End-stage renal disease among Asians.
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Biomedical subjects
Publications and source records attributed to C S Li.
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Earthworm shock secretion contains a 20-kDa vomeronasally mediated chemoattractive protein for garter snakes. Both the ligand-receptor binding and the chemoattractivity of ES20 are Ca(2+)-dependent. When ES20 binds to its G-protein-coupled receptors in the vomeronasal epithelium, the inositol 1,4,5-trisphosphate (IP3) level is increased, but the level of cAMP is reduced. Furthermore, forskolin-stimulated levels of cAMP are completely blocked by ES20-receptor binding or by Ca2+ alone and the effect of calcium ions can be nullified by EGTA. Previously, we hypothