receptors was sufficient to activate phosphorylation of a SH2 group-bearing substrate, phospholipase C-gamma, indicating that serine/threonine phosphorylation is not required for EGF receptor kinase activity. These studies provide novel insights into the capacity of bivalent mAb to modulate EGF receptor function.

3T3 Cells↗
PubMed1993

Antitumor effect of anti-epidermal growth factor receptor monoclonal antibodies plus cis-diamminedichloroplatinum on well established A431 cell xenografts.

We have explored the therapeutic effects of anti-epidermal growth factor receptor monoclonal antibodies (MAbs) 225 and 528 on well established A431 epidermoid carcinoma xenografts, approximately 400 mm3 (1 cm in diameter) at the start of treatment. In previous reports we demonstrated that MAbs 225 and 528 prevented the growth of A431 cell xenografts in nude mice when treatment was begun on the day of tumor cell inoculation. Since anti-epidermal growth factor receptor MAb therapy of well established tumors was unable to retard growth, we explored combination therapy with MAb plus the chemotherapeutic agent cis-diamminedichloroplatinum (cis-DDP). Additive and concentration-dependent growth-inhibitory effects of MAb with cis-DDP were observed in cultures of A431 cells. Neither intensive treatment with 225 MAb (1 mg/mouse, i.p. on day 8 after tumor inoculation, and twice weekly for 4 weeks) nor a maximally tolerated single dose of cis-DDP [150 micrograms/25 g (6 mg/kg) mouse weight, i.p. on day 8] had significant effects on tumor growth. However, the two treatments in combination resulted in substantial xenograft growth inhibition, compared with both an untreated control group and animals treated with a single modality. When a second dose of cis-DDP (150 micrograms/25 g) was added after 10 days, combination therapy with 225 MAb produced striking antitumor effects. At the end of 1 month tumor xenografts had disappeared in all but one mouse, and no tumor relapses occurred during 6 months of observation. Identical results were obtained with anti-epidermal growth factor receptor MAb 528 in combination with cis-DDP. The results of these studies provide a novel approach to the treatment of well established tumor xenografts, which may have application in the therapy of human malignancies.

Animals↗
PubMed1993

Blockade of epidermal growth factor receptor function by bivalent and monovalent fragments of 225 anti-epidermal growth factor receptor monoclonal antibodies.

We have previously described anti-epidermal growth factor (EGF) receptor monoclonal antibodies (MAbs) which can block binding of transforming growth factor alpha (TGF-alpha) and EGF to receptors and inhibit activation of receptor tyrosine kinase. Studies with these MAbs involving cell cultures and nude mouse xenografts demonstrated their capacity to inhibit the growth of a variety of tumor cell lines, which express EGF receptors and TGF-alpha and appear to depend upon receptor activation for cell proliferation. To explore the mechanism(s) by which anti-EGF receptor 225 MAb inhibits cell proliferation, we have compared the activity of native 225 MAb with the response to bivalent 225 F(ab')2 and monovalent 225 Fab' fragments. Both native 225 MAb and its fragments could inhibit the binding of 125I-EGF to EGF receptors. Scatchard analysis revealed that the Kd of 225 F(ab')2 is comparable to that of 225 MAb (1 nM), whereas the Kd of 225 Fab' is 5 nM. Both bivalent 225 MAb and 225 F(ab')2 and monovalent 225 Fab' were able to completely inhibit TGF-alpha-induced EGF receptor tyrosine kinase activation, as assayed by autophosphorylation of tyrosine residues of EGF receptors on MCF10A nonmalignant human mammary cells, MDA468 human breast adenocarcinoma cells, and A431 human vulvar squamous carcinoma cells. The bivalent forms of MAb could inhibit proliferation stimulated by endogenous (autocrine) TGF-alpha in cultures of these three cell lines. They also blocked growth stimulation by added exogenous TGF-alpha in cultures of MCF10A cells and the growth-inhibitory effect of exogenous TGF-alpha upon MDA468 and A431 cell cultures. Monovalent 225 Fab' had weaker inhibitory effects upon the proliferation of these cell lines. To determine whether the in vivo antiproliferative activity of anti-EGF receptor MAb can occur without the participation of the Fc portion of MAb, the capacities of 225 F(ab')2 and native 225 MAb to inhibit growth of s.c. A431 cell xenografts were compared. Equimolar amounts of either 225 MAb or 225 F(ab')2 were administered at intervals equivalent to the half-lives of the molecules, to attempt to maintain comparable plasma levels. Both 225 MAb and 225 F(ab')2 inhibited A431 cell xenograft growth in a dose-dependent manner, with a more sustained response in the case of the intact antibody.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Activation and reactivation of the ATP-sensitive K+ channel of the heart can be modified by drugs.

