Biomedical subjects
Publications and source records attributed to C M Lee.
A 32 year old patient with end-stage cardiomyopathy underwent heterotopic heart transplantation with a small donor heart. Monitoring of this unusual clinical setting of two hearts beating independently in one chest required special technique and scrutinous interpretation so one can differentiate donor heart from recipient heart immediately.
A nephritic condition was developed by infecting Swiss Webster albino mice with the malarial parasite Plasmodium berghei NK 65. These animals were tested for urinary protein and the presence of circulating immune complexes using reagent strips and a polyethylene glycol (PEG) precipitation assay. The circulating immune complexes were isolated from the sera using both affinity chromatography and PEG precipitation and from the kidney by acid elution. The isolated complexes were dissociated into their individual components and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The components of the complexes were transferred to nitrocellulose sheets and probed for the presence of malarial antigens using a rabbit anti-P berghei antisera. The overall humoral response to the malarial parasite was evaluated using a radial immunodiffusion assay. The present study confirmed that the malarial-infected animals not only developed the nephritic condition (as evident by the high levels of proteinuria) but also, as indicated by the PEG assay, have the presence of high levels of circulating immune complexes in their serum. The apparent absence in the SDS gels of any abnormal protein bands followed by the inability of the Western blot to reveal any malarial antigens provides some of the strongest evidence to date that these malarial proteins are not directly involved in the circulating immune complexes believed to be responsible for producing this nephritic condition.
We have previously shown that activation of the phosphatidyl-inositol/phospholipase C pathway could induce interleukin 6 (IL-6) release from U373MG human astrocytomes cells. We also found that, although interleukin 1 beta (IL-1 beta) did not activate phosphatidy-linositol turnover, it induced, a robust release of IL-6. In the present study, we examined the role of adenylate cyclase/cyclic 3',5'-adenosine monophosphate (cAMP) pathway in IL-6 release. Agents which mimicked (dibutyryl cAMP) or stimulated (isoproterenol and forskolin) cAMP formation were found to induce IL-6 release and their effects could be potentiated by 3-isobutyl-1-methylxanthine (IBMX), a phosphodiesterase inhibitor. On the other hand, in spite of its robust action on IL-6 release, IL-1 beta did not stimulate cAMP formation. Other possible signal transduction mechanisms involved in IL-1 beta-induced IL-6 release are discussed.
The tendency of both labeled and unlabeled beta-amyloid to bind in solution to C1q, the recognition species in the complement cascade, was examined using both hydrodynamic and spectroscopic methods. Potential binding interactions were evaluated using a purified synthetic beta-amyloid 1-40 sequence, alone, and selectively labeled at the amino terminus with spectroscopic probes. The probes permitted both absorbance and fluorescence analyses of beta-amyloid binding interactions. Under conditions used for the analyses beta-amyloid exists exclusively as a monomer in solution, and C1q retains an intact quaternary structure and is capable of binding to IgM. When mixed together the monomeric beta-amyloid does not bind to, or interact with, the complement C1q at concentrations below approximately 100 microM. The data suggest that if beta-amyloid toxicity is associated with complement activation in Alzheimer's disease then monomeric beta-amyloid is likely not responsible for activation through the classical complement pathway.
Helicobacter pylori was found to be a promoter factor of peptic ulcer that has an incidence higher in patients with hepatic cirrhosis. To clarify the role between H. pylori and peptic ulcer in patients with hepatic cirrhosis, a serological test (ELISA test, HEL-p, AMRAD, Australia), was used to measure the presence of H. pylori of patients with hepatic cirrhosis. Within two years, 108 cirrhotic patients who had received a panendoscopic examination were enrolled in this study. There were 79 males and 27 females with a mean age of 53.2 years. Sixty-four cases had positive serum HBsAg and 44 had negative serum. The results showed that the prevalence of Helicobacter pylori in cirrhosis was 43.5% (47/108). There was no difference of HEL-p-positive rate between peptic ulcer and normal gastroduodenal mucosa (45.2% vs 46.1%, P > 0.05). According to this study, there appears to be no relation between peptic ulcer and H. pylori in patients with hepatic cirrhosis. The etiology of peptic ulcer in cirrhotic patients need further study.
