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Biomedical subjects

M Chen

Publications and source records attributed to M Chen.

At least 811 records · Page 45Linked to original sources

Histamine stimulation of surfactant secretion from rat type II pneumocytes.

The present study examined the effect of histamine on the secretion of phosphatidylcholine, the predominant component of pulmonary surfactant from adult rat alveolar type II pneumocytes in primary culture. Histamine stimulated surfactant secretion in a time- and dose-dependent manner. At a concentration of 10 microM, histamine stimulated surfactant release by 5.2-fold over the basal secretory rate. The concentration producing half the maximal response for histamine-induced secretion was 70 nM. Histamine-induced secretion was blocked by both the selective histamine1 receptor antagonist pyrilamine and the selective histamine2 receptor antagonist cimetidine, but not by the beta-adrenergic antagonist alprenolol. Histamine activated adenylate cyclase and intracellular adenosine 3',5'-cyclic monophosphate (cAMP) production. These effects on adenylate cyclase and cAMP induced by histamine were inhibited by the H2 antagonist cimetidine. This would suggest that surfactant secretion was stimulated by histamine through H2 receptors and by cAMP. When histamine and isoproterenol were added concomitantly, the effects on phosphatidylcholine secretion were additive; however, there was no additive effect on adenylate cyclase activation. This coupled with H2 antagonist pyrilamine inhibition of histamine-induced secretion would suggest that histamine stimulated surfactant secretion through another mechanism in addition to a cAMP-dependent mechanism.

Adenylyl Cyclases↗

Vasopressin signal transduction in rat type II pneumocytes.

Previous studies demonstrate that in cultured type II pneumocytes, [Arg8]-vasopressin (AVP) stimulates surfactant secretion independent of adenosine 3',5'-cyclic monophosphate (cAMP). In the current study AVP stimulated a 50% loss of radioactive phosphatidylinositol 4,5-bisphosphate (PIP2) within 15 s. Consistent with AVP-induced PIP2 hydrolysis was an increased appearance of the two breakdown products 1,2-diacylglycerol (1,2-DAG) and inositol 1,4,5-trisphosphate (IP3). Also, AVP stimulated the appearance of radiolabel in phosphatidic acid (PA) suggesting that the conversion of 1,2-DAG to PA could be used for PIP2 resynthesis. The effects of AVP on PIP2 and IP3 were mimicked by the bioactive AVP fragment and inhibited by the specific AVP1 antagonist. The EC50 for AVP on IP3 production was 6 nM. AVP stimulated protein kinase C (PK-C) activity twofold over the basal activity of 0.74 +/- 0.07 nmol P.min-1.mg protein-1 but did not activate cAMP-dependent protein kinase activity. The AVP1 antagonist inhibited AVP activation of PK-C. Therefore, activation of the AVP1 receptor resulted in PIP2 hydrolysis for signal transduction, PK-C activation, and surfactant secretion.

Animals↗

Naloxone prevents increased vascular sensitivity in Goldblatt hypertensive rats.

These experiments were designed to determine if the opiate antagonist naloxone affects vascular sensitivity in 2K-1C hypertensive rats. Group 1 was 2K-1C hypertensive rats. Group 2 was 2K-1C rats given a naloxone infusion (100 micrograms/h) for 14 days. Group 3 received naloxone without clipping. Group 4 was untreated rats. At day 14 following clipping, systolic blood pressure was increased significantly in the 2K-1C rats. Those infused with naloxone showed a significant attenuation of the increase in blood pressure. Vascular responses to norepinephrine and KCl in the aortae from all groups were tested. Strips from untreated, 2K-1C rats were more sensitive to the contractile effects of norepinephrine than those from naloxone-treated, 2K-1C rats, and from both groups of normotensive rats. Contractile responsiveness to depolarizing concentrations of KCl were not different among the four groups. These data demonstrate that naloxone attenuates the development of renal hypertension and prevents the increase in vascular responsiveness to norepinephrine.

Angiotensin II↗

[Effect of monoamine neurotransmitters in the hypothalamus in a cortisol-induced rat model of yang-deficiency].