Activation and reactivation of the ATP-sensitive K+ channel (IK.ATP) were studied with the patch-clamp technique in guinea-pig ventricular myocytes. The K+ channel openers, nicorandil and pinacidil, activated IK.ATP in an internal ATP-dependent manner. Both drugs increased the open probability of IK.ATP without changing the channel conductance. They prolonged lifetimes of bursts and shortened interburst intervals without influencing the fast gating within bursts. These effects were the opposite of those of internal ATP. However, the interaction between ATP and either nicorandil or pinacidil appeared not to be simple competition. We found that three carbonyl compounds--3,4-dihydroxybenzaldehyde, 2,3-dihydroxybenzaldehyde, and 2,4-dihydroxyacetophenone--could activate IK.ATP through an intracellular mechanism that was dependent upon the presence of ADP and Mg2+. It has been suggested that these three carbonyl compounds bind covalently to proteins to form a Schiff base, which may be responsible for their effects upon IK.ATP. Internal application of the proteolytic enzyme trypsin prevented both the spontaneous and Ca(2+)-induced rundown of the KK.ATP channel. Tryptic digestion did not change either the channel's sensitivity to inhibition by ATP nor the fast gating kinetics of IK.ATP. Internal application of an exopeptidase, carboxypeptidase A, but not leu-aminopeptidase, prevented the spontaneous and Ca(2+)-induced rundown of the IK/ATP channel, effects similar to those of trypsin treatment. These results suggest that the target site of trypsin digestion may be located on the carboxy (C)-terminal of the channel proteins or associated regulatory units.

Adenosine Triphosphate↗
PubMed1993

Cytoplasmic acidosis induces multiple conductance states in ATP-sensitive potassium channels of cardiac myocytes.

We studied the effect of cytoplasmic acidosis on the ionic conducting states of ATP-sensitive potassium channels in heart ventricular cells of guinea pigs and rabbits by using a patch-clamp technique with inside-out patch configuration. Under normal conditions (pH 7.4), the channel alternated between a closed state and a main open state in the absence of nucleotides on the cytoplasmic side. As internal pH was reduced below 6.5, the single channel current manifested distinct subconductance levels. The probability of the appearance of these subconductance levels was pH dependent with a greater probability of subconductance states at lower pH. A variance-mean amplitude analysis technique revealed two subconductance levels approximately equally spaced between the main open level and the closed level (63 and 33%). A current-voltage plot of the two subconductance levels and the main level showed that they had similar reversal potentials and rectification properties. An intrinsic flickering gating property characteristic of these ATP-sensitive channels was found unchanged in the 63% subconductance state, suggesting that this subconductance state and the main conductance state share similar ion pore properties (including ion selection and block) and similar gating mechanisms. The appearance of the subconductance states decreased as ionic strength was increased, and the subconductance states were also slightly voltage dependent, suggesting an electrostatic interaction between the protons and the negative surface charge in the vicinity of the binding sites, which may be close to the inner entrance of the ion pore. Proteolytic modification of the channel on the cytoplasmic side with trypsin did not abolish the subconductance levels. External acidosis did not induce subconductance levels. These results suggest that protons bound to the negatively charged group at the inner entrance of the channel ion pore may induce conformational changes, leading to partially reduced conductance states.

Adenosine Triphosphate↗
PubMed1993

Post-repolarization block of cardiac sodium channels by saxitoxin.

Phasic block of rat cardiac Na+ current by saxitoxin was assessed using pulse trains and two-pulse voltage clamp protocols, and the results were fit to several kinetic models. For brief depolarizations (5 to 50 ms) the depolarization duration did not affect the rate of development or the amplitude of phasic block for pulse trains. The pulse train data were well described by a recurrence relation based upon the guarded receptor model, and it provided rate constants that accurately predicted first-pulse block as well as recovery time constants in response to two-pulse protocols. However, the amplitudes and rates of phasic block development at rapid rates (> 5 Hz) were less than the model predicted. For two pulse protocols with a short (10 ms) conditioning step to -30 mV, block developed only after repolarization to -150 mV and then recovered as the interpulse interval was increased. This suggested that phasic block under these conditions was caused by binding with increased affinity to a state that exists transiently after repolarization to -150 mV. This "post-repolarization block" was fit to a three-state model consisting of a transient state with high affinity for the toxin, the toxin bound state, and the ultimate resting state of the channel. This model accounted for the biphasic post-repolarization block development and recovery observed in two-pulse protocols, and it more accurately described phasic block in pulse trains. The transient state after repolarization was predicted to have a dwell time of 570 ms, an on rate for saxitoxin of 16 s-1 micro M-1, and an off rate of 0.2 s-1 (KD = 12 nM). These results and the proposed model suggest a novel variation on phasic block mechanisms and suggest a long-lived transient Na+ channel conformation during recovery.

