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Biomedical subjects

K K Hui

Publications and source records attributed to K K Hui.

At least 37 records · Page 2Linked to original sources
PubMed1990

Fatal pulmonary failure complicating high-dose cytosine arabinoside therapy in acute leukemia.

One hundred three relapsed leukemia patients were treated with high-dose cytosine arabinoside (Ara-C); 3 g/m2 intravenously over 2 hours every 6 to 12 hours for a total of nine to 12 doses or 3 g/m2 intravenously over 2 hours for two doses 12 hours apart followed by a continuous infusion of 1.5 g/m2 over 24 hours daily for 3 to 4 days. Thirteen of them developed adult respiratory distress syndrome (ARDS) without having any recognized reason for the development of pulmonary edema. This problem showed no correlation with age or prior chemotherapy. Four of the patients recovered, but in nine this complication was fatal. The authors have reviewed the clinical course of these 13 patients and the postmortem findings of the seven patients who had an autopsy performed. The pulmonary tissue from six patients showed massive edema and one had diffuse alveolar damage. Histologic examination revealed a highly proteinaceous intraalveolar infiltrate without any inflammatory reaction in all cases. Intestinal tissue from all patients revealed changes compatible with cytotoxic damage, and pleura and/or pericardium from six of the seven patients showed an extensive fibrinous exudate suggestive of capillary leakage. The time sequence of the clinical events and the histologic findings indicate that high-dose Ara-C treatment in leukemia may cause a capillary leakage syndrome with ARDS that may progress to fatal respiratory failure.

Acute Disease↗
PubMed1990

Protein kinase A and/or C inhibitors potentiate isoproterenol-induced cyclic AMP accumulation in intact human lymphocytes.

The objective of the present study was to investigate the roles of protein kinase A and/or C in agonist-induced beta adrenoceptor activation in intact human lymphocytes. LYmphocytes from healthy subjects were incubated with isoproterenol and phosphodiesterase inhibitor (IBMX, 1.0 mM) after 20 minutes of preincubation with (or without) various compounds possessing protein kinase A and/or C inhibitory activities. These compounds included the relatively selective protein kinase C (PK-C) inhibitors (W-7, calmidazolium, polymyxin B, neomycin, tamoxifen and clomiphene), purified protein inhibitors of protein kinase A (PK-A) (obtained synthetically, or purified from bovine hearts and porcine hearts) and the two compounds (H-7, H-9), which have been found to inhibit both PK-A and PK-C. The results showed that all PK-C inhibitors alone decreased cellular basal cAMP levels while inhibitors of PK-A as well as both H-7 and H-9 increased basal cAMP levels in a dose dependent manner at certain concentrations. All inhibitors studied potentiated isoproterenol-induced cAMP accumulation. The protein kinase A and C inhibitor, H-7, also potentiated PGE1 (but not forskolin)-induced cAMP accumulation. In contrast, the protein kinase C activator, PMA, inhibited isoproterenol- and PGE1- (but not forskolin) induced cAMP accumulation. These data suggest that the potentiating effects of PK-A and/or C inhibitors may be related to the inhibition of PK-A and/or PK-C, both of which have been shown to be involved in beta 2 adrenoceptor desensitization and phosphorylation.

Alprostadil↗
PubMed1990

Undifferentiated carcinomas of the major salivary glands.

Undifferentiated salivary carcinomas are defined as primary epithelial malignant neoplasms that are devoid of any phenotypic expression by light microscopy that would allow them to be otherwise classified. A clinicopathologic study of sixteen so-defined carcinomas of the major salivary glands is presented. The carcinomas are unquestionably high-grade malignant neoplasms. Ten of the sixteen patients were dead because of their disease within 4 1/2 years of histologic diagnosis. Cell size and ultrastructural features have little bearing on prognosis. The single most important clinicopathologic factor relating to patient outcome is size of the primary neoplasm. All patients with carcinomas larger than 4 cm died, and these carcinomas had nearly two times the incidence of perineural invasion, extrasalivary extension, and locoregional failure of control.

