Biomedical subjects

J Ng

Publications and source records attributed to J Ng.

At least 127 records · Page 7Linked to original sources

PubMed1990

A generalized chain binomial model with application to HIV infection.

The original Reed-Frost formulation of the chain binomial model is mathematically equivalent to a stochastic model allowing a Poisson number of effective contacts in a time interval. Their formulation cannot accommodate survey data that necessarily correspond to more complex distributions of partners or contacts, or to large populations where complete random mixing is unlikely. This paper generalizes the Reed-Frost model to accommodate these situations in both the one- and two-population settings. The extension to multiple populations is also outlined. Using the model to predict HIV incidence in San Francisco's homosexual population, we show that the total number of contacts over all partners is more important than the distribution of contacts among partners in determining the number of infected.

HIV Infections↗

PubMed1990

Use of molecular typing to study the epidemiology of Serratia marcescens.

Although Serratia marcescens is a well-known nosocomial pathogen, investigation of its hospital ecology has been limited by the lack of available typing techniques. During an investigation of the occurrence of this organism in a neonatal intensive care unit, we evaluated a number of such techniques. Using a selective medium, we conducted prospective surveillance of neonatal rectal colonization and environmental contamination with S. marcescens. In 8 months of surveillance, 5.1% (20 of 394) of the infants admitted to the unit became colonized. Most sink surfaces and drains were also culture positive. Differences between isolates could not be detected in biotypes from a commercial identification system (MicroScan) or by antibiograms, total protein fingerprints, or plasmid profiles. Serogrouping and genomic DNA restriction endonuclease analysis revealed the presence of six strains that colonized infants and a similar number of environmental strains. These two methods were concordant, with the exception that genomic DNA analysis demonstrated lack of relatedness between some strains within the same serogroup. DNA restriction endonuclease analysis was practical and reliable. The differences this method detected between environmental and neonatal strains provided strong evidence that the environment was not an important reservoir for S. marcescens in our neonatal intensive care unit.

Cross Infection↗

PubMed1990

MR imaging of the knee: pseudotear of the lateral meniscus caused by the meniscofemoral ligament.

Sagittal MR images of the knee often show a linear band of increased signal in the medial aspect of the posterior horn of the lateral meniscus that can be confused with a meniscal tear. This pseudotear is due to the meniscal insertion of the meniscofemoral ligament. To study the normal appearance of the medial aspect of the posterior horn of the lateral meniscus, we analyzed 109 MR examinations and correlated the findings with the results of arthroscopy. The meniscofemoral ligament was visualized in 54 cases (50%), and in 42 cases (39%) it caused the appearance of a pseudotear on sagittal images. The pseudotear had one of two orientations. The most common (35/42) was an oblique orientation coursing from the superior surface posteriorly and inferiorly. The other (7/42) was a more vertical orientation parallel to the base of the meniscus. Knowledge of the characteristic location and orientation of the meniscofemoral ligament should help to distinguish it from a true meniscal tear on MR images.

Adolescent↗

PubMed1989

Prognostic factors and progress for ambulation in elderly patients after hip fracture.

A longitudinal study of the ambulation progress was done on 102 patients in the first 9 wk after an operation for repair of hip fractures. The time taken to achieve a stable walking pattern from frame to a cane was recorded for every patient. Results showed that 82.2% of the patients were able to walk with a cane at 4 wk postoperatively. Of the remaining 17.8% of the patients, 7.7% were able to walk with a cane at 6 wk whereas 10.1% were not able to walk with a cane at 6 wk. Several factors including the age, sex, mental state, the type of operation and the preoperative ambulation level of the patients were studied to predict the ambulation progress of the patients. The most important factors affecting the ambulation progress were the age and the preoperative ambulation level of the patient. Because of the general trend in the aging of the population, an increase in the number of hip fractures is expected. The result of this study may help in predicting the prognosis and provide guidance for restoring the function of the patients.

Aged↗

PubMed1989

Traumatic knee injuries: the accuracy of MRI compared with arthroscopy.

Forty-three knees in 43 patients were evaluated preoperatively with magnetic resonance imaging (MRI). Both menisci and cruciate ligaments subsequently were examined directly with arthroscopy. A grading scale was used to evaluate intrameniscal signal intensity and to predict the presence of meniscal tear using MR. Compared with arthroscopy, the sensitivity, specificity and accuracy of MRI were, respectively, 100%, 88% and 93% for tears of the medial meniscus; 72.7%, 93.7% and 88.4% for tears of the lateral meniscus; 100%, 96.7% and 97.7% for tears of the anterior cruciate ligament. There were no posterior cruciate ligament tears, and none were suggested from the images. Our results show that MRI is a valuable diagnostic aid in the management of traumatic knee injury.