Animals↗
PubMed1993

Use-dependent block of Na+ currents by mexiletine at the single channel level in guinea-pig ventricular myocytes.

1. The mechanism of use-dependent block of Na+ current by mexiletine was studied at the single channel level in guinea-pig ventricular myocytes by the patch-clamp techniques. All experiments were performed using stimulation protocols to enable us to analyze the strict dependence of changes in channel properties on channel use. 2. In cell-attached patches, bath or pipette application of mexiletine (40 microM) produced a use-dependent reduction of the peak average current without changes in single channel conductance. Null sweeps were increased and the number of openings per sweep decreased with successive pulses, whereas no significant change in the mean open time was detected during the train. 3. Block by mexiletine became greater when pulse duration was extended beyond the period in which channels were open, suggesting that block progressed without channel opening. 4. At near threshold potentials, mexiletine decreased the later occurrence of first openings. Additionally, late openings were reduced in a use-dependent way. 5. We conclude that mexiletine binds to the inactivated closed states of the Na+ channel and then causes a failure of late openings as well as early, which results in null sweeps on subsequent depolarization.

Animals↗
PubMed1993

Properties of veratridine-modified single Na+ channels in guinea pig ventricular myocytes.

Modification of single Na+ channels by the alkaloid neurotoxin veratridine was investigated in guinea pig ventricular myocytes using the cell-attached configuration of the patch-clamp technique. Pipette application of veratridine (50 microM) induced long-lasting openings with two different single-channel conductances of 7.6 and 3.0 pS, in addition to normal type of short openings with a single-channel conductance of 16 pS. The veratridine-modified high- and low-conductance channels appeared commonly, and they could coexist with the normal one in the same patch. The open-time distributions for the high- and low-conductance channels could be fitted by a single exponential. The mean open time for the high- and low-conductance events ranged between 19.1 ms at -120 mV and 86.0 ms at -10 mV and between 4.5 ms at -120 mV and 16.2 ms at -10 mV, respectively. The closed-time distributions for the two conductance channels consisted of at least two components, and their values and voltage dependence were similar. External Ca2+ block resulted in an apparent reduction of unitary current amplitudes with a similar voltage dependence and affinity for Ca2+ in the high- and low-conductance channels. However, the low-conductance channel was more resistant to tetrodotoxin than the high one. The probability of simultaneous occurrence of the high and low events was equal to the product of the probabilities of occurrence of the high event times that of the low event. Furthermore, we observed modified channel openings after a normal opening for the two conductance channels and a modified one turning into a normal one for the high-conductance channel. It is concluded that veratridine induces the two different types of modified Na+ channels in cardiac myocytes and these are correlated with normal openings.

Animals↗
PubMed1993

Intracellular H+ and Ca2+ modulation of trypsin-modified ATP-sensitive K+ channels in rabbit ventricular myocytes.

ATP-sensitive K+ current (IK.ATP) channels are thought to play a role in the K+ efflux observed in cardiac ischemia. Intracellular acidosis is a prominent early effect in ischemia; therefore, the effects of acidosis on IK.ATP may have certain pathophysiological implications. Increased intracellular proton concentration (pHi) is known to regulate IK.ATP in frog skeletal muscle by increasing open probability. The pHi effect on IK.ATP is not clearly understood in heart because, unlike frog skeletal muscle, low pHi causes IK.ATP run-down in inside-out patches. This would tend to mask any opening effect of low pHi if it exists. Trypsin modification of IK.ATP has recently been shown to prevent run-down in inside-out patches. We used single channel recordings in inside-out patches to study IK.ATP after exposure to trypsin. After trypsin treatment, the open probability of IK.ATP was not sensitive to pHi in the absence of ATP. In the presence of ATP, however, a decrease in pHi consistently increased the open probability of trypsin-modified IK.ATP by reducing ATP inhibition. In the absence of ATP the mean open probability was 0.43 +/- 0.07 at pHi 7.4, and 0.5 mM ATP decreased the mean open probability to 0.03 +/- 0.04 at pHi 7.4, but mean open probability was significantly increased to 0.20 +/- 0.07 at pHi 6.3 (n = 7, p < 0.01). Ca2+ did not affect the activity of trypsin-modified IK.ATP in either the absence or presence of ATP at pHi 7.4. However, Ca2+ was able to antagonize the low pHi effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1993

Intracranial longitudinal splitting of facial nerve: a new approach for hemifacial spasm.

A new surgical technique for the treatment of hemifacial spasm consisting of longitudinal splitting of the facial nerve in the cerebellopontine angle is described. Thirty-three cases have been treated with good results. Follow-up of 20 cases for 1 year or more showed no recurrence or facial paresis. One case required a second operation. The novelty of this approach lies in its effectiveness in relieving the symptoms without running the risk of overmanipulating the aberrant artery.

Adult↗