Eight monoamine neurotransmitters in hypothalamus of normal and cortisol-induced Yang-deficiency rats were measured with HPLC-ECD. These neurotransmitters included: (1) Noradrenaline (NA); (2) Adrenaline (A); (3) 3-methoxy-4-hydroxyphenyl glycol (MHPG); (4) 3,4-dihydroxyphenylacetic acid (DOPAC); (5) Dopamine (DA); (6) 5-hydroxyindole-3-acetic acid (5-HIAA); (7) Homovanillic acid (HVA); and (8) Serotonin (5-HT). With the mobile phase of 10% methanol-0.15 M chloroacetic acid-sodium hydroxide buffer, the neurotransmitters might be well separated, the sensitivity was similar to that of gas chromatography-mass spectrogram with the lower limit of 0.1 ng, this assay was simple and might be accomplished with half an hour. The Yang-strengthening Chinese herbs Radix Aconiti Praeparata, Cortex, Cinamomi, Epimedium brevicorum and Herba Cistanchis were used in the study and the following were founded: (1) In the hypothalamus of cortisol-induced Yang-deficiency rat NA decreased and a increased when compared with that of the normal controls (both P less than 0.05). (2) After 4 weeks of administration of Yang-strengthening herbs, the NA and A of the Yang-deficiency rats returned to nearly normal and it suggested these herbs have the effect of "supporting the right and recovering the source"; DA markedly increased both in control rats and Yang-deficiency rats (P less than 0.05, P less than 0.001 respectively); DOPAC obviously decreased both in control rats and Yang-deficiency rats (P less than 0.001); 5-HT and 5-HIAA increased in the control rats (both P less than 0.001) and HVA significantly decreased in Yang-deficiency rats. (3) The ratio of DA/DOPAC and 5-HT/5-HIAA markedly increased both in the control and Yang-deficiency rats after using Yang-strengthening herbs (P less than 0.01-0.001) and it suggested Yang-strengthening herbs could inhibit the activity of monoamine oxidase in hypothalamus.

3,4-Dihydroxyphenylacetic Acid↗

[Clinical applications of percutaneous transluminal coronary laser angioplasty].

Seven cases of coronary heart diseases underwent percutaneous transluminal coronary laser angioplasty were described. Nd:YAG laser energy was delivered by metallic-capped fiberoptic. Significant reduction of narrowing was observed at the laser sites (LAD 4 cases, LCX 1 case and RCA 2 cases) after this procedure (from 89.9% to 49.9%, P less than 0.01). Satisfactory results were achieved in all cases but one, who had acute occlusion when added PTCA after laser irradiation. The indications, maneuvers and possible complications about percutaneous transluminal coronary laser angioplasty were also discussed in this article.

Adult↗

[Percutaneous transluminal atherectomy in the treatment of occlusive peripheral vascular disease].

Percutaneous transluminal atherectomy (ATH) can remove the obstructing atheromatous material and may overcome the limitations of balloon angioplasty for the treatment of occlusive peripheral vascular disease. This is the first case reported in China using the Simpson rotational atherectomy device in a patient with total occlusion of left superficial femoral artery. The significant improvement in lumen was achieved by removing a tissue specimen of 14 x 4 x 3 mm3 followed by a balloon angioplasty, which reduced the residual luminal narrowing further from 50% to 20%. No acute complication was found and the patient was discharged from hospital one week after the procedure. Our results suggests that the ATH might be an effective and safe treatment for occlusive peripheral vascular disease.

Angioplasty, Balloon↗

[Chemical constituents of the seed oil of Astragalus complanatus R. Brown].

beta-sitosterol and fatty acids were obtained from the oil of seeds of Astragalus complanatus. The fatty acids were separated and their molecular weights determined by GC-MS. Fourteen of them were identified as heptenoic acid, tetradecanoic acid, pentadecanoic acid, hexadecanoic acid, octadecenoic acid, octadecanoic acid, octadecadienoic acid, linolenic acid, eicosanoic acid, eicosenoic acid and docosanoic acid, etc.

