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Biomedical subjects

C K Chan

Publications and source records attributed to C K Chan.

At least 199 records · Page 11Linked to original sources
PubMed1990

Actin assembly in electropermeabilized neutrophils: role of intracellular calcium.

Assembly of microfilaments involves the conversion of actin from the monomeric (G) to the filamentous (F) form. The exact sequence of events responsible for this conversion is yet to be defined and, in particular, the role of calcium remains unclear. Intact and electropermeabilized human neutrophils were used to assess more directly the role of cytosolic calcium [( Ca2+]i) in actin assembly. Staining with 7-nitrobenz-2-oxa-1,3-diazole-phallacidin and right angle light scattering were used to monitor the formation of F-actin. Though addition of Ca2+ ionophores can be known to induce actin assembly, the following observations suggest that an increased [Ca2+]i is not directly responsible for receptor-induced actin polymerization: (a) intact cells in Ca2(+)-free medium, depleted of internal Ca2+ by addition of ionophore, responded to the formyl peptide fMLP with actin assembly despite the absence of changes in [Ca2+]i, assessed with Indo-1; (b) fMLP induced a significant increase in F-actin content in permeabilized cells equilibrated with medium containing 0.1 microM free Ca2+, buffered with up to 10 mM EGTA; (c) increasing [Ca2+]i beyond the resting level by direct addition of CaCl2 to permeabilized cells resulted in actin disassembly. Conversely, lowering [Ca2+]i resulted in spontaneous actin assembly. To reconcile these findings with the actin-polymerizing effects of Ca2+ ionophores, we investigated whether A23187 and ionomycin induced actin assembly by a mechanism independent of, or secondary to the increase in [Ca2+]i. We found that the ionophore-induced actin assembly was completely inhibited by the leukotriene B4 (LTB4) antagonist LY-223982, implying that the ionophore effect was secondary to LTB4 formation, possibly by stimulation of phospholipase A2. We conclude that actin assembly is not mediated by an increase in [Ca2+]i, but rather that elevated [Ca2+]i facilitates actin disassembly, an effect possibly mediated by Ca2(+)-sensitive actin filament-severing proteins such as gelsolin. Sequential actin assembly and disassembly may be necessary for functions such as chemotaxis.

Actins↗
PubMed1990

Defective fasciculata zone function as the mechanism of glucocorticoid-remediable aldosteronism.

Glucocorticoid-remediable aldosteronism is characterized by unusual sensitivity of aldosterone secretion to ACTH. Suppressibility by glucocorticoid and continued stimulability by exogenous ACTH has provided the basis for diagnosis and treatment of the disorder. A qualitative biochemical abnormality consisting of marked overproduction of the products of the cortisol C-18 oxidation pathway, 18-hydroxycortisol and 18-oxocortisol, has been examined in 10 patients with the disorder and compared to the normal C-18 oxidation products of corticosterone, aldosterone, and 18-hydroxycorticosterone. The technique, based on stable isotope dilution mass fragmentography, measured the tetrahydro urinary metabolites of aldosterone, 18-hydroxycorticosterone, and 18-oxocortisol and unmetabolized 18-hydroxycortisol. All 4 C-18 oxygenated corticosteroids were markedly elevated in the untreated state and showed rapid parallel suppression with low doses of glucocorticoid. The proportional changes in C-18 oxygenated cortisols together with aldosterone and 18-hydroxycorticosterone suggested the mechanism of a common catalytic site of a cytochrome P450 methyl oxidase serving both cortisol and corticosterone substrates. The ACTH-dependent secretion of the C-18 oxidation products of both corticosterone and cortisol in the disorder is attributed to the acquisition of methyl oxidase activity by the fasciculata zone, where there are abundant pools of these precursors.

Adolescent↗
PubMed1990

Cytomegalovirus pneumonia in allogeneic bone marrow transplantation. An immunopathologic process?