Aged↗
PubMed1990

Beta-adrenergic receptors on human lymphocytes: comparison of down-regulation in vivo and in vitro.

beta-Adrenergic receptors on isolated human lymphocytes were enumerated using 125I-cyanopindolol (125I-CYP), after a 90-min exposure to 50 mumols/l l-isoproterenol in vitro. No change in receptor density could be shown in assays performed at 37 degrees C, although a 40% reduction was apparent in binding studies carried out at 4 degrees C. In contrast, beta-adrenergic receptors on lymphocytes from mild asthmatics after a 3-week course of oral terbutaline showed a 40% reduction in receptor density regardless of the assay temperature, in addition to a 2.5-fold reduction in the receptor affinity for isoproterenol. The data are consistent with reports that a fraction of receptors are sequestered during short-term exposure to agonists. Sequestered receptors may or may not be detected by radioligand binding assays depending on the ligand of choice, temperature of the binding assay and duration of prior exposure to the agonist. After extended exposure to an agonist in vivo, the number of surface receptors was reduced, and sequestered receptors were not present, presumably as a result of degradation.

Adrenergic beta-Antagonists↗
PubMed1989

Effects of protein kinase inhibitor, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine, on beta-2 adrenergic receptor activation and desensitization in intact human lymphocytes.

To investigate the role of protein kinases in agonist-mediated beta-2 adrenergic receptor regulation, the effects of the protein kinase A and C inhibitor, H-7 [1-(5-isoquinolinylsulfonyl)-2-methylpiperazine], on isoproterenol-induced beta adrenoceptor activation and desensitization have been studied in intact human lymphocytes. In the presence of the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, H-7 potentiated 10(-8) to 10(-4) M isoproterenol or prostaglandin E1-induced cyclic AMP (cAMP) accumulation in a dose-dependent manner. We failed to observe any effect of H-7 on forskolin-induced cAMP accumulation. These effects of H-7 are probably not due to its inhibition of phosphodiesterase. In addition, whereas up to 10(-3) M H-7 had no beta adrenergic receptor blocking effect, preincubation of intact cells with 10(-3.5) M H-7 partially prevented 50 nM isoproterenol-induced beta-2 adrenergic receptor desensitization in terms of decreases in beta adrenoceptor density (maximum binding), isoproterenol-mediated cAMP responsiveness and high affinity receptor binding for agonist. Interestingly, 10(-3.5) M H-7 alone treated cells also showed an up-regulation of cell surface beta receptor density (maximum binding) and increased cAMP responsiveness to isoproterenol stimulation. The mechanisms are unclear. If these effects occur as a result of inhibition by H-7 of protein kinase A and/or C, it may suggest an important role of protein kinase A and/or C in agonist-induced beta-2 adrenergic receptor regulation.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1989

Effects of calcium channel blockers and ketotifen on beta 2 adrenergic receptor regulation in intact human lymphocytes.

Effects of three calcium channel blockers (nifedipine, NIF; verapamil, VER and diltiazem, DIL) and one antiallergic drug, ketotifen (KET) on isoproterenol (ISO)-induced beta 2 adrenergic receptor desensitization and resensitization have been studied with intact human lymphocytes in vitro. While incubation of lymphocytes with 1.0 microM NIF, VER, or DIL alone neither changed [3H]-CGP-12177 binding (Bmax) nor increased cAMP responsiveness to ISO, they all partially prevented 50 nM ISO-induced beta 2 adrenoceptor-adenylate cyclase uncoupling. VER and DIL also partially prevented beta 2 adrenoceptor down-regulation, but NIF did not. In contrast, 10 microM KET not only diminished ISO-induced desensitization but also accelerated subsequent resensitization. KET alone also induced an up-regulation of cell surface beta adrenergic receptors. The effects of these compounds on beta 2 adrenoceptor regulation may partially explain their potentiation of ISO-induced cAMP accumulation in lymphocytes.

Adrenergic beta-Antagonists↗
PubMed1988

The effects of calcium channel blockers on isoproterenol induced cyclic adenosine 3',5'-monophosphate generation in intact human lymphocytes.