Drugs, Chinese Herbal↗

[Anti-arrhythmic effects and electrophysiological properties of Ophiopogon total saponins].

The arrhythmias induced by chloroform-epinephine, BaCl2, and aconitine were prevented and antagonized by Ophiopogon total saponins (OTS) which were extracted from the root of Ophiopogon japonicus (Thunb) Ker-Gawl. The incidence of ventricular arrhythmia produced by ligation of the left anterior descending coronary artery was effectively decreased without any changes in the hemodynamic indices of dogs. The electrophysiological effects of OTS in vivo and in vitro were studied by means of contact electrode and intracellular microelectrode techniques. The results showed that OTS shortened APD10, APD50, APD90; decreased APA and Vmax of both monophasic and transmembrane action potentials. OTS also increased the ERP/APD ratio and prevented or abolished the arrhythmikinesis provoked by ouabain and aconitine. The anti-arrhythmic properties of OTS lead us to draw an inference that the anti-arrhythmic mechanism may be related to the blocking of sodium and calcium channels.

Aconitine↗

[Curative effects of modified xiao-jin pills and chemotherapy after surgery in patients with mid and late phase gastric cancer].

From 1986, the authors mainly used Modified Xiao-Jin Pills (MXJP) added with chemical treatment to cure patients in mid and late phase of gastric cancer after operation. 72 patients were verified as gastric cancer by pathological section and phases were divided according to TNM classification which was revised by the national cooperative group of gastric cancer in 1978. The patients were randomly divided into curative and control groups. The two groups were basically similar in sex, age, clinic pathological phase and operation. One month after operation, the two groups received the same treatment except that the control group did not take MXJP. The indexes of observation consisted of living rate, substance of tongue and 5 indexes of blood coagulation (AT-III, Fn, FA, VIII R:Ag and beta TG). The curative effects showed that MXJP could enhance gastric cancer patients living rate for 1, 1.5 and 2 years among which it was obvious for phase IV's gastric cancer patients to enhance 1 year's living rate (P less than 0.05), and lower the negative rate of substance of tongue (P less than 0.001). The indexes of AT-III, Fn FA and VIII R:Ag and beta TG of gastric cancer patients had changed for the better (P less than 0.05). The results showed that MXJP can enhance the capacity of body to antagonize coagulation fibrinolysis, remove blood stasis and further enhance the living rate of patients. MXJP has better curative effects of short term.

Adult↗

In situ phosphorylation of platelet actin-binding protein by cAMP-dependent protein kinase stabilizes it against proteolysis by calpain.

To identify the protein kinase that is responsible for catalyzing phosphorylation of actin-binding protein (ABP) in platelets, we have examined the effects of protein kinase C and cAMP-dependent protein kinase on this process. We found that purified platelet protein kinase C from platelets was unable to phosphorylate ABP in vitro. However, a crude platelet kinase preparation phosphorylated ABP in the presence of cAMP, but not in the presence of Ca2+/phosphatidylserine. Fresh platelet plasma membranes incubated with [gamma-32P]ATP phosphorylated ABP in the presence of cAMP and the process was blocked by a cAMP-dependent protein kinase inhibitor; ABP phosphorylation induced by prostaglandin E1 (PGE1) appeared to be reduced by the subsequent addition of thrombin. These results strongly suggest that in situ ABP is phosphorylated by activated cAMP-dependent protein kinase when platelet function is inhibited by PGE1. Furthermore, in the PGE1-treated platelets, ABP was proteolyzed at a slower rate than in control platelets when they were lysed with Triton in the absence of EGTA. Partially purified ABP was proteolyzed by calpain in vitro at a slower rate as well. It was demonstrated that ABP from PGE1-treated platelets recovered its sensitivity to calpain after ABP was incubated with a protein phosphatase that had been purified from platelets. We postulate that ABP is stabilized against proteolysis in response to cAMP-elevating agents and that this blocks cytoskeleton reorganization.

Blood Platelets↗

In vivo [31P]NMR studies on the influence of age on rat brain hypoxia.

