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Biomedical subjects

C L Chang

Publications and source records attributed to C L Chang.

At least 19 recordsLinked to original sources

Change in protein kinase C activity on day 5 of decidualization in pseudopregnant rats.

The specific activities of protein kinase C (PKC) and protein tyrosine kinase (PTK) were determined in the decidualized uterine tissue of pseudopregnant rat on day 5 of decidualization. We found that the activity of the cytosolic PKC was significantly lower in decidualized uterine tissue as compared with that of the controlateral untreated uterine tissues (1.5 +/- 1.4 versus 57.5 +/- 4.1 pmol 32P/min/mg, P < 0.001), while the PKC activity in particulate fraction was not significantly different (124.8 +/- 14.5 versus 236.8 +/- 88.6 pmol 32P/min/mg) concerning protein concentration. The reduced expression of the cytosolic PKC activity was observed on all five individual rats. In contrast, the decidualized uterine tissue showed similar cytosolic PTK activity as compared with the controlateral untreated uterine tissues (20.1 +/- 3.0 versus 20.6 +/- 3.2 pmol 32P/min/mg protein), and similar in particulate PTK activity (42.5 +/- 9.0 versus 36.8 +/- 5.1 pmol 32P/min/g protein). These results indicate that cytosolic PKC activity may be involved in modulation of decidual growth.

Animals

Attenuation of the catecholamine responses by electroacupuncture on Jen-Chung point during postoperative recovery period in humans.

In this study, Jen-Chung (J-C) point was stimulated by electroacupuncture (EA) in 10 patients, and by placebo treatment in 10 controls, immediately after termination of inhalation for 15 min. During the postoperative recovery period, plasma catecholamine (CA) levels were assessed before (0) and 15 and 30 min after treatment. The time from cessation of inhalation to the first eye opening and to extubation did not differ between groups. The plasma catecholamine levels increased by 30% from 0 to 15 min in the control group but decreased by 6% in the EA group. The levels at 30 min were approximately the same as at time 0. The change in catecholamine levels from 0 to 15 min was significantly lower (P < 0.02) in the EA groups than the control group.

Acupuncture Points

Clinical application of transorotracheal tube tracheal insufflation of oxygen in patients undergoing simple video-assisted thoracoscopic surgery.

Video-assisted thoracoscopic surgery (VATS) has been performed during ganglionectomy and bullectomy and usually requires a collapsed or immobilized lung. Transtracheal insufflation of oxygen (TRIO) maintains an immobilized lung, adequate oxygenation, and partial CO2 elimination but has never been used for VATS. We have simplified the TRIO design with a catheter inserted through the lumen of the orotracheal tube in what we call "transorotracheal tube TRIO" (TRIO-TOTT) and investigated its clinical use on simple VATS. Eleven patients undergoing bullectomy for primary simple pneumothorax (PSP) were studied. During the performance of VATS, a 12-gauge suction catheter was inserted as our modification and connected to the gas outlet of an anesthetic machine. The flow rate of oxygen was maintained at 10 L/min. Blood gas was collected prior to TRIO-TOTT, during TRIO-TOTT at 5, 10, 15, and 20 min, and 5 min after TRIO-TOTT. The blood gas data showed excellent oxygenation while the PaCO2 increased at a rate of 1.2 mm Hg/min compared to 3-4 mm Hg/min for apnea oxygenation. After 20 min, the mean +/- SEM PaO2 and PaCO2 were 428 +/- 27 and 65.0 +/- 2.6 mm Hg, respectively. We conclude that TRIO-TOTT is a simple, safe, and effective ventilation method for simple VATS.

Adolescent

Nucleus accumbens dopaminergic mediation of protection against gastric mucosal ulcerations by cold-restraint stress in the male hyperprolactinemic rats.