We have investigated the effects of clinically available calcium channel blockers (nifedipine, verapamil and diltiazem) on isoproterenol stimulated cyclic adenosine 3',5'-monophosphate (cyclic AMP) generation in intact human lymphocytes. After preincubation of various calcium antagonists with intact lymphocytes at 37 degrees C for 15 minutes, 10 microM nifedipine or verapamil partially inhibited isoproterenol induced cyclic AMP generation in the presence of cyclic AMP phosphodiesterase inhibitor (3-isobutyl-1-methylxanthine) while they alone had no effect on cyclic AMP level at a concentration of up to 100 microM. In contrast, 10 nM-1.0 microM nifedipine, verapamil or diltiazem potentiated cyclic AMP generation induced by isoproterenol in a dose dependent manner. Similar results were observed in the time course studies of cyclic AMP generation. These effects are somewhat similar to the effect of phenothiazine, a calmodulin inhibitor, which, at 10 microM (close to IC50), also potentiated the effects of isoproterenol. In contrast, lanthanum chloride (LaCl3), an extracellular inorganic calcium antagonist, at 1.0 mM, inhibited isoproterenol induced cyclic AMP generation. The biochemical mechanisms underlying these potentiating effects are unknown. It may be partly related to the effect of calcium channel blockers (at least for nifedipine) on preventing beta 2 adrenergic receptor desensitization. This may provide a potential mechanism for the synergistic effect between calcium channel blockers and beta 2 adrenoceptor agonists on bronchial dilatation.

1-Methyl-3-isobutylxanthine↗
PubMed1988

Forskolin potentiates isoproterenol induced beta adrenoceptor desensitization in intact human lymphocytes.

The effects of forskolin on L-isoproterenol induced beta adrenoceptor desensitization in intact human lymphocytes from healthy subjects were studied. Exposure of intact lymphocytes to 50 microM L-isoproterenol for 150 minutes at 37 degrees C induced a 18% loss in beta adrenergic receptor density (Bmax) as characterized by using [3H]-DHA at 25 degrees C (23% loss, at 4 degrees C) as well as a significant loss in cyclic AMP responsiveness of the cell to isoproterenol restimulation. The addition of 10 microM forskolin to 50 microM isoproterenol potentiated isoproterenol induced beta 2 adrenoceptor desensitization as shown by further reduction in [3H]-DHA binding sites (decreased by 40% at 25 degrees C, 45% at 4 degrees C) and corresponding decrease in cyclic AMP responsiveness. These suggest that isoproterenol and forskolin act in a cooperative manner not only in the activation of adenylate cyclase and cyclic AMP generation but also in the regulation of hormone receptor and adenylate cyclase coupling.

Colforsin↗
PubMed1987

Ketotifen increases cyclic adenosine 3',5'-monophosphate in intact human lymphocyte and potentiates other adenylate cyclase activating agents.

We have investigated the effects of ketotifen on the cyclic adenosine 3',5'-monophosphate (cyclic AMP) response of intact human lymphocyte and its interaction with adenylate cyclase activating agents. In the presence of cyclic AMP phosphodiesterase inhibitor (3-isobutyl-1-methyl-xanthine), ketotifen (10(-8)-10(-4) M) caused an 80% increase in cyclic AMP content of human lymphocyte, a magnitude similar to that observed with hydrocortisone. The cyclic AMP level peaked at about 15 minutes and remained elevated for at least 45 minutes. In addition, ketotifen (10(-6)-10(-4) M) markedly potentiated the effect of several adenylate cyclase stimulating agents, including L-isoproterenol, prostaglandin E1 and forskolin. The biochemical mechanisms underlying these effects are unknown. It may be at least partly related to the ability of ketotifen to reverse and prevent beta 2 adrenoceptor desensitization and to promote the formation of hormone - nucleotide - high affinity receptor complex. These effects may contribute to its prophylactic effect in the treatment of bronchial asthma.

Adenylyl Cyclases↗
PubMed1987

The effects of tetramethylpyrazine on the human platelet alpha 2 adrenergic receptor adenylate cyclase system.