In this paper the response of cerebral phosphate metabolism to mild hypoxia in young, medium and old rats has been studied via in-vivo [31P]nuclear magnetic resonance (NMR). It was found that the young adults (5-6 months) were more sensitive to this mild stress than either the mature adult (11-12 months) or senescent (23-24 months) rats even though the depth of hypoxia (paO2 = 45-55 mm Hg) was equal for all age groups. They displayed an earlier onset of acidosis, a greater fall in PCr and larger rise in Pi. This response is presumably an attempt to maintain adequate adenosine triphosphate (ATP) levels via anaerobic glycolysis. In contrast, mature adults and senescent adults appear to be able to maintain ATP levels by increasing mitochondrial rates. Acidosis is less severe as are drops in PCr and rises in Pi. Recovery is less complete for the young rats: Pi levels remain high while PCr and pHi levels stay low after normoxia has been reinstigated. All metabolite levels in the mature and senescent adults return to within 10% of control levels. All the data were analyzed and differences were found to be statistically significant. This study reveals that, contrary to popular belief, mature and old rats respond more favorably to reduced O2 than younger individuals. This is due to a more severe anaerobic acidosis in the latter age group. Speculations to explain this disparity are based on the fact that previous in-vitro studies involve systems that are totally or partially disconnected from the organism will not account for important feedback control present in an in-vivo system as studied here.

Aging↗

Structural plasticity at identified synapses during long-term memory in Aplysia.

We have used the gill- and siphon-withdrawal reflex of Aplysia californica to determine the morphological basis of the prolonged changes in synaptic effectiveness that underlie long-term habituation and sensitization. We have found that clear structural changes accompany behavioral modification and have demonstrated that these can be detected at the level of identified sensory neuron synapses, a critical site of plasticity for the short-term forms of both types of learning. These alterations occur at two different levels of synaptic organization and include (1) changes in focal regions of synaptic membrane specialization--the number, size and vesicle complement of sensory neuron active zones are larger in sensitized animals and smaller in habituated animals compared with controls--and (2) a parallel but more dramatic and global trend involving modulation of the total number of presynaptic varicosities per sensory neuron. Quantitative analysis of the time course over which these structural alterations occur during sensitization has further demonstrated that changes in the number of varicosities and active zones persist in parallel with the behavioral retention of the memory. This increase in the number of sensory neuron synapses during long-term sensitization in Aplysia is similar to changes in the number of synapses in the mammalian brain following various forms of environmental manipulations and learning (Greenough, 1984). Therefore learning may involve a form of neuronal growth across a broad segment of the animal kingdom, thereby suggesting a role for structural synaptic plasticity during long-term behavioral modifications.

Animals↗

Aberrant response in vitro of hormone-responsive prostate cancer cells to antiandrogens.

Antiandrogens are in use alone and in combination with other agents as hormonal therapy for prostate cancer. We conducted studies on the androgen-responsive human prostate cancer cell line LNCaP to determine the direct effects of three antiandrogens (hydroxyflutamide, RU23908, and cyproterone acetate) on hormone-responsive human prostate cancer cells in culture. Dihydrotestosterone (DHT) stimulated the growth of LNCaP cells in a dose-dependent fashion. These cells contained approximately 31,000 high-affinity (Kd = 9 x 10(-10) M) androgen binding sites per cell. In the absence of any androgenic stimulation, all three antiandrogens tested showed agonistic properties by increasing the cell number and uptake of [3H]-thymidine. Competitive uptake studies using [3H]-R1881, a nonmetabolized androgen, showed that the three antiandrogens inhibited specific R1881 uptake with IC50s of 0.9 x 10(-7) M for hydroxyflutamide, 2 x 10(-7) M for RU23908, and 1 x 10(-7) M for cyproterone acetate. It is not known whether these unexpected agonistic effects are due to an altered receptor, previously unmasked agonistic properties of the antiandrogens, or emergence of a hypersensitive clone of cells.

Androgen Antagonists↗

Dissection of functional domains of adenovirus DNA polymerase by linker-insertion mutagenesis.