An investigation was undertaken to study the relationship between change in gastric lesion induced by cold-restraint stress and brain dopamine (DA) activity in male rat with chronic hyperprolactinemia. Male rats of Wistar strain were divided into two groups: one received extra two pieces of anterior pituitary (AP) from its littermates, the other grafted with several pieces of muscle served as control. Experiment I: From the 5th day to 40th day after transplantation, the levels of serum prolactin (PRL) in the AP-grafted group were higher than those of control (p < 0.05 or p < 0.01). Experiment II: On the 40th day after transplantation, AP-grafted and control rats were restrained and placed supine in a ventilated refrigerator with an ambient temperature of 5 degrees C for 3 hrs. Although gastric mucosal ulceration was observed in both groups, the ulcer index (including total number and length of gastric mucosal ulceration) was lower in AP-grafted group than that in control group (p < 0.05 or p < 0.01). Experiment III: On the 40th day after transplantation, all rats were divided into AP-grafted and muscle-grafted rats. Subsequently, they were allowed to expose to cold-plus-restraint stress and unstress (room temperature: 24 +/- 1 degrees C) respectively. After stress and unstress, all animals were immediately sacrificed by decapitation, the brains were dissected with Palkovits' micropunch technique. DA and its metabolites, DOPAC content in Nucleus accumbens (NAc) area of brain were assayed by HPLC with electrochemical detection. These results showed that concentrations of DA, DOPAC and their ratios (DOPAC/DA) in the NAc area of brain, were not statistically different under room temperature condition between muscle-grafted and AP-grafted rats. The DOPAC/DA ratio in both groups showed significant increase in the brain's NAc area under cold-restraint stress condition as compared with unstress condition. But AP-grafted rats exhibited significantly higher DOPAC content in the brain's NAc area when compared with muscle-grafted rats under cold-restraint stress condition (171.7 +/- 22.1 versus 101.5 +/- 14.2 ng/mg protein, p < 0.05). According to these findings, we suggest that reduced effect of chronic high serum PRL level from extra pituitary grafts on gastric mucosal ulceration produced by cold-restraint stress is probably mediated via Nucleus accumbens dopaminergic neuronal mechanism.

Animals

Comparison of oral controlled-release morphine with transdermal fentanyl in terminal cancer pain.

BACKGROUND: Controlled-release morphine (MST) given twice daily provides a simpler and more convenient treatment regimen than 4-hourly opioid administration for the control of cancer pain. Recently, a new formulation of transdermal fentanyl (TDF) has been developed which provides a new route for the treatment of cancer pain. The present study was designed to compare the analgesic efficacy, safety and adverse effects of MST and TDF in the management of chronic cancer pain. METHODS: In this open, comparative and randomized study, patients were treated with oral morphine hydrochloride immediate-release (MHIR) in the stabilization phase and then the prescription was switched to MST or TDF for 14 days in the treatment phase. Oral MHIR was provided as rescue medication for breakthrough pain. Assessments of the pain intensity, pain frequency, degree of pain improvement, profile of mood states, quality of sleep, activity status and adverse effects were performed before and after the stabilization phase and before and after the treatment phase. RESULTS: Forty of 47 cancer patients completed the study with 20 patients in each group. There were significant (p < 0.05) improvements in pain intensity, pain frequency, mood states and quality of sleep in both groups before and after treatment, while improvement in the activity status was not significant. No specific adverse effects were encountered except for drowsiness which occurred in 6 patients treated with MST and 5 treated with TDF (p < 0.05). Insomnia was significantly improved (p < 0.05) with both regimens compared with that in the period before treatment. There were no significant differences between the two study groups in analgesic efficacy or adverse effects. CONCLUSIONS: These results suggest that TDF and MSt are safe and effective analgesics for the management of chronic cancer pain. However, TDF provides a simpler and more convenient treatment for those patients with severe nausea, vomiting or dysphagia.

Administration, Cutaneous

NitroG-L-arginine methyl ester reduces the minimal alveolar concentration of isoflurane in rabbits.