OBJECTIVE: An abnormal umbilical artery Doppler waveform is a risk factor for adverse perinatal outcome. However, it has not been established whether this is related to the earlier gestational age at delivery of fetuses with abnormal Doppler findings or whether Doppler findings are an independent predictor of perinatal outcome. Our purpose was to determine whether an abnormal Doppler umbilical artery waveform is associated with adverse perinatal outcome even after the gestational age at delivery is controlled for as a confounding variable in patients with preeclampsia. STUDY DESIGN: Umbilical artery velocimetry studies were performed within 7 days of delivery in 72 consecutive patients admitted to our unit with preeclampsia. Adverse perinatal outcome was defined as fetal distress requiring cesarean delivery. Apgar score < 7 at 5 minutes, significant neonatal morbidity, or perinatal death. Significant neonatal morbidity was defined as neonatal sepsis, intraventricular hemorrhage (grade > or = 2), respiratory distress syndrome, pneumonia, bronchopulmonary dysplasia, acute renal failure, or necrotizing enterocolitis. Stepwise multiple logistic regression and receiver-operator characteristic curve analysis were used. RESULTS: Patients with abnormal umbilical artery velocimetry had a significantly higher rate of complications, including cesarean section for fetal distress, preterm delivery, low Apgar scores, significant neonatal morbidity, and perinatal death, than did patients with a normal waveform. Receiver-operator characteristic curve and stepwise logistic regression analysis indicated that an abnormal umbilical artery waveform was a significant independent predictor for the development of adverse perinatal outcome (odds ratio 14.2, p < 0.005) after other confounding variables were adjusted. CONCLUSION: An abnormal Doppler umbilical artery waveform is a strong and independent predictor of adverse perinatal outcome in patients with preeclampsia.
The large majority of mitochondrial DNA (mtDNA) deletions analyzed from mitochondrial myopathies and aging humans have been found to be flanked by direct repeats, a finding which has led to the slip-replication hypothesis of deletion formation. In this study, we have characterized 13 mtDNA deletion breakpoints from skeletal muscle harvested from 9- to 27-year-old rhesus monkeys. Seven of the deletions, five of which were unique to a particular animal, did not have direct repeats at the deletion breakpoints. In contrast, two of the three deletions common to several animals had direct repeats flanking the breakpoints. It appears, therefore, that at least two different mechanisms exist by which mtDNA deletions are formed during aging, one requiring and one independent of flanking direct repeats. Furthermore, the species in which mtDNA deletions are detected may determine which mechanism predominates.
We studied the changes in lipid peroxidation and prostanoid metabolism in short-term coronary occlusion-reperfusion in controls and those rabbits (11 in each group) fed a 1% high cholesterol diet with or without 10% fish oil supplementation for one week. Acute coronary occlusion for 10 minutes was induced by ligating the marginal branch of the left circumflex coronary artery. The vessels were then reperfused for 1 hour. The cholesterol and fish oil treated rabbits had the lowest malondialdehyde levels both in the ischemic and non-ischemic (normal) areas, the least increase of malondialdehyde level in the ischemic area, and the highest 6-keto-PGF1 alpha/thromboxane B2 ratio in the non-ischemic area after reperfusion among the 3 groups. These rabbits had the highest myocardial superoxide dismutase levels both in the ischemic and normal areas, and the least decrease of superoxide dismutase level in the ischemic area. These data suggest that rabbits fed a high cholesterol diet with fish oil supplementation had an attenuated lipid peroxidation, which reflected a reduced free radical generation during a short-term coronary occlusion followed by reperfusion.