Adolescent↗

PubMed1989

Ultrasound guided drainage of pleural fluid.

Ultrasound guided drainage has been reported as a highly successful drainage procedure. Computed tomography (CT) and fluoroscopy also have been cited as favorable imaging modalities for the treatment of pleural effusion. With its extreme sensitivity to fluid collections and rapid and accurate localization of fluid, real-time ultrasound has become the primary imaging modality for the interventional drainage of pleural fluid. This is a retrospective study of patients with radiographically suspected pleural effusion, using ultrasonic scanning for possible drainage. A special bedside drainage technique in critically ill patients also is described.

Drainage↗

PubMed1988

Regulation of receptor-mediated calcium influx across the plasma membrane in a human leukemic T-cell line: evidence of its dependence on an initial calcium mobilization from intracellular stores.

It has been repeatedly shown that stimulation of a human leukemic T-cell line, JURKAT, by lectins such as phytohaemagglutinin and anti-T3 antibody (OKT3) leads to an elevation in the concentration of cytosolic free Ca2. This Ca2+ transient results from both an intracellular mobilization and an influx of Ca2+ through specific membrane channels. The objective of this study was to investigate the mechanism by which receptor-mediated influx of Ca2+ is regulated in JURKAT cells, which demonstrably lack 'voltage-dependent calcium channels'. It was found that upon increased loading with quin2 or 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetate (BAPTA) there was a pronounced decline of both phytohaemagglutinin-stimulated and OKT3-stimulated influx of 45Ca2+. Using 15 microM quin2/AM or 30 microM BAPTA/AM, agonist-stimulated 45Ca2+ influx was almost totally abolished. At these concentrations of both quin2/AM or BAPTA/AM, phytohaemagglutinin and OKT3 could still induce a rise of cytosolic free Ca2+ above 200 nM. In the presence of La3+ (200 microM), which completely inhibited the agonist-induced 45Ca2+ influx, both phytohaemagglutinin and OKT3 were able to raise the concentrations of cytosolic free Ca2+ to well above 200 nM by merely mobilizing Ca2+ from intracellular stores alone. The data suggest that an agonist-induced increase in the concentration of cytosolic free Ca2+, due to mobilization from intracellular stores, could either directly or indirectly, initiate receptor-mediated Ca2+ influx across the plasma membrane in JURKAT cells.

Aminoquinolines↗

PubMed1988

IFN-gamma treatment of K562 cells inhibits natural killer cell triggering and decreases the susceptibility to lysis by cytoplasmic granules from large granular lymphocytes.

Pretreatment of human K562 leukemia cells with rIFN-alpha and rIFN-gamma resulted in decreased susceptibility to lysis by human peripheral blood NK cells. The reduction of NK-susceptibility after IFN treatment was not due to a general effect of IFN on the stability of the cell membrane because the susceptibility of K562 cells to lysis by antibodies plus C, distilled water, or lysolecithin was unaffected. Binding studies with effector cell preparations enriched for NK cells with large granular lymphocyte morphology revealed no difference in binding to control and IFN-gamma-treated target cells. The sensitivity to soluble NK cytotoxic factors was not affected significantly by the IFN treatment. In contrast, the susceptibility of IFN-treated target cells to the cytotoxic activity of purified cytoplasmic granules from a rat large granular lymphocyte tumor was significantly reduced, indicating that the IFN-induced resistance acted at the level of susceptibility to the lytic mechanism of NK cells. However, IFN-alpha was more effective than IFN-gamma in inducing resistance to the cytoplasmic granules although resulting in only a weak resistance in the cell-mediated cytotoxic assay. IFN-gamma but not IFN-alpha caused a reduction in the frequency of effector cells that had reoriented their Golgi apparatus toward their bound target cell. In addition, IFN-gamma treated K562 cells failed to elicit an influx of Ca2+ into effector cells. Taken together, the results suggest that IFN-gamma in addition to an increased resistance to the lytic molecules released by NK cells can also induce changes in the target cells which prevent the triggering and activation of the effector cell.

Animals↗

PubMed1987

Studies on the calcium dependence of human NK cell killing.