BACKGROUND: Recently, some studies suggested that nitric oxide (NO) plays a role as a mediator in the central nociceptive pathways and is possibly involved the mechanisms of anesthesia and wakefulness. Inhibition of the L-arginine-NO pathway in the central nervous system may result in an anesthetic, analgesic, or sedative effect. The aim of the present study was to evaluate the effects of the nitric oxide synthase inhibitor (NOSI), nitroG-L-arginine methyl ester (L-NAME), on the threshold for isoflurane anesthesia in rabbits. METHODS: Sixteen New Zealand rabbits were randomly divided into two groups, with eight rabbits in each group. In the study group, a dose of L-NAME 30 mg/kg was injected i.v. daily as pretreatment on three consecutive days, and the fourth dose of L-NAME was given 30 min before the study began. Normal saline was given to the control group. Data of minimal alveolar concentration (MAC), blood pressure (BP), and heart rate (HR) were collected from both groups. Vital signs, such as EtCO2, O2 saturation, and temperature, were maintained within the normal range. All data were described as mean +/- SEM. Statistical analysis was performed using Student's t-test, where p < 0.05 was considered significant. RESULTS: MAC of isoflurane in the control group was 1.90 +/- 0.12%. MAC of the L-NAME group was 1.70 +/- 0.22%, significantly lower than the control group (p < 0.05). CONCLUSIONS: Our preliminary result shows that the MAC of isoflurane in animals treated with L-NAME was lower than that in the control group. It is suggested that inhibition of the nitric oxide pathway may enhance the effect of isoflurane.

Anesthetics, Inhalation

Expression of human MutS homolog 2 (hMSH2) protein in resting and proliferating cells.

The hMSH2 protein plays an important role in the DNA mismatch repair system. Since this system is involved in the correction of errors that occur during DNA replication, we studied the expression of hMSH2 protein in resting and DNA-replicating cells, as well as through the cell cycle in cell types with different growth characteristics. Using Western blot analysis, we showed that hMSH2 protein was detectable in resting peripheral blood lymphocytes and thymocytes. However, when these cells were induced to proliferate, the protein level increased at least 12-fold. In cell-cycle dependent expression studies we chose two DNA mismatch repair proficient cell lines (HEL and HeLa-S3), and flow cytometry was used to monitor cell-cycle progression. At every phase in the cell cycle, the steady-state level of hMSH2 was higher than in resting lymphocytes or thymocytes, and only minor variations of expression level were observed through the cell cycle. In particular, a two to fourfold decrease in hMSH2 expression occurred at G1 in HEL and at early S phase in HeLa-S3, but higher expression levels resumed during the replicative and postreplicative phases of the cell cycle. Interestingly, hMSH2 protein expression decreased fourfold when HEL cells were induced to differentiate along the megakaryocyte lineage, when continuous DNA replication occurs without mitosis. These results suggest that a basal level of hMSH2 protein expression is necessary for resting and differentiated cells, and that increased hMSH2 protein expression is required when DNA replication is activated and followed by mitosis.

Cell Cycle

A nucleoside diphosphate kinase A (nm23-H1) serine 120-->glycine substitution in advanced stage neuroblastoma affects enzyme stability and alters protein-protein interaction.

A high level of nucleoside diphosphate kinase A (NDPK A/nm23-H1) in neuroblastoma is associated with advanced stage disease. We have also found a serine 120-->glycine substitution in NDPK A and/or amplification of the nm23-H1 gene in advanced stage neuroblastomas. Serine 120, a highly conserved residue, is located in proximity to histidine 118 which forms a phosphorylated intermediate essential for NDPK activity. The effect of Ser120-->Gly substitution on the biochemical properties of NDPK A was investigated. Phosphate-transferase activity was lower in the recombinant mutant NDPK A and in the immunoprecipitated complex consisting of NDPK A and NDPK B prepared from a neuroblastoma tumor containing the mutation, relative to the wild-type. There was a significant decrease in the enzyme stability toward urea- or temperature-induced denaturation for the recombinant mutant NDPK A and in an immunoprecipitate from a tumor containing the mutation. Recombinant NDPK A containing the Ser120-->Gly mutation exhibited reduced hexameric and increased dimeric oligomerization relative to the wild-type. Moreover a 28 kDa cellular protein was detected, that co-precipitated with the mutant but not wild-type NDPK A. The altered properties of the mutant protein may have relevance to a role for NDPK A in neuroblastoma progression.

Base Sequence

Capillary liquid chromatography coupled with an ion trap storage/reflectron time-of-flight mass spectrometer for structural confirmation of three recombinant protein isoforms.