The binding properties of tetramethylpyrazine (TMPZ), a commonly used cardiovascular drug in China, to alpha 2 adrenergic receptors in human platelets were investigated. Increasing concentrations of TMPZ inhibited [3H]-yohimbine binding in intact platelets. The displacement curve was parallel to those of clonidine and yohimbine, with a Ki of 7.7 X 10(-5) M and an IC50 of 1.2 X 10(-4) M. In platelet membranes, increasing concentrations of TMPZ shifted the saturation binding curves of [3H]-yohimbine to the right and caused the dissociation constant (KD) to increase gradually. Higher concentrations of [3H]-yohimbine overcame the inhibition of TMPZ. Furthermore, in platelet cyclic AMP generation experiments, higher concentrations of TMPZ (10(-4)M-10(-6)M) inhibited the cyclic AMP increases induced by 10(-5) M PGE1. However, in the presence of an alpha 2 adrenergic receptor agonist (L-epinephrine), TMPZ blocked the inhibitory effect of L-epinephrine on cyclic AMP increases induced by PGE1. These properties suggested that TMPZ is an alpha 2 adrenergic receptor partial agonist. These effects may provide potential mechanisms for the cardiovascular actions of TMPZ.

Adenylyl Cyclase Inhibitors↗
PubMed1986

Invasive verrucous carcinoma of urinary bladder treated by irradiation.

A case of inoperable, invasive verrucous carcinoma of the urinary bladder treated by irradiation is presented. The incidence of anaplastic transformation of verrucous carcinoma after irradiation is lower and the coincidence of verrucous carcinoma and well-differentiated squamous carcinoma higher than is generally recognized. Radiation should be considered in inoperable cases. The pertinent literature is reviewed.

Aged↗
PubMed1986

Salivary duct adenocarcinoma: a high grade malignancy.

Salivary duct carcinomas of the major salivary glands have two major distinguishing features. They closely resemble ductal carcinomas of the breast and they are high-grade malignancies. In general, but particularly for carcinomas measuring three or more centimeters in size, the clinical course is one characterized by a resistance to local control, metastases to regional lymph nodes and distant sites, and death within a few years after primary surgical treatment.

Adenocarcinoma↗
PubMed1986

Bronchodilator effects of caffeine in coffee. A dose-response study of asthmatic subjects.

Although caffeine is a universal drug and has multiple pharmacologic and physiologic actions in man, there are surprisingly few objective data about its effect on pulmonary function. We conducted a short-term, double-blind, randomized crossover study in nine asthmatic adults who ingested decaffeinated coffee containing varying amounts of added caffeine (mean of 0.2,2.5,5.6, and 7.2 mg/kg of body weight) on different days. The subjects also ingested decaffeinated coffee and aminophylline (200 mg) on a separate day of study. Baseline and post-drug determinations of serum levels of caffeine and theophylline, forced expired volume and flow, specific airway conductance (Gaw/VL), vital signs, and reported symptoms were obtained. Peak increases in serum caffeine concentrations (mean, 12.4 micrograms/ml +/- 1.5 micrograms/ml) occurred 45 minutes following the highest dose of caffeine (7.2 mg/kg), whereas the peak theophylline level (mean 3.8 micrograms/ml +/- 0.4 micrograms/ml) occurred 90 minutes following oral administration of aminophylline (mean theophylline, 2.6 mg/kg). Comparable peak increases in the forced expiratory volume in one second (FEV1), the forced expiratory flow during the middle half of the forced vital capacity (FEF25-75%), and Gaw/VL occurred at 120 minutes following aminophylline and the highest dose of caffeine, indicating that caffeine is an effective bronchodilator but is only 40 percent as active as an equivalent molar dose of theophylline. Regression analysis revealed statistically significant dose-response relationships between peak increases in serum caffeine concentrations and increases in FEV1, FEF25-75%, and Gaw/VL from baseline values. These findings have diagnostic and therapeutic implications regarding the use of caffeine prior to tests of pulmonary function and as a dietary agent, alone or in combination with theophylline.

Administration, Oral↗
PubMed1985

Experience with outlet strut fracture of the Björk-Shiley convexoconcave mitral valve prosthesis.

Within a period of 15 months, we encountered five patients with outlet strut fracture of the Björk-Shiley convexoconcave mitral valve prosthesis. All of the patients had acute failure of the left side of the heart and pulmonary edema. The diagnosis was made by review of the chest roentgenogram which showed features of pulmonary edema; both the outlet strut and the tilting disc were missing from the mitral prosthesis. The "missing" components might be found in the left side of the heart or in the course of the thoracic aorta. Emergency reoperation was carried out on three patients, and there were two survivors. It is essential to recognize this potentially fatal complication and undertake immediate surgical intervention. We performed the original valvular replacement operations in four of the five patients. The probability of outlet strut fracture occurring in our series of 237 patients with a Björk-Shiley convexoconcave mitral valve prosthesis is 1.69%, or 0.076 per 100 patient months.