Recent evidence suggests that the level of interleukin-6 (IL-6) is elevated in Alzheimer's disease (AD) brains. IL-6 is produced by reactive glial cells and could potentially affect neuronal survival. Understanding the biochemical mechanism that regulates the production and release of IL-6 by astrocytic cells may help to identify potential targets for therapeutic intervention in AD. In the present study, glial fibrillary acidic protein-positive human U373MG astrocytoma cells were used as a model of reactive astrocytes. Production of IL-6 in response to drug treatment was monitored with an ELISA assay. Histamine (1-100 microM), substance P (SP; 1-100 nM), and human interleukin-1 beta (IL-1 beta; 1-30 pM) stimulated the release of IL-6 in a time- and concentration-dependent manner, with EC50 values of 4.5 microM, 8 nM, and 4.5 pM, respectively. The respective effects of histamine, SP, and IL-1 beta were effectively blocked by the histamine H1, SP, and IL-1 receptor antagonists, supporting a receptor-mediated event for these agents. Both histamine and SP enhanced the formation of inositol phosphates and increase intracellular calcium levels, suggesting that the phosphatidylinositol bisphosphate/protein kinase C pathway may be involved in the IL-6 release process. Indeed, phorbol 12-myristate 13-acetate, a protein kinase C activator, also evoked IL-6 release from the U373MG cells. On the other hand, IL-1 beta, which produces a much more robust release of IL-6 than histamine or SP, has no effect on inositol phosphate formation or intracellular calcium levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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We have explored the factors that may regulate membrane permeability in a cell line (NCL-SG3) derived from the human sweat gland epithelium. Ionomycin increased the rate of 125I-efflux from preloaded cells and this action appeared to be due to an increase in intracellular free calcium ([Ca2+]i). The ionomycin-evoked increase in 125I- efflux was reduced in cells that were exposed either to barium or to valinomycin in the presence of a high concentration of external potassium. It thus appears that a fraction of the ionomycin-evoked increase in 125I- efflux is due to the activation of potassium channels and experiments using 86Rb+ also suggested that ionomycin increased the rate of potassium efflux, an effect which was totally abolished by barium. Blockade of Na(+)-K(+)-2Cl- cotransport and of Cl- -HCO3- exchange reduced the basal rate of 125I- efflux and the ionomycin-evoked increase in 125I-efflux from control cells and from cells depolarized by valinomycin. These transport systems thus contribute to anion efflux, although [Ca2+]i-dependent chloride channels also appear to be present. Acetylcholine increases [Ca2+]i in the secretory cells of human sweat glands, but this neurotransmitter did not increase [Ca2+]i in NCL-SG3 cells and so membrane permeability was not under cholinergic control. Adrenaline did not increase [Ca2+]i, but this hormone did evoke cyclic-3',5'-adenosine monophosphate (cyclic AMP) production. However, membrane permeability was not under adrenergic control, as the cells did not appear to express functional, cyclic AMP-dependent anion channels. This may be because they were not fully differentiated under the culture conditions. ATP consistently evoked a dose-dependent increase in anion efflux that appeared to be mediated by [Ca2+]i. The increase in [Ca2+]i was initiated by the release of calcium from a limited internal store and was subsequently sustained by calcium influx. UTP and ADP also increased [Ca2+]i, whereas adenosine, AMP and alpha,beta-methylene ATP were without effect. These data thus suggest that a subclass of type 2 purine receptor, which is functionally coupled to phosphoinositidase C, is present in these cells.
OBJECTIVE: To report our experience of eight patients with primary gastric leiomyosarcoma. DESIGN: Retrospective study. SETTING: Teaching hospital, Taiwan. SUBJECTS: 8 patients who presented with primary gastric leiomyosarcoma between 1986 and 1990. MAIN OUTCOME MEASURES: Endoscopic, radiological, and histopathological features, DNA ploidy, and outcome. RESULTS: Abdominal pain and gastrointestinal bleeding were the most common presenting symptoms. In 5 of the 7 patients who had endoscopy preoperatively a diagnosis of submucosal tumour was made, but a definite diagnosis of leiomyosarcoma was made in only 3. A provisional diagnosis of leiomyosarcoma was made in 3 of the 4 patients who had computed tomography. All patients underwent some form of gastric resection ranging from palliative resection to total gastrectomy. Patients in whom the tumour had invaded adjacent organs had a poor prognosis. Histopathological grading of tumours correlated well with DNA ploidy. CONCLUSION: Both histopathological grading and DNA ploidy could be helpful objective prognostic criteria in patients with primary gastric leiomyosarcoma.
A metabolic imbalance technique was used to study the effects of zinc deficiency on immunoglobulin levels in mice infected with Trypanosoma musculi or immunized with parasite products. Zinc-deficient mice developed higher numbers of parasitemia earlier and exhibited prolonged infection. Irrespective of the diet, higher IgG1, IgG2b, and IgM levels, lower IgG2a and IgA levels, and uniform IgG3 levels were exhibited primarily by mice infected with T musculi and to a lesser extent by mice immunized with parasite products. Zinc-deficient mice showed smaller increases in IgG1 and IgM, but larger gains in IgG2b compared with mice on full-complement and pair-fed diets. However, IgG2a decreased significantly in zinc-deficient mice.
OBJECTIVE: This study assesses the prevalence and characteristics of sexual assault among women patients attending two family medicine residency training clinics. METHODS: Two hundred four consecutive women patients 18 years and older were asked to complete a questionnaire; one hundred eighty-eight (92.2%) agreed. RESULTS: Fifty-four (28.7%) of the 188 women patients reported some type of sexual assault. Approximately 15% of patients reported being victims of rape; 8% reported attempted rape, and 5.3% reported forced sexual contact. Twelve (41.4%) of the 29 rape victims indicated that they had been raped more than once. Only 24% of rape and attempted rape victims reported the incident to police, 18.2% sought medical attention, and 21% sought counseling. CONCLUSIONS: Family physicians should be aware of the prevalence of sexual assault in their practices and should understand proper questioning, management, counseling, and referral of patients.