Packed-capillary high-performance liquid chromatography (HPLC) was successfully coupled with an ion trap storage/reflectron time-of-flight mass spectrometer (LC/IT/reTOFMS) through an electrospray ionization interface for protein structural elucidation. Using the total-ion storage capabilities of the trap over a broad mass range and the high sensitivity from the packed capillary column with i.d. as small as 250 microns, high sensitivity peptide mapping in the low picomole range was demonstrated for the structural confirmation of three recombinant human nucleoside diphosphate kinase isoforms (NDPK, E.C. 2.7.4.6). A strategy combining chemical/enzymatic digestions as well as collisionally-induced dissociation (CID) in the electrospray source was successfully employed to infer the minor primary structural differences among the three recombinant proteins. This high sensitivity was achieved while also maintaining a resolution of nearly 1500 for mass identification using the capabilities of the IT/reTOF device. A point mutation of serine 120 to glycine was verified between the wild-type NDPK A and its mutant (delta m = 30 u) by both selected-ion monitoring and ion-source CID of the protein fragment containing the mutation site. For the structural confirmation of the sequence of NDPK A and B (88% homology), two sets of chemical/proteolytic digests were generated independently and followed by LC/MS analysis of the molecular weight of each protein-generated fragment. The complementary information from the two chromatographic analyses allowed for sequence verification of the two protein isoforms. The experiments clearly demonstrated that the high concentration sensitivity of the capillary high-performance liquid chromatographic separation together with the advantages of the IT/reTOF mass spectrometer could provide a low-cost, high-performance facility for protein analysis.

Amino Acid Sequence

Inhibitory effect of propofol on sympathetic neurotransmission results in changes of plasma neuropeptide Y in rats.

1. The effects of propofol on sympathetic neurotransmission and changes of plasma level of neuropeptide Y-like immunoreactivity (NPY-ir) were investigated in rats. 2. Intraperitoneal injection of propofol into rats lowered the systemic blood pressure and plasma NPY-ir in a dose-dependent manner. 3. Decrease of plasma NPY-ir induced by propofol was not modified in adrenalectomized rats. In the activation of adrenergic neurotransmission by a ganglionic nicotinic agonist, elevation of plasma NPY-ir was also reduced by propofol indicating the direct effect on peripheral adrenergic nerve terminals. 4. Plasma level of NPY-ir reversed in parallel with the recovery of anaesthesia induced by propofol. After an intracerebroventricular injection of propofol into the rats, both the lowering of plasma NPY-ir and the induction of anaesthesia were observed. Thus, a central nervous system effect of propofol can also be considered in its effect on plasma NPY-ir. 5. The data suggest that propofol has the ability to lower plasma NPY-ir in rats through an inhibition of adrenergic neurotransmission via central nervous pathway and/or peripheral nerve terminal blockade.

Adrenalectomy

Reliability of data from proxy respondents in an international case-control study of cardiovascular disease and oral contraceptives. World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception.

STUDY OBJECTIVES: To evaluate the reliability of data supplied in a case-control study by proxy respondents for cases who were too ill to do so themselves. DESIGN: A hospital based, case-control study of the current use of oral contraceptives (OC) and cardiovascular diseases. Data from "true" controls matched to a subset of cases were compared with those supplied by proxy respondents about the true controls. SETTING: Hospitals in 21 centres from Africa, Asia, Europe, and Latin America. PATIENTS AND PARTICIPANTS: For a subset of cases, 403 pairs of controls-one "true" and one proxy-were interviewed. "True" controls were matched by age, place, and time of admission and were admitted with 1 of 27 permissible diagnoses not associated with OC use. Proxy controls were either relatives or friends of true controls. MAIN RESULTS: Levels of concordance between data from proxy and true controls were high for most variables regarding recent events, including current OC use, but were greatly diminished when detailed information, particularly from the past, was required. Husbands were usually the best proxy, although this was question-specific. The sensitivity and specificity of proxy responses were 93% (95% confidence intervals: 77%, 99%) and 100% (98%, 100%) respectively, for current use of OC. Assuming the misclassification of current OC use by proxy cases is similar to that produced by proxy controls, the estimated impact of using proxy data on risk estimates associated with current OC use was to bias the overall estimate of risk of stroke by less than 3% and the risks of both acute myocardial infarction and venous thromboembolism by less than 1%. CONCLUSIONS: Friends or relatives, and particularly husbands, provided reliable information when used as proxy respondents for young women. The estimated impact of misclassification by proxy respondents on overall risk estimates in the WHO collaborative study was less than that which would have arisen if information from proxy respondents had not been used.

