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Biomedical subjects

C L Lau

Publications and source records attributed to C L Lau.

28 records · Page 2Linked to original sources

Lung transplantation at Duke University Medical Center.

Lung transplantation is a viable therapy for patients with a variety of end-stage lung diseases. Our active program now includes over 200 lung transplant operations with acceptable one- and 3-year survival rates of 78% and 61%. A major focus of clinical research at this institution is to design strategies to prevent the development of chronic allograft dysfunction. Our preliminary work in this regard has been encouraging. In addition, a major research focus has been to design protocols to prevent the development of posttransplant infections. Our work with aerosolized ABLC represents a major advance at our center, and additional randomized prospective studies are ongoing to define the optimal antifungal prophylaxis after transplantation. Ongoing clinical and basic research at Duke and elsewhere should continue to advance the field of clinical transplantation and ultimately lead to more acceptable long-term outcomes for lung allograft recipients.

Adult↗

Identification of two types of smooth muscle cells from rabbit urinary bladder.

Cells from the muscular layer of neonatal (3-day-old) rabbit urinary bladders were dissociated with collagenase, and cultured in M199 supplemented with 10% fetal bovine serum and antibiotic-antimycotic. Cells in culture were of two types: long and short. The short cells were thick and spindle-shaped, and the long cells were flat and elongated. The long cells can be about 15 times longer than the short cells. The short cells do not divide, but the long cells divide readily. Expressions of smooth muscle and non-muscle myosins, alpha-smooth muscle actin, vimentin, and h-caldesmon were determined by immuno-fluorescence microscopy using specific antibodies. Both types of cells react strongly with antibodies against smooth and non-muscle myosins. Unlike the short cells, the long cells also contain alpha-actin and vimentin. The expression of h-caldesmon was very weak in both cell types. Also, cells dissociated from the smooth muscle layers of adult (6-month-old) rabbit bladder were cultured under the same conditions as the cells from the neonatal bladders to see if the heterogeneity of smooth muscle cells, exhibited by cells from neonatal rabbits, is also shown by cells from adult bladder. Two types of cells were also identified. The cells were then fixed and examined with the same panel of antibodies that we used for the neonatal cells. The long cells from adult bladder muscle express similar proteins to those in the neonatal long cells, and the short cells were stained positively with smooth muscle myosin, non-muscle myosin, alpha-smooth muscle actin, and lightly with caldesmon. Although the absence of vimentin in the short cells from adults is similar to that from neonatal, the strong expression of alpha-actin in the adult short cells is unlike the short cells from neonatal rabbits, in which their expression is barely detectable.

Actins↗

Analysis of tissue organization by microinjection of follistatin into early Xenopus laevis embryos.

Xenopus laevis embryos injected with follistatin developed abnormally with enlarged anterior structures and defective tails. Histological sections reveal that these follistatin treated embryos contain large amount of notochordal tissue that fails to elongate. Embryonic responses to follistatin are dose and stage specific. These results suggested that follistatin contributes to body axis formation, with its most visible effect on notochord formation.

Animals↗

Behavior of embryonic chick heart cells in culture. 3. Spatial distribution of epidermal growth factor in heart muscle cells.

Muscle cell-enriched primary cell cultures were prepared from 8-day embryonic chick heart ventricles. Immunostaining with an anti-EGF antibody detected the presence of EGF in the heart muscle cells, in a perinuclear distribution. In addition, some of the EGF appeared to be associated with the sarcomeres. Moreover, immunostaining with an anti-EGF receptor antibody also detected perinuclear localization, albeit not among the sarcomeres. Previous studies have shown that the heart muscle and non-muscle cells in culture respond to EGF to increase [3H]thymidine incorporation and cell division (Lau, 1993b). These data suggest the roles of EGF as a natural regulator in the development of the embryonic chick heart.

Animals↗

Behavior of embryonic chick heart cells in culture. 1. Cellular responses to insulin-transferrin-selenium.