Linker-insertion mutations were introduced into the cloned adenovirus DNA polymerase gene and the functional effects on the initiation and elongation of DNA in vitro were measured. Essential regions of the polymerase appear to be scattered in patches across the entire molecule and are not limited to the five regions of homology shared with a variety of other replicating polymerases. Thus, the adenovirus DNA polymerase presumably contains active sites that must be formed by distant interactions across the polymerase molecule.

Adenoviruses, Human↗

Comparisons of body composition derived from anthropometric and bioelectrical impedance methods.

This study compared bioelectrical impedance analysis (BIA) measurements with current bedside techniques for determination of body composition in 18 normal volunteers to evaluate the relative usefulness of these methods as adjuncts to assessment in surgical nutrition. Anthropometrics (weight, height, and two skinfold thicknesses) and age and sex were used to derive body density (D) or total body water (TBW) by two methods. Method 1: D was calculated from the logarithm of skinfold thickness according to Durnin and Womersley, adapted for age and sex. Method 2: TBW was calculated from height, weight, and sex according to Hume and Weyers. Resistance and reactance were measured with a four terminal impedance plethysmograph; from these data plus height, weight, and sex, lean body mass (LBM) was derived. In each instance, Siri's and Pace and Rathburn's equations were used to derive the remaining parameters of body composition: D, total body fat (TBF), TBW, and LBM. Using the paired t-test, no statistically significant differences were seen in any parameter determined by the different methods. These results show that D, TBW, TBF, and LBM in a population of healthy individuals under steady-state conditions can be estimated by anthropometric-derived formulas with the same relative accuracy as that provided from estimates based upon BIA measurements.

Adult↗

Functional relevance of the microheterogeneity of active renin.

We previously demonstrated the presence of six active forms of renin in rats, based on their isoelectric points (pI). Intravenous or intraventricular injections yielded different renal effects with the different forms. Additional work is presented supporting the hypothesis that these forms are functionally different. Renin form 2 (pI = 5.7), form 4 (pI = 5.2) or form 6 (pI = 4.8) was infused intravenously (IV) in Spague-Dawley rats. The total renin infused over 30 minutes was the amount that could generate 1000 ng angiotensin I (Ang I)/h/100g body weight. Arterial blood pressure, urine volume, sodium, and potassium excretion were determined at 15-minute intervals. Plasma renin activity (PRA) and plasma aldosterone concentrations were measured 45 minutes after the start of infusion of renin forms. Infusion of renin form 4 increased urine volume and sodium excretion significantly. Renin forms 2 and 6 were without effect on renal excretion in spite of the fact that the same activity was infused. Both PRA and aldosterone concentrations after renin infusions were similar for all groups. Nonrenin renal protein with the same pI as form 4 was used as a control. This preparation was inactive and implies that our data with renin form 4 were not the result of contamination with a nonrenin protein having a pI of 5.2. In addition, the urinary responses could not be attributable to change in renal perfusion pressure as arterial blood pressure was not altered. These data support the hypothesis that there are functional differences among the different renin forms.

Animals↗

Organ culture of frog muscle: maintenance of mass, enzyme levels, and contractile force.

This paper describes an organ culture system that maintains frog sartorius muscles in good condition for 5 days. In the absence of serum and insulin, muscles maintained at approximately 93% of resting length atrophied with significant decreases in dry weight, protein content, and contractile force, and in the levels of activity of citrate synthase, lactate dehydrogenase, and creatine kinase. Inclusion of 1.0 mU/ml of insulin in the culture medium prevented the decreases in muscle mass, twitch tension, and citrate synthase activity and minimized the decreases in lactate dehydrogenase, creatine kinase, and tetanic tension. Inclusion of 10% serum, in addition to 1 mU/ml insulin, in the medium did not have clear cut additional benefits. Stretching muscles to 110% of resting length (L0) resulted in marked deterioration with decreases in total protein, enzyme levels, and contractile force. Keeping muscles at approximately 93% L0 was as effective as maintenance at L0 in preventing atrophy and loss of contractile force and enzyme activities. This organ culture procedure, which maintains frog sartorius muscle in good condition without serum for at least 5 days, may provide a useful model for studying the regulatory mechanisms responsible for a variety of adaptations in muscle.

Animals↗