We compared the outcome of total knee arthroplasty in 19 patients who had had previous patellectomy with the results in a matched series of arthroplasties performed on knees in which the patella was intact. The mean follow-up was 63 months (21 to 114). In the study group, the outcome was poor in five patients. There was instability in the coronal plane in three patients and persistent pain in four. Three supracondylar fractures occurred. The overall complication rate was 36%. In the control group, pain was relieved in every case and there were no complications. Total knee arthroplasty has a higher complication rate and inferior results if the knee has undergone prior patellectomy.
BACKGROUND: This study reports the results of Neodymium-Yttrium-Aluminum Garnet (Nd-YAG) laser resection on benign and malignant obstructing airway diseases which has been done in our hospital for four years. The effect of this treatment on patients' arterial blood gases, during and after the process is also analyzed. The benefit of adjuvant therapy with radiotherapy and/or chemotherapy after laser vaporization is discussed. METHODS: Fiberoptic bronchoscopic Nd-YAG laser therapy was performed in 32 cases of lung cancer (primary 27, secondary 5) and 11 cases of benign tracheobronchial diseases with total or near total airway obstruction. The therapy was performed through the oral route under local anesthesia. The result of therapy was classified as "excellent", "fair" or "poor" depending upon the degree of recanalization and clinical improvement. A cannula was inserted into the radial artery in lung cancer patients before the procedure. Samples of blood to determine arterial blood gas levels were drawn before, during and after treatment. After bronchoscopic laser therapy, radiotherapy and/or chemotherapy were given to the patients of lung cancer. RESULTS: The effective rate (excellent and fair) was 75% in lung cancer and 81.8% in benign airway obstruction. In the lung cancer group, significant decline of PaO2 was noted during and after Nd-YAG laser therapy. Decrease of PaO2 was not recovered even 5 hours after laser vaporization. After bronchoscopic Nd-YAG laser therapy, 21 of 32 lung cancer patients received radiotherapy (at least 3000 rads) and/or chemotherapy (at least 3 times). The median survival time was 5.5 months. The other 11 patients received laser therapy only, with median survival time was 2.9 months (p < 0.05). CONCLUSIONS: Endobronchial Nd-YAG laser therapy of obstructing lesions has been proved to be effective and relatively safe in well-trained hands. Oxygen supplementation was suggested in patients with hypoxemia before laser therapy. After endobronchial Nd-YAG laser therapy, better survival and life quality result if radiotherapy and/or chemotherapy are added for the lung cancer group.
ADP-Ribosylation factors (ARFs) are ubiquitous approximately 20-kDa guanine nucleotide-binding proteins that stimulate cholera toxin-catalyzed ADP-ribosylation in vitro. Because the functional role(s) of ARF in mammalian systems is (are) elusive, we looked for ARF in Drosophila melanogaster, and report the partial purification and molecular cloning of an ARF from Drosophila. We cloned the Drosophila ARF 1 gene without library screening by a combination of 5 polymerase chain reactions (PCRs), yielding a 546-base open reading frame encoding 182 amino acids, which are > 93% identical to those of mammalian class I ARFs. This ARF gene maps to 79F3-6 in the proximal region of the left arm of Drosophila chromosome 3. The Drosophila ARF1 gene structure, including placement of introns, is highly conserved relative to mammalian class 1 ARF genes. A single ARF mRNA species of 1.8 kb was abundant in all Drosophila body segments. Recombinant Drosophila ARF 1 synthesized in Escherichia coli had biochemical and immunochemical activities similar to those of mammalian ARF. The similarities of sequence and biochemical properties between Drosophila and mammalian ARFs contrast with their differences from Drosophila arl (ARF-like protein), which does not stimulate cholera toxin-catalyzed ADP-ribosylation, and is only approximately 52-56% identical in amino acid sequence to mammalian ARFs.
Two heterotrophic denitrifying bacteria, Paracoccus denitrificans and Pseudomonas denitrificans, have been shown to utilize nitric oxide (NO) as a terminal electron acceptor and succinate, yeast extract, and heat/alkali pretreated municipal sewage sludge as carbon and energy sources. Complete removal of NO (0.50%) from a feed gas sparged into the cultures was observed. It is suggested that reduction of NO may be a common feature of denitrifying bacteria and that a microbial process to dispose of NO(x) may be economically viable.