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Biomedical subjects

C Chan

Publications and source records attributed to C Chan.

At least 235 records · Page 13Linked to original sources

Role of Ly-6 in lymphocyte activation. II. Induction of T cell activation by monoclonal anti-Ly-6 antibodies.

The Ly-6 locus controls the expression and/or encodes for alloantigenic specificities found primarily on subpopulations of murine T and B lymphocytes. We have recently identified and characterized a new rat mAb, D7, that recognizes a nonpolymorphic Ly-6 specificity. After crosslinking by anti-Ig reagents or by Fc receptor-bearing accessory cells, mAb D7 could induce IL-2 production from T cell hybridomas, and in the presence of PMA could trigger a vigorous proliferative response in resting peripheral T cells. The addition of mAb D7 to cultures of antigen- and alloantigen-, but not mitogen-stimulated T cells resulted in a marked augmentation of the proliferative response. A number of other well-characterized mAbs to Ly-6 locus products could also stimulate a T cell proliferative response after crosslinking by anti-Ig and in the presence of PMA. These results strongly suggest that Ly-6 molecules may play a critical role in the T cell activation cascade, either as receptors for an unidentified soluble or cell-associated ligand or as transducing molecules that modulate signals initiated by antigen stimulation of the T3-Ti complex.

Animals↗

Nutritional practices and outcome of extremely premature infants.

We analyzed the records of 182 newborns with birth weights under 1000 g, who survived longer than seven days, to determine risk factors for subacute mortality and morbidity. Statistical analysis using logarithm-linear modeling was used to identify complex interactions and to minimize confounding. Nosocomial infection, necrotizing enterocolitis, male gender, and chronic lung disease (CLD) were identified as independent risk factors for subacute mortality. Male gender and CLD were associated with increased mortality only among patients who received parenteral nutrition (PN). Moreover, PN, rather than enteral nutrition (EN), was a risk factor for delayed growth, nosocomial infection, and CLD. Delayed initiation of EN was associated with decreased necrotizing enterocolitis risk only among male infants with birth weights under 775 g. Our results do not support elective withholding of EN in other groups of extremely low-birth-weight infants. We conclude that indications for PN and for withholding initiation of EN in very-very-low-birth-weight infants need to be established by prospective studies.

Body Weight↗

Plaque retention on teeth restored with full-ceramic crowns: a comparative study.

Plaque accumulation was determined by using the plaque index of Silness and Löe on 150 crowns in 19 patients. The plaque indices for individual crowns in a quadrant were compared to the average plaque index of the quadrant in which the crowns were inserted (quadrant plaque index = 100%). This comparative study showed that Cerestore full-ceramic crowns have little soft debris retention (32%). Ceramometal crowns (90%), natural teeth (110%), cast gold restorations (148%), and acrylic resin veneer crowns (152%) have increasing plaque retention. The results indicate that ceramics are easily cleaned and exhibit low plaque retention. Increasing the area of ceramic surfaces on restorations decreases plaque retention.

Acrylic Resins↗

The question of ocular tolerance to intravitreal liquid silicone. A long-term analysis.

The authors report a retrospective review of 407 eyes that received intravitreal liquid silicone between 1961 and 1984. Initial anatomical success was noted in 270 eyes (66.3%), while initial functional success was achieved in 103 eyes (25.3%). Ten years postoperatively, approximately half of the eyes with initial functional success still had functional vision (49.2%). These eyes had less advanced proliferative vitreoretinopathy and fewer inferior breaks than others. Recurrent retinal detachment rather than late complications was the predominant cause of functional failure in those eyes losing functional vision in less than ten years postoperatively. Late complications were common and frequently required therapeutic intervention. Intravitreal liquid silicone was of great benefit to many monocular patients, but of little benefit to the binocular patients in our series.

Adolescent↗

Failure of urinary MHPG levels to predict treatment response in patients with unipolar depression.

The authors studied 64 depressed patients who were receiving a vanillylmandelic acid (VMA)-free diet and underwent a washout period (mean, 24 days) before treatment. During the washout period, a mean of 2.5 multiple 24-hour urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) samples per patient were collected. Thirty-four patients were then treated with a "noradrenergic" antidepressant only (e.g., imipramine), and seven were treated with a "serotonergic" antidepressant only (e.g., amitriptyline). Twelve patients received combined drug treatment and 11 others spontaneously remitted. Response to treatment was rated on a clinical global evaluation scale from 1 (little or no response) to 7 (maximum response). No relationship was found between response to treatment, type of treatment, and the average pretreatment 24-hour urinary MHPG level. The authors thus failed to confirm the hypothesis that a low MHPG level predicts response to antidepressant treatment.