Muscle cell-enriched primary cell cultures were prepared from 8-day embryonic chick heart ventricles (74% of these cells showed positive staining with anti-cardiac myosin antibody). To determine if ITS (a commercial mixture of insulin, transferrin, and selenium) affects these cardiac muscle cells, immunostaining and autoradiography were performed to determine the Muscle Cell Labeling Index (MLI). MLI represents the proportion of cardiac myosin-positive cells that specifically incorporated [3H]thymidine. The MLI for ITS-treated cells was 52%. Controls in Serum-free Nutrient Medium (SFNM) had a MLI of 27%. Combinations of growth signals also were tested. Whereas 5% Fetal Bovine Serum (FBS) was optimal for stimulation of [3H]thymidine incorporation, 10 and 20% FBS elicited an inhibitory effect. Addition of ITS enhanced the stimulatory effect of FBS and relieved some of the inhibitory effect. TGF-beta also was shown to have inhibitory effect on [3H]thymidine incorporation in these heart cells, but the inhibitory effect was not seen when it was added with ITS. Staining with anti-cardiac myosin antibody revealed that when the cells were cultured with ITS for 6 or 10 days, the percentages of muscle cells were 65 and 59%, whereas the percentages of muscle cells of controls in SFNM dropped to 44 and 31% respectively. Additional experiments showed that cell number increased in the presence of 5% FBS. In contrast, although ITS stimulated DNA synthesis, it did not immediately stimulate complete cell division. The percentage of muscle cells remained around 74% in the presence of 5% FBS, whereas it fell slightly (to 65%) in SFNM. This study showed that cardiac muscle cells from 8-day embryos in culture were responsive to ITS, FBS and TGF-beta and that ITS may be permissive for continued expression of differentiation of embryonic cardiac muscle cells.

Animals↗

Behavior of embryonic chick heart cells in culture. 2. Cellular responses to epidermal growth factor and other growth signals.

Muscle cell-enriched primary cell cultures were prepared from 8-day embryonic chick heart ventricles (74% of these cells showed positive staining with anti-cardiac myosin antibody). To determine if Epidermal Growth Factor (EGF) affects cardiac muscle cells, immunostaining and autoradiography were performed to find the Muscle Cell Labeling Index (MLI). MLI represents the proportion of cardiac myosin-positive cells that specifically incorporated [3H]thymidine. The MLI for EGF-treated cells was 51%. Controls in Serum-free Nutrient Medium (SFNM) had a MLI of 34.5%. Combinations of growth signals also were tested. EGF, IGF-I (Insulin-like Growth Factor-I), or PDGF (Platelet-derived Growth Factor) alone increased [3H]thymidine incorporation in the cells. Adding IGF-I or PDGF simultaneously with EGF enhanced the response of the cells to EGF by increasing [3H]thymidine incorporation. TGF-beta (Transforming Growth Factor-beta) alone was shown to have an inhibitory effect on [3H]thymidine incorporation, and when TGF-beta was added together with EGF, it attenuated the stimulatory effect of EGF on [3H]thymidine incorporation. Phorbol 12-Myristate 13-Acetate (PMA), a tumor promoter, alone had no effect on [3H]thymidine incorporation, but its addition suppressed the stimulatory effect of EGF when they were added simultaneously in the presence of 5% FBS. Developmental response of the heart cells to growth signals also was tested. Heart cells from 18-day embryos were used to test the effect of insulin and EGF. Although both insulin and EGF increased [3H]thymidine incorporation in heart cells from 8-day embryos, different responses to insulin and EGF occurred with heart cells from 18-day embryos. Whereas the heart cells from 18-day embryos still responded to EGF by increasing [3H]thymidine incorporation, they did not show a response to insulin as measured by [3H]thymidine incorporation, suggesting that the loss of response of the heart cells to growth signals may occur at the receptor level. Further studies show that EGF, TGF-alpha, aFGF, and PDGF increased the total numbers of heart cells, and that aFGF and PDGF also increased the percentages of heart muscle cells.

Animals↗

Synergistic interaction of D1 and D2 dopamine receptors in the modulation of the reinforcing effect of brain stimulation.

Rats were trained to press a bar for hypothalamic stimulation, and a frequency-response function was plotted. Quinpirole (a selective D2 agonist) facilitated self-stimulation when injected alone but failed to show the facilitatory effect when injected either 1 hr before or 1 hr after injection of SCH 23390 (a D1 antagonist). Injection of reserpine followed by alpha-methyl-p-tyrosine virtually eliminated self-stimulation. Subsequent injection of either SKF 38393 (a D1 agonist) alone or quinpirole alone did not restore self-stimulation, but a combination of quinpirole and SKF 38393 did. The results suggest that a D2 dopamine agonist facilitates the reinforcing effect of brain stimulation only if D1 receptors are activated by endogenous dopamine or by an exogenous agonist.