T lymphocytes and NK cells depend on extracellular Ca2+ to mediate cellular cytotoxicity. In the present work, we have used pharmacological tools to analyze the nature of this calcium dependence. Ca2+ channel blockers like nifedipine greater than or equal to diltiazem greater than verapamil greater than cobalt chloride inhibited NK killing but at concentrations higher than those sufficient to block voltage-operated Ca2+ channels. Quercetin and TMB-8 also suppressed killing. Depolarization or NK cells with high K+ concentration resulted in partial inhibition of lysis in contrast to hyperpolarization with K+ ionophore valinomycin which had no effect. Depolarization of hyperpolarization in the presence of a protein kinase C activator (phorbol ester, TPA) did not initiate killing of NK resistant target cells. Of the two K+ channel inhibitors tested, 4-AP and TEA, only 4-AP was inhibitory for NK killing. No release of membrane-bound Ca2+ as judged by chlorotetracycline fluorescence could be detected in the NK cell population during binding to target cells although an influx of 45Ca2+ into the NK cell population was found. Treatment of NK cells with calcium ionophore A23187 did not trigger killing, but lysis could be induced by simultaneous stimulation with A23187 and TPA. The results indicate that NK killing depends on Ca2+ channels that are different from voltage operated channels and that intracellular Ca2+ may act in concert with protein kinase C activation.

Calcimycin↗

PubMed1987

Studies of gene transfer and reversion to mitomycin C resistance in Fanconi anemia cells.

As a first step to the cloning of the Fanconi anemia (FA) gene, we have attempted to correct the sensitivity of FA cells to DNA crosslinking agents by the introduction of wild-type DNA. The protocol involved the introduction of both genomic and pRSVneo DNA, selection for G418-resistant colonies and the subsequent selection of mitomycin C-resistant cells from the latter. Preliminary experiments indicated that untransformed FA cells were not suitable recipients for the introduction of foreign DNA, so all experiments were performed with an SV40-transformed FA cell line. Approximately 40,000 G418-resistant colonies were obtained in 5 separate experiments at an overall frequency of about 5 X 10(-4). These were then selected in mitomycin C and 15 colonies were recovered. Colonies were obtained with wild-type DNA (both human and rodent) and with FA DNA at about the same frequency of 2 X 10(-7). Colonies were isolated and shown to have a stable, partial (from 25 to 90% of wild-type) resistance to mitomycin C. One colony was also shown to be partially resistant to two other DNA crosslinking agents, diepoxybutane and nitrogen mustard. This clone also had an intermediate level of spontaneous and MMC-induced chromosome aberrations. pRSVneo, but not rodent, DNA could be demonstrated in the high molecular weight fraction of several colonies. Thus, it is likely that these colonies represent partial revertants rather than transfectants. These mitomycin C-resistant FA cells should be useful for the biochemical analysis of the FA mutation.

Anemia, Aplastic↗

PubMed1987

Characterization of PHA and anti-T3 induced transduction mechanisms in a human T-cell leukaemia line.

Stimulation of the T-cell line JURKAT with PHA or anti-T3 antibody leads to a rapid and sustained rise of cytosolic free Ca2+, as determined by quin2 fluorescence measurements. Pertussis toxin and N-ethylmaleimide, substances known to inactivate a regulatory N-protein, caused partial to complete inhibition of the cytosolic free Ca2+ response induced both by anti-T3 or PHA. The high cytosolic free Ca2+ level induced by anti-T3 or PHA declined more rapidly after addition of phorbol ester, phorbol myristate acetate (PMA). PMA did not affect cytosolic free Ca2+ changes induced by ionomycin indicating that the effect of PMA is due to a direct inhibitory effect on a transduction mechanism and not to activation of Ca2+ extrusion. Our data suggest that a regulatory N-protein is involved in the transduction of the PHA and anti-T3 response into a rapid and sustained elevation of cytosolic free Ca2+. Activation of protein kinase C by PMA modulates the calcium response in JURKAT cells, suggesting that protein kinase C may be involved in feedback regulation of the transduction mechanism.

Calcium↗

PubMed1987

The effects of high Na and Cl concentrations on rat proximal volume and Na fluxes at zero tubular flow.