Recent literature suggests that CMV pneumonia is an immunopathologic process. This case report summarizes the clinical course of a patient which supports this hypothesis. The patient is the recipient of an allogeneic BMT who recovered from an episode of CMV pneumonia that occurred about two months after the transplant. Despite recovery from the viral infection, follow-up BALs revealed persistent lymphocytosis in an apparent asymptomatic patient. He subsequently developed BOOP about four months after the initial CMV infection. These observations suggest that the viral infection may have resulted in the activation of the host's cell-mediated response and provides evidence to support the hypothesis that CMV pneumonia is an immune-mediated process.

Adult↗
PubMed1990

The malignancy-sarcoidosis syndrome.

In a retrospective review of six patients with malignancy preceding sarcoidosis, we found four cases of malignant lymphoproliferative disease (LD) and one case each of ovarian cancer and breast cancer. The median interval from onset or relapse of malignancy to sarcoidosis was nine months. Of the four patients with LD, sarcoidosis appeared within six months of termination of chemotherapy for three of the patients and 15 months after allogeneic bone marrow transplantation for the fourth patient. At the time of diagnosis of sarcoidosis, there was no clinical or pathologic evidence of malignancy in the chest. We conclude that in contradistinction to the previously described syndrome of sarcoidosis preceding LD, there exists a syndrome of sarcoidosis following malignancy with or without chemotherapy.

Adult↗
PubMed1990

Pulmonary complications following bone marrow transplantation.

Pulmonary complications are a common cause of morbidity and mortality after bone marrow transplantation. Some of these complications are infectious and related to the degree of ongoing immunosuppression, and thus vary with the posttransplant marrow reconstitution and the need for continued immunomodulating drugs. Noninfectious complications are related to previous chemotherapy, the transplantation protocol and conditioning regimen, and, in allogeneic transplants, the presence of graft-versus-host disease. The various complications are classified based on their timing after the transplant procedure. A diagnostic and therapeutic approach is outlined and the prognosis is discussed.

Bone Marrow Transplantation↗
PubMed1989

Actin assembly in electropermeabilized neutrophils: role of G-proteins.

Polymerization of microfilaments, one of the responses triggered in neutrophils by stimuli such as the chemoattractant N-formyl-methionyl-leucyl-phenylalanine (fMLP), involves the conversion of actin from the monomeric to the filamentous form. The exact sequence of events responsible for this conversion remains to be defined, but its susceptibility to inhibition by pertussis toxin provides indirect evidence that GTP-binding proteins (G-proteins) are involved. In this report, electropermeabilized cells were used to obtain more direct evidence of a role for G-proteins in actin assembly. Staining with 7-nitrobenz-2-oxa-1,3-diazole (NBD)-phallacidin and flow cytometry were used to monitor the formation of filamentous actin. GTP-gamma-S, a nonhydrolyzable analogue of GTP and aluminum fluoride, which in combination with GDP can activate G-proteins, stimulated actin assembly in electropermeabilized cells but had only marginal effects on intact cells. fMLP-induced actin polymerization in permeabilized cells was inhibited by pretreatment with GDP-beta-S, an analogue of GDP that stabilizes the inactive form of G-proteins. In contrast, stimulation by phorbol 12-myristate 13-acetate (PMA) was largely unaffected by GDP-3-S. These observations indicate that activation of G-proteins is essential for actin assembly induced by receptor-dependent stimuli such as fMLP. Moreover, GTP-binding proteins do not seem to be required in the late stages of the signalling cascade, i.e. after stimulation of protein kinase C.

Actin Cytoskeleton↗
PubMed1989

Anomalous oxidative cleavage of the side chain of 18-oxocortisol and its tetrahydro metabolite.