Adult

Heterogeneous responses to the long-term treatment of active acromegaly with octreotide.

To study GH response to the long-acting somatostatin analogue, we treated 11 actively acromegalic patients with octreotide (Sandostatin), 100 micrograms, sc, tid, for six months. Their endocrinological outcomes and clinical improvements varied. The 11-h GH secretory profiles on pretreatment day confirmed the hypersecretion of GH in all patients. Three hours after the first dose of octreotide, serum GH declined rapidly to levels below 5 ng/ml in all but two patients who failed to normalize their serum GH. In spite of the subsequent doses, there was no further suppression in serum GH. Drug resistance with GH rebound developed in some patients after three months of continued treatment. The paradoxical serum GH rises in response to oral glucose or iv TRH detected before the treatment in all patients attenuated or disappeared after the 6-month octreotide therapy; an exceptional case was one of the above-mentioned two patients, whose serum GH was stimulated more than before by glucose and TRH at the end of therapy. Serum insulin-like growth factor I (IGF-I) levels of all patients showed a significant reduction after 6-month treatment, but their mean values remained abnormally high. There were no intolerable adverse side effects; some patients, however, experienced pain at the injection site, passage of loose stool, and incidence of new gall stone or intrahepatic lesions on octreotide therapy. We concluded that octreotide was a useful long-term adjunctive therapeutic agent for patients with active acromegaly, but that a high degree of response heterogeneity including total refractoriness would be expected.

Acromegaly

Prognostic factors of primary aldosteronism.

BACKGROUND: Primary aldosteronism (PA) is a rare but potentially curable cause of hypertension. Between October 1982 and November 1994, 30 patients of PA received unilateral adrenalectomy with a long-term follow up (mean:60.3 months). Nineteen (63.3%) cases were cured (Group 1); 11(36.7%) cases were improved (Group 2). The purpose of this study was to determine prognostic factors after surgery in patients with PA. METHODS: A retrospective analysis was performed regarding age and sex of the patients, duration of hypertension, family history of hypertension, preoperative blood pressure, plasma aldosterone concentration (PAC), plasma renin activity (PRA) and efficacy of spironolactone on blood pressure between both groups. End-organs (including kidney, heart, retina and brain) involvement was evaluated and compared. Adrenalectomy and renal biopsy specimen for pathology were similarly evaluated. RESULTS: The duration of hypertension was longer in Group 2 than in Group 1 (8.18 +/- 4.94 vs 5.21 +/- 4.24 years). The efficacy of spironolactone on blood pressure (BP) was positive in 81.8% of Group 1 and 16.7% of Group 2. Adrenal cortical adenoma in 24 cases with a cure rate of 70.8% (17/24) and adrenal cortical macronodular hyperplasia in 6 cases with a cure rate of 33.3% (2/6) were noted. Group 2 had more end-organs involvement than Group 1. The severity of histopathological change of the renal biopsy was similar. CONCLUSIONS: This study suggests that preoperative response of blood pressure to spironolactone administration predicts the postoperative prognosis of hypertension in patient with PA. Long duration of hypertension and involvement of two or more end-organs were poor prognostic factors. Excellent results can be achieved by unilateral adrenalectomy in adrenal cortical adenoma and fair results, in adrenal cortical macronodular hyperplasia.

Adolescent

The effects of hemodilution with polyethylene glycol bovine hemoglobin (PEG-Hb) in a conscious porcine model.