1. In vivo micropuncture techniques, with and without peritubular capillary perfusion, were used to study the effects of high extracellular Na and Cl concentrations on transepithelial volume (Jv) and sodium (JNa) fluxes in rat proximal tubules. 2. In a double blind manner, the shrinking drop technique of Gertz was used to measure Jv; JNa was calculated from this and the tubular fluid Na concentration. 3. At both 184 and 279 mmol/l pericellular Na concentrations (both inside and outside the tubular epithelium), net Jv decreased significantly by 15 and 64%, respectively. Net JNa remained constant at 184 but decreased by 29% at 279 mmol/l Na concentration. 4. Thus, at both Na concentrations, when translated to free flow conditions, fractional Na reabsorption must have decreased. These findings, also supported by previous results at these Na concentrations, indicate that active Na transport was inhibited by high pericellular Na concentrations. 5. When intratubular Cl concentration was varied between 108 and 138 mmol/l while peritubular Cl was maintained constant (blood perfusing the capillaries), neither Jv nor JNa changed. Thus, at zero tubular flow, differential Cl/HCO3 concentrations do not provide significant driving forces for net Jv or JNa. 6. When only intratubular but not peritubular Na was elevated to 279 mmol/l, Jv and JNa increased markedly by 50 and 187%, providing evidence that a true solvent drag (solute drag) effect does exist in rat proximal tubules. 7. These findings offer a mechanism to explain why Na reabsorption is not increased when the filtered load of Na is increased with an elevation of plasma Na.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

Characterization of a simian virus 40-transformed Fanconi anemia fibroblast cell line.

We have characterized a SV40-transformed human fibroblast cell line (GM6914) derived from a patient with Fanconi anemia (FA) in order to establish its usefulness for biochemical and genetic experiments, including DNA-mediated gene transfer. GM6914 cells have a growth rate similar to that of SV40-transformed normal human fibroblasts and an indefinite lifespan in culture. As has been established for other FA cell types, GM6914 cells have an increased sensitivity to DNA-crosslinking agents such as mitomycin C (MMC). The D10 for GM6914 cells is 8 times lower than for equivalent controls. GM6914 cells also have an elevated frequency of spontaneous chromosome aberrations and this frequency can be increased by MMC concentrations which show no effect on control cells. Genetic complementation studies with lymphoblasts derived from two affected sibs of the donor of GM6914 cells show that GM6914 belongs to FA complementation group A. In DNA-transfection studies using plasmid pRSVneo, colonies of GM6914 cells resistant to the drug G-418 were observed at frequencies ranging from 1.7 to 16 X 10(-4), values similar to those observed with several other SV40-transformed human cell lines. GM6914 should be a useful recipient cell line in experiments using DNA-mediated gene transfer to clone the normal allele of the gene which is defective in FA complementation group A. GM6914 would also be an excellent cell line for studies on mutagenesis, recombination and repair using plasmid vectors.

Anemia, Aplastic↗

PubMed1986

Phorbol ester regulation of Ca2+ flux during natural, lectin and antibody-dependent killing.

Phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), an activator of protein kinase C, suppresses natural, lectin and antibody-dependent killing by normal human lymphocytes in short-term radioisotope release assays. Fifty percent inhibition of killing of lymphoid target cells was seen at approximately 5 ng/ml TPA and inhibition was further potentiated by the presence of monocytic cells. In contrast, TPA increased killing of K-562 erythroleukaemic cells by non-adherent NK cells with optimal activity around 1 ng/ml. Two anti-estrogenic drugs, tamoxifen and clomiphene, known to inhibit protein kinase C, gave near to complete inhibition of NK killing at concentrations 12 microM and 30 microM, respectively. Retinal, another protein kinase C inhibitor, inhibited both antibody-dependent killing and lectin-dependent killing. An influx of 45Ca2+ into the effector population was found during effector-target cell conjugation and this flux was suppressed at TPA concentrations similar to those that suppressed killing. The results suggest that killing depends on a co-ordinated activation of protein kinase C together with a channel-dependent calcium influx. TPA may suppress killing by a negative feedback effect of protein kinase C on the hydrolysis of inositol phospholipids, as demonstrated in many other systems, or through the down-regulation of cell surface receptors required for triggering of lysis.

Antibody-Dependent Cell Cytotoxicity↗

PubMed1985

Action of novel eicosanoids lipoxin A and B on human natural killer cell cytotoxicity: effects on intracellular cAMP and target cell binding.