The course of oxidative side chain cleavage of two recently isolated 17 alpha-hydroxy C-18 oxygenated naturally-occurring corticosteroids differed in that 18-hydroxycortisol yielded a 17-ketosteroid (Chu M. D., and Ulick S. (1982) J. biol. Chem. 257, 2218-2224) whereas 18-oxocortisol yielded a gamma-etiolactone (Ulick S., Chu M. D. and Land M. (1983) J. biol. Chem. 258, 5498-5502). In an analytic application of the periodic acid oxidative cleavage reaction to 18-oxocortisol, the finding of a second product of the reaction prompted a reinvestigation of its course. Both the delta 4,3-ketone secreted form of the steroid and its tetrahydro urinary metabolite were cleaved predominantly to 17-ketosteroids along with smaller amounts of gamma-etiolactones, whose proof of structure is herein reported. This anomalous course of oxidative cleavage was considered to reflect an equilibrium between C-20 ketone and cyclic-hemiketal forms in which the glycerol-type side chain structure of the later becomes the precursor of a 17-ketosteroid. Because of the similarities between in vitro oxidative side chain cleavage and in vivo corticosteroid metabolism, these findings suggest that C-18 oxygenated steroids may contribute to the 17-ketosteroid fraction of human urine.

Gas Chromatography-Mass Spectrometry↗
PubMed1989

A new form of the syndrome of apparent mineralocorticoid excess.

The syndrome of apparent mineralocorticoid excess combines the features of unexplained but spironolactone-correctable mineralocorticoid excess in association with a decreased rate of oxidation of cortisol to cortisone. No relationship was initially implied between the pathogenesis of the disorder and the metabolic disturbance as expressed by an elevated cortisol:cortisone metabolite ratio but the ratio itself has served as a biochemical marker for the disorder. Cortisol has been suggested as the mineralocorticoid in a setting of enhanced sensitivity to the steroid as a result of the incomplete oxidative metabolism of cortisol by the kidney. We present evidence that diminished conversion of cortisol to cortisone is not an obligatory mechanism in the syndrome of apparent mineralocorticoid excess. A form of the disorder is described, designated the Type 2 variant, in which all features are preserved except that the cortisol:cortisone metabolite ratio is normal. An essential feature of both variants, however, is a decrease in the cortisol metabolic clearance rate. These findings require a more generalized definition of the syndrome of apparent mineralocorticoid excess to include other deficient mechanisms of metabolic inactivation of cortisol.

Adolescent↗
PubMed1989

Delayed subretinal fluid absorption after pneumatic retinopexy.

Eight of 38 eyes consecutively treated with pneumatic retinopexy were found to have delayed subretinal fluid absorption (DSRFA). In six of eight eyes, a shallow pocket of loculated fluid developed with small subretinal pigment precipitates, possibly a unique feature associated with pneumatic retinopexy. Although loculated DSRFA may not affect the anatomic success, poor visual outcome can result if the macula is involved (4 eyes). Loculated submacular DSRFA may cause bothersome postoperative symptoms, because its resolution may be prolonged for months. Factors found significantly associated with DSRFA were subretinal precipitates and heavy cryotherapy. Demarcation lines, dependent subretinal fluid by the macula, long duration of detachment, and phakic status were factors more frequently found in eyes with than without DSRFA, although the correlations lacked statistical significance. A detailed description of loculated DSRFA after pneumatic retinopexy not found in the literature is presented.

Absorption↗
PubMed1989

An analysis of gastric and oesophageal cancers found with 'epidemiological necropsy' during 1953-1982.

The 'epidemiological necropsy' is a newly proposed research strategy in which the size and composition of the epidemiological reservoir of undetected disease is estimated from the relative frequency of necropsy surprise patients, in whom the disease was not suspected during life. The current study was done to help validate a basic premise of the strategy. We examined the surprise necropsy discovery of two upper gastrointestinal malignancies: oesophageal cancer, for which an undetected reservoir would not be expected because the cancer has little room to grow, and gastric cancer, for which a sizeable reservoir might be anticipated. In a review of 15,812 necropsies during 1953-1982 at Yale-New Haven Hospital, 70 cases of oesophageal cancer were identified postmortem. Except for five surprise cases, located at the gastro-oesophageal junction where there is room to grow, no oesophageal cancer reservoir was found during the 30-year period. In the same secular period, however, a distinctive set of reservoir cases was found among 162 necropsy instances of gastric cancer. About two-thirds of these gastric cancers had been previously diagnosed during life, but the remainder consisted of either necropsy surprise cases or patients with wrong primary cancer diagnoses during life. The secular rates of occurrence remained stable and similar in both sexes for surprise gastric cancer cases during the three 10-year periods from 1953-1982, but no wrong primary diagnoses occurred during 1978-1982, after the introduction of improved methods of premortem diagnosis. The results help validate the cancer reservoir theory for malignancies that have room to grow, and confirm the concept that the 'epidemiological necropsy' can reflect qualitative and quantitative changes in cancer reservoirs.