Animals↗

Screening for psychiatric illness in patients with oral dysesthesia by means of the General Health Questionnaire--twenty-eight item version (GHQ-28) and the Irritability, Depression and Anxiety Scale (IDA).

Thirty-one consecutive subjects suffering from oral dysesthesia and without detectable organic disease were seen in a university outpatient dental clinic. They were assessed with a screening test for psychiatric illness, the General Health Questionnaire, 28-item version (GHQ-28). Twelve subjects also completed the Irritability, Depression and Anxiety Scale (IDA). At the 4/5 cutoff on the GHQ, 51.9% of the patients showed evidence of psychiatric illness. The IDA appeared to be more sensitive than the GHQ-28 in terms of detecting psychiatric illness, especially depression, and 75% of the 12 subjects who completed both scales were found to be depressed on the IDA. These results were compared to results obtained by another cross-sectional study of different types of pain clinics in which the same scales were used to screen for psychiatric illness. The subjects with oral dysesthesia as measured by the IDA appeared to have psychiatric illness more often than the other subjects with chronic pain, except those attending a psychiatric clinic. The GHQ-28 results on the other hand showed less psychiatric illness in the latter group. Our findings indicate that psychiatric illness, especially depression, may play an important role in this disorder and that the IDA may be more sensitive than the GHQ for detecting depression.

Adult↗

The relationship between pain drawings and the psychological state.

Pain patients may be requested to complete pain charts as part of their evaluation at pain clinics. Inferences are made about the 'psychological content' of the patient's pain on the basis of the extent and distribution of the pain as illustrated in these drawings. In this study, the records of 328 patients from 4 distinct types of chronic pain service, were scored for how many body parts were included in the pain drawings and the percentage of body surface area involved. Four psychological instruments were used to quantify the psychological status of the patients. These included 2 measures of current psychological status (the General Health Questionnaire-28, and the Irritability/Depression and Anxiety Questionnaire), 1 measure of childhood quality (the Parental Bonding Index), and 1 measure of premorbid personality (the Hysteroid/Obsessoid Questionnaire). No significant correlation was found between the percentage of body surface area affected by pain, and the measures of childhood quality. Only very limited correlations were found between the percentage of the body surface area with pain and the measures of current psychological state and premorbid personality. Hence, strong emphasis should not be placed on the involvement of multiple areas as a sign of psychological illness.

Chronic Disease↗

Screening for psychiatric morbidity. The pattern of psychological illness and premorbid characteristics in four chronic pain populations.

Three hundred and seventy-eight patients from 4 chronic pain populations have been examined by self-assessment questionnaire methods to estimate the amount of psychiatric morbidity present. Using the General Health Questionnaire-28 scaled version (GHQ-28) the findings for probable psychiatric illness by clinic were: for anaesthetists' pain clinics serving a mixed urban and rural population--37%; for an oral medicine facial pain clinic--30%; for a rural hospital pain clinic--37%; and for a psychiatrists' pain assessment and treatment service--51%. These findings demonstrate the effects of selection upon the psychiatric characteristics of different pain populations. On the subscales of the General Health Questionnaire the psychiatric clinic patients were significantly more depressed than those in the other 3 groups (P less than 0.001) and also showed more social dysfunction (P less than 0.001). On the Irritability/Depression and Anxiety Questionnaire (IDA), depression and inward irritability were higher in the psychiatric clinic patients (P less than 0.001) but the amount of anxiety did not differ by clinic or by diagnosis (P greater than 0.05). These findings are taken to indicate that the extent of somatic complaints and anxiety does not differentiate the majority of pain patients in pain services with psychological illness from others attending for treatment. However, in the patients who have definite psychological symptoms, depression, social dysfunction and irritability provide a characteristic pattern. The psychiatric clinic patients were demonstrably more introverted or obessional on the Hysteroid/Obsessoid Questionnaire (HOQ) than those in other clinics. Childhood experience as seen by the patients did not differ by clinic or diagnosis and did not correlate significantly with personality as measured by the HOQ. It did correlate very significantly with measures of the current mood represented by the IDA. This effect was relatively weak, permitting the inference that the major portion of those psychological abnormalities which were found to be present was related to other factors such as the occurrence of painful lesions.

Adult↗