BACKGROUND: Severe hemodilution in large mammals has been used rigorously for the safety and efficacy testing of hemoglobin-based red blood cell substitutes. The effects of hemodilution with polyethylene glycol-modified bovine hemoglobin (PEG-Hb) were investigated in an unanesthetized porcine model. METHODS: Immature Yorkshire cross barrow pigs were subjected to exchange transfusion with PEG-Hb (n = 6) or dextran 70 (n = 4) until an 80% reduction in hematocrit was achieved. RESULTS: All six (100%) PEG-Hb-infused pigs and only one (25%) dextran 70 control pig survived the resultant reduction in erythrocytes. Heart rates and mean arterial pressure were not significantly affected by PEG-Hb infusion. Pigs infused with PEG-Hb maintained normal levels of blood pH, PO2, and PCO2 while dextran 70 controls showed low PvO2, PaCO2, and the development of acidosis. Histological evaluation revealed that the surviving dextran 70 control animal exhibited possible anoxia-induced hepatic centrilobular necrosis. PEG-Hb-treated pigs demonstrated the presence of renal tubular cell cytoplasmic vacuoles and vacuolated macrophages in spleens. CONCLUSIONS: The results indicate that PEG-Hb effectively supports life close to lethal levels of anemia.

Animals

Lovastatin lowers serum cholesterol levels in non-insulin-dependent diabetes mellitus patients without altering their insulin sensitivity.

BACKGROUND: Lovastatin, a potent 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, has been widely used in the treatment of hypercholesterolemia. It is also applied to dyslipidemia in patients with diabetes mellitus. The influence of lovastatin on insulin sensitivity was evaluated in twelve Chinese non-insulin-dependent diabetes mellitus (NIDDM) patients with hypercholesterolemia. METHODS: This double-blind, randomized, placebo-controlled, and two-period cross-over experiment enrolled 12 patients. After a run-in period of two months, the patients were randomized into 2 groups to receive either lovastatin (20 mg once daily) or placebo treatment. Eight weeks later, two groups of patients exchanged their treatment for another 8 weeks. Blood samples were collected at the end of the run-in period and at 4-week intervals during the study to observe serum lipid profiles. A modified insulin suppression test was made to assess insulin sensitivity three times: at the end of run-in period, in week 8 and week 16, respectively. Wilcoxon signed rank test was used for analysis of statistical significance of the difference between lovastatin and placebo treatments. RESULTS: As compared with the placebo, lovastatin reduced serum total cholesterol (TC) levels significantly. Serum total triglyceride (TG) concentrations decreased slightly by lovastatin. The ratio of TC to high density lipoprotein-cholesterol (HDL-C) also decreased significantly in lovastatin period. No difference was found in serum apolipoprotein A1 levels. A significant reduction of serum apolipoprotein B concentrations was also noted in lovastatin period. No difference in glycemic indices and insulin sensitivity was observed in the base-line, placebo or lovastatin periods. CONCLUSIONS: The results demonstrated that lovastatin significantly lowered the serum TC levels without perturbation of insulin sensitivity in hypercholesterolemic NIDDM patients.

Aged

Changes of propofol levels in isolated cardiopulmonary bypass circuit.

BACKGROUND: High dose fentanyl anesthesia in cardiac surgery has been supplemented with propofol to prevent patient's awareness and recall. It has been known that during cardiopulmonary bypass (CPB), fentanyl or midazolam concentration decreases, except for propofol where it remains unknown. This study evaluated the interaction between propofol and the CPB circuit in vitro. METHODS: Three identical experiments were conducted. In each experiment we used a set of CPB circuit composed of a standard 3/8 inch PVC tubing trap, a reservoir and a pump. The reservoir was primed with 2,000 ml solution of 2.5% dextrose and 0.45% NaCl in which 20 mg propofol was added. The solution was circulated in the circuit at a flow rate of 2 L/min. The experimental period was 30 min. A 5 ml sample of the solution was taken from the venous sampling site of the circuit immediately prior to the experiment, and thereafter each from the arterial and venous sampling sites at 1, 3, 5, 10, 20 and 30 min after the start of the experiment. The samples were kept at 4 degrees C and assayed by HPLC. RESULTS: The propofol concentrations decreased exponentially with the increase of experimental time. There were no significant differences in the concentrations and the rates of decrease between the arterial sampling site and the venous sampling site. The decrease was 20% at 1 min, 68% at 10 min, 83% at 20 min, and 92% at 30 min after the beginning of the experiment. CONCLUSIONS: The results demonstrate the presence of propofol sequestration by the CPB circuit. Evaporation in the bubble oxygenator, absorption by and/or adherence to the circuit are suspected as the possible causative factors.

Anesthetics, Intravenous