Autopsy↗
PubMed1989

More lung cancer but better survival. Implications of secular trends in "necropsy surprise" rates.

In previous research, we have demonstrated the value of using necropsy "surprise" lung cancer cases, in those in whom lung cancer was not suspected during life, to estimate the size and composition of the "reservoir" of undetected lung cancer in the general population. The current research was done to determine the characteristics and consequences of secular changes over time in the composition of the lung cancer "reservoir." The results suggest that further advances in diagnostic technology will enhance detection during life of the large "reservoir" of resectable lung cancer, particularly in women. With the increased detection of these reservoir cases during life, the statistical occurrence rates for lung cancer will seem to increase, but survival rates will seem to improve because more of the detected cases will be resectable.

Autopsy↗
PubMed1989

Phrenic involvement in Charcot-Marie-Tooth disease. A pathologic documentation.

A 69-year-old woman diagnosed as having Charcot-Marie-Tooth disease (CMT) for 30 years' duration died of respiratory failure secondary to diaphragmatic weakness. At autopsy, identical neuropathic changes were found in phrenic and other affected somatic peripheral nerves. We conclude that the phrenic nerve may be involved by the neuropathy of at least some forms of CMT.

Aged↗
PubMed1989

Respiratory muscle weakness in Charcot-Marie-Tooth disease. A field study.

A field study on respiratory muscle function and basic pulmonary mechanics was conducted at an international convention of 200 individuals with Charcot-Marie-Tooth disease. Forty patients with respiratory symptoms were evaluated; 15 had significant respiratory muscle dysfunction and 25 were normal. The results suggest that proximal upper limb involvement in individuals with Charcot-Marie-Tooth disease is a simple but significant predictor of respiratory muscle dysfunction.

Adolescent↗
PubMed1988

Myelin basic protein binds GTP at a single site in the N-terminus.

Myelin basic protein from normal human brain was ADP-ribosylated with Cholera toxin, but not with Pertussis toxin. It bound azido-GTP at a single site in the N-terminal tetrapeptide at the Gln residue. The binding was considerably reduced when GppNHp was present during azido-GTP binding and totally inhibited when GTP gamma S was present. The relevance of this specific binding is not understood at this time.

Adenosine Diphosphate Ribose↗
PubMed1988

The value and hazards of standardization in clinical epidemiologic research.

The statistical standardization of rates produces a single summary value that converts crude rates of occurrence into "standardized" rates that are adjusted for differences in the composition of compared populations. Although the process is well described in the epidemiologic literature and is regularly applied in comparisons of large populations, many investigators are not familiar with three important hazards that are magnified for the smaller groups studied in clinical epidemiologic research. This report contains a new "symmetrical" outline of the direct and indirect standardization processes, and an illustration of three pragmatic hazards: (1) Because the direct standardizing factor uses the observed stratum-specific rates, and because any stratum-specific rates that depend on small denominators may be misleading or unstable, the indirect method is preferred when the observed strata have small denominators. (2) Both the direct and indirect standardizing methods are highly vulnerable both to the choice of reference population and to the boundaries chosen when strata are demarcated or consolidated. The standardized rates can be altered dramatically according to differences in the stratum proportions of the reference population, or to distinctions produced when standardizing strata are consolidated. (3) If the stratum-specific rates and stratum proportions have different patterns of variation across the strata of the compared groups, the use of a single summary value--no matter what method of standardization is applied--may obscure cogent patterns of variation and significant differences in the stratum-specific rates. These hazards can be overcome if the studied group and the reference population are carefully compared for inconsistent variations in the stratum-specific rates and proportions before any standardizing procedure is applied. In many instances, the best approach may be to compare the unaltered stratum-specific rates, without standardization.

Adult↗