Adolescent↗
PubMed1985

Rebound hyperresponsiveness to muscarinic stimulation after chronic therapy with an inhaled muscarinic antagonist.

In 9 young subjects with mild asthma, we investigated the possibility that chronic daily administration of an inhaled muscarinic antagonist (ipratropium bromide) might increase the response of muscarinic receptors in airway smooth muscle to agonist stimulation caused by receptor upregulation. Subjects inhaled 60 micrograms of ipratropium 4 times daily for 3 wk. Methacholine bronchoprovocation (with or without acute pretreatment with ipratropium) was performed before (control period) and during 3 wk of daily ipratropium therapy (medication period). At the end of the medication period, subjects returned at 12, 24, 48, and 72 h after the last dose of ipratropium (withdrawal period) to determine the provocative concentration of methacholine producing a 20% decrease in FEV1 (PC20). During the medication period, there was no significant diminution of the acute bronchodilator response to ipratropium or of the protective effect of ipratropium against methacholine-induced bronchospasm when compared with the control period. During the withdrawal period, mean in PC20 was significantly less (increased airway responsiveness) at 24 h than during the control period (p less than 0.01) and returned to the control period value within 48 to 72 h. We conclude that daily administration of ipratropium to mildly asthmatic subjects for 3 wk does not produce tolerance to either the bronchodilator effect of ipratropium or to its inhibition of methacholine-induced bronchospasm but does induce transient supersensitivity of airway cholinergic receptors to muscarinic stimulation.

Adult↗
PubMed1985

The effects of some beta lactam antibiotics on (3H)-methyl-yohimbine binding to intact human platelets.

Several antibiotics have been reported to cause a bleeding diathesis in man, characterized by reduced platelet aggregation. We investigated the effects of several of the penicillins and of moxalactam on the binding of (3H)-methyl-yohimbine to intact human platelets. The (3H)-methyl-yohimbine binding met the criteria for interaction at an alpha2 adrenergic binding site and showed low interindividual variability. Penicillin G, ticarcillin, carbenicillin, piperacillin and moxalactam all inhibited (3H)-methyl-yohimbine binding, but at concentrations far in excess of clinically achievable plasma levels. We conclude that these compounds exert their antiplatelet effects by a mechanism other than competitive inhibition of catecholamine binding.

Adrenergic alpha-Antagonists↗
PubMed1982

Selective subsensitization of beta-adrenergic receptors in central airways of asthmatics and normal subjects during long-term therapy with inhaled salbutamol.

In five subjects with mild asthma and in five normal subjects, we determined the effect of a 4 wk course of inhaled salbutamol (albuterol), 200 micrograms q.i.d., on (1) acute bronchodilator responsiveness, (2) bronchial sensitivity to inhaled histamine, (3) beta-adrenergic protection against histamine-induced bronchospasm, and (4) beta-receptor density of peripheral blood lymphocytes. We observed a diminution in central airway bronchodilator responsiveness (as measured by airway conductance responses) to acutely inhaled salbutamol and to subcutaneous terbutaline in both groups of subjects, although only the response to subcutaneous terbutaline was statistically significant (p less than 0.02). On the other hand, no impairment of small airway bronchodilator responsiveness was noted in either group of subjects when responses were measured as partial expiratory flow rates at 60% below total lung capacity. These findings suggest the development of selective subsensitization of beta-receptors in the larger central airways, where a proportionately greater amount of the inhaled beta-agonist aerosol would necessarily be deposited. A greater loss of protection against histamine-induced bronchospasm was seen in asthmatics than in normals (approximately twofold), although the difference was not significant. A modest but not significant reduction in peripheral blood lymphocyte beta-receptor density was observed by the end of the 4 wk treatment period. The possibility that the observed changes in bronchodilator responsiveness might influence the morbidity and mortality associated with bronchial asthma is discussed.

Administration, Intranasal↗