Adult↗

[Pharmacokinetic and clinical studies of cefotiam in the perinatal period].

Patients, who had undergone cesarean sections, and those who had experienced premature rupture of membranes, received cefotiam (CTM) and the clinical efficacy and the safety for mothers and fetuses were investigated. At the same time, pharmacokinetic analysis was done to study the maternal fetal transfer. Following results were observed. In cases of premature rupture of membranes, the maternal-fetal transfer ratio after intravenous administrations of CTM was 50.3% at a dosage of 1 g. Maternal and fetal serum concentrations of CTM were maintained higher levels than the MIC80 (0.78 micrograms/ml) against major pathogens excluding anaerobic of gynecologic-obstetric infections and were maintained up to 5.87 hours and 6.15 hours in mothers and fetuses, respectively. The CTM was administered once every 12 hours at a dosage of 1 g to 38 cases up to the 3rd or 4th day of puerperium after the rupture of membranes. Also, the CTM was administered up to times of delivery to another 20 cases, in one of which the fetus developed pneumonia. The maternal-fetal prophylactic effect was recognized in 98.3% (57/58) of cases. Forty-three cesarean section cases received CTM at a dosage level of 1 g by one-hour intravenous drip infusion in the following manner: after surgery to the 4th day, twice a day; from the 5th to the 7th day, once a day. Postoperative prophylactic effect against infection was achieved in all the cases. In 1 case, a slight transient elevation in the maternal GOT was observed. Neonatal jaundice with total bilirubin levels higher than 15.0 mg/dl was observed in 19 neonates (32.8%) in the group in which premature rupture of the membranes had occurred. However, the cause/effect relationship between CTM and the total bilirubin levels is unclear. The maternal-fetal transition of CTM was excellent, and the safety toward the fetus and neonate was high. When an antimicrobial activity and pharmacokinetics are considered, CTM will be a useful drug in the treatment of perinatal infections.

Amniotic Fluid↗

Nephrotic syndrome associated with a clonal T-cell leukemia of large granular lymphocytes with cytotoxic function.

A 51-year-old man presented with a T-cell leukemia of large granular lymphocytes and rapidly developed a nephrotic syndrome due to presumptive minimal-change glomerulopathy. The E-rosette+, Ia+ cells demonstrated cytotoxic activity similar to that of natural killer lymphocytes but lacked other T-subset markers, except that one third of them bore Fc(IgG) receptors. Cytogenetic analysis revealed loss of chromosome 10 and the translocation (1;10)(p11;q11) in all metaphases. Regression of the leukemia after chemotherapy was accompanied by a dramatic resolution of the nephrotic syndrome, suggesting that the activated granular lymphocytes induced the renal lesion. The close association of a clonal T-lymphoproliferative disorder with minimal-change nephrotic syndrome lends further support to current views implicating activated T cells or their products in the pathogenesis of this glomerulopathy.

Chromosomes, Human, 1-3↗

Effects of propranolol on atherogenesis in the cholesterol-fed rabbit.

These studies have examined the effects of dl-propranolol, d-propranolol, and metoprolol on aortic atherogenesis in the cholesterol-fed rabbit and have correlated the vascular effects of the drugs with their influence on blood pressure, plasma lipids and lipoproteins, arterial metabolism, and arterial permeability. dl-Propranolol, and, to a lesser extent, d-propranolol, used in clinically relevant doses of 5 mg/kg body weight per day, inhibited the development of aortic atherosclerosis in association with significant reductions in aortic free and esterified cholesterol content. No significant effects of the drugs on blood pressure or on the total amounts or types of circulating lipoproteins were apparent. Accumulation of cholesterol in the liver and adrenal gland was not influenced by propranolol. Aortic acyl CoA:cholesterol acyltransferase and lysosomal enzyme activities were reduced by propranolol administration, but the inhibition may have been secondary to the lesser degrees of atherosclerosis and cholesterol accumulation present. In vitro inhibition of acyl CoA:cholesterol acyltransferase activity by either dl- or d-propranolol was also observed, but occurred only at propranolol concentrations of 10(-3) M or greater. Treatment with dl-propranolol had no significant effect on the rate of transport of labeled albumin across the isolated carotid artery of cholesterol-fed rabbits. Metoprolol administration (6.25 mg/kg body weight per day) had no significant influence on atherogenesis or arterial metabolism in this model. The results suggest that propranolol inhibits in part the development of atherosclerosis in the cholesterol-fed rabbit, and that the effect may be related to a direct action on the arterial wall.