Lipoxin A (5,6,15L-trihydroxy-7,9,11,13-eicosatetraenoic acid) and lipoxin B (5D,14,15-trihydroxy-6,8,10,12-eicosatetraenoic acid), two newly isolated compounds derived from the oxygenation of arachidonic acid in human leukocytes, inhibit the cytotoxic activity of human natural killer (NK) cells. Dose-response studies showed that both lipoxin A and lipoxin B inhibit, at submicromolar concentrations (ID50 10(-7) M), NK cell activity assayed against K562 target cells. Prostaglandin E2 (PGE2) also inhibited cytotoxicity, whereas both 15-HETE (5(S)-hydroxy-5,8,11,13-eicosatetraenoic acid) and leukotriene B4 (synthetic and biologically derived) were ineffective. PGE2 stimulated a time- and dose-dependent increase in intracellular cAMP, which was accompanied by a decrease in NK target cell binding. Lipoxin A and lipoxin B did not elevate intracellular cAMP, nor did they inhibit target cell binding. Together these findings suggest that lipoxin A and lipoxin B abrogate NK cell cytotoxicity at a step distal to target effector cell recognition. In contrast, PGE2 appears to exert its effect, at least in part, on cytotoxicity indirectly by decreasing the binding between target and effector cells (in vitro). Moreover, they suggest that novel oxygenated derivatives of arachidonic acid (i.e., lipoxin A, lipoxin B) may regulate the activities of NK cells.

Binding Sites↗

PubMed1985

Biologic activities of recombinant human interleukin 2 on murine lymphocytes.

Recombinant human IL-2, produced by yeast cells, was tested in a number of in vitro responses with murine lymphocytes. The responses studied included proliferation of a cloned murine T lymphocyte line, generation of cytotoxic responses, recall of cytotoxic memory, and restoration of responses in spleen cells taken from cyclophosphamide-treated mice. In all cases, the recombinant human IL-2 had the same activity as purified murine IL-2. The recombinant material represents a source of IL-2 free of other lymphokines. The responses described in this work can therefore be ascribed to the direct effects of human IL-2, of known sequence, on the cells of interest.

Animals↗

PubMed1985

Left ventricular function in uremia: echocardiographic and radionuclide assessment in patients on maintenance hemodialysis.

Echocardiography and radionuclide ventriculography were performed in 37 uremic patients on maintenance hemodialysis with no apparent coronary artery disease, pericardial effusion, valvular heart disease or heart failure. These non-invasive studies were performed during the interdialytic period (about 18 hours after a dialysis). Sixty-two percent of our patients had abnormal left ventricular function with one or more abnormal echocardiographic parameters. The significant abnormalities were enlargement of the left ventricular cavity, a reduction of myocardial contractility, and thickening of the left ventricular posterior wall. Similar findings were found in 10 undialyzed uremic patients. Measurement of cardiac index and ejection fraction were found to be inadequate for a full assessment of left ventricular function and other parameters such as the mean velocity of circumferential fiber shortening and mean normalized posterior wall velocity should be included. There is a significant number of hemodialysis patients (7/37) with congestive cardiomyopathic features on the echocardiogram. Their clinical features are no different from the other patients in this study, except they have a significantly higher prevalence of uremic hyperparathyroidism. Our findings support that the existence of a specific uremic cardiomyopathy and uremic hyperparathyroidism may play an important role in the pathogenesis.

Adult↗

PubMed1984

A prospective randomized trial of low-dose versus high-dose steroids in cadaveric renal transplantation.

Low-dose steroid regimens, in combination with azathioprine, have become increasingly common for immunosuppression of renal transplant recipients. The change from conventional high-dose steroid regimens was prompted by the results of several prospective trials that showed similar graft survivals with high-dose and low-dose steroids, but a lower incidence of steroid-induced complications in low-dose-steroid--treated patients. However, the number of patients entered into the trials was small, and consequently there remained a possibility that a clinically relevant difference in graft survival could have remained undetected. A multi-center prospective trial was performed to compare graft survival with high-dose (91 patients) and low-dose (98 patients) oral steroids in combination with azathioprine. There was significantly worse graft survival in the low-dose group. The difference was largely due to a poor graft survival in patients receiving low-dose steroids and azathioprine less than 1.75 mg/kg/day. Graft survivals were similar in the high-dose and low-dose steroid patients who received azathioprine doses of greater than 1.75 mg/kg/day. The results indicate that the combination of low doses of both steroids and azathioprine provides inadequate immunosuppression in renal transplantation, although higher doses of azathioprine allow the use of low-dose steroids without significantly more graft losses than with high-dose steroids.

Adult↗