Animals↗

Role of the L3T4-antigen in T cell activation. II. Inhibition of T cell activation by monoclonal anti-L3T4 antibodies in the absence of accessory cells.

We have used two monoclonal antibodies (Mab) to the L3T4 antigen to reexplore the role of this molecule in the process of T cell activation. Both Mab (Gk1.5 and 2B6) were capable of inhibiting Con A-induced IL 2 production by a number of antigen-specific T cell hybridomas in an assay system that was free of major histocompatibility complex (MHC) class II antigen-bearing cells. The inhibition produced by the anti-L3T4 Mab was specific, because other Mab to cell surface antigens expressed on the hybridomas were without inhibitory effects. These studies rule out the possibility that the mechanism of inhibition by anti-L3T4 in this model is mediated by blocking interaction of L3T4 with MHC class II products. Taken together, these results and those of other groups of investigators, are most compatible with a dual function for L3T4 in T cell activation. L3T4 might first interact with MHC class II molecules or other molecules on target or accessory cells; L3T4 would subsequently transmit a signal that would regulate the activation process. Mab to L3T4 might exert inhibitory effects at one or both of these steps.

Animals↗

Influence of accessory cell and T cell surface antigens on mitogen-induced IL 2 receptor expression.

We have assessed the inhibitory effects of various monoclonal antibodies on the expression of the IL 2 receptor. Anti-LFA-1, but not anti-Ly-2, markedly inhibited the induction of the IL 2 receptor on the Ly-2+ subset. T-depleted spleen cells, L cells, and B lymphoma cells all functioned as potent accessory cells (AC) for the induction of the IL 2 receptor on L3T4+ T cells. Anti-LFA-1 inhibited the induction of the IL 2 receptor irrespective of the type of AC used. Anti-L3T4 only inhibited the induction of IL 2 receptor expression when L cells were the source of AC. The inhibitory capacity of anti-L3T4 was not related to the expression of Ia on the AC population, because the magnitude of inhibition was comparable in cultures containing either Ia+ or Ia- L cells, whereas no inhibition was seen with either Ia+ or Ia-B lymphoma cells. We conclude from these studies that LFA-1 plays a critical role in mitogen-induced activation of both T cell subsets by promoting both T-AC and T-T interactions. Although anti-L3T4 can inhibit T cell activation in the absence of the recognition of Ia, the mechanism of inhibition and the proposed target molecule for L3T4 on the AC or the T cell have not been determined in our studies. A number of different models for the function of this cell surface antigen are discussed.

Animals↗

Characterization and partial purification of a specific interleukin 2 inhibitor.

To investigate the mechanisms that regulate the action of interleukin 2 (IL 2) and possibly limit its activity, we screened supernatants of mouse spleen cell cultures which had been stimulated with concanavalin A (Con A) for their ability to inhibit IL 2-mediated proliferation of a cloned IL 2-dependent line. Inhibitory activities with m.w. of 10,000 to 12,000 and 60,000 to 80,000 daltons could be identified in supernatants of both L3T4+ and Ly-2+ T cells, but not in supernatants of Con A or lipopolysaccharide-stimulated B cells. Maximal inhibitory activity was observed after 3 to 4 days of stimulation, and this inhibitory activity could be overcome by increasing the stimulatory concentration of IL 2. When the factor was further purified by reverse-phase high pressure liquid chromatography, it eluted as a single peak with an m.w. of 11,000 to 12,000 daltons which inhibited IL 2- but not IL 3-dependent proliferation. The mechanisms by which this new lymphokine might play in the control of the clonal expansion of T lymphocytes are discussed.

Animals↗

Simulating refractive errors: source and observer methods.

There are two principal methods of simulating refractive errors. Either the retinal image can be defocused by an optical system, usually a positive lens, placed in front of an observer's eye (observer method), or the source of the retinal image can be defocused as it is projected onto a screen or photograph (source method). There are significant differences between the two methods, differences that make it difficult to compare results. However, the source method, which is the more artificial, seems to be superior for a number of reasons. The results of these two methods can be compared using a common or interchangeable parameter for specifying the level of defocus. A convenient parameter is the size of the defocused image of a point, measured either in image space (linear or angular diameter on the retina) or in object space (angular diameter of the blur disc projected back into object space), with the angular diameter measured from the respective nodal point of the eye. Methods of measuring the angular blur-disc diameter for both methods are discussed and the validity of the formula omega = D delta L, is investigated, where omega is the angular diameter of the blur disc, D is the observer's pupil diameter, and delta L is the dioptric defocus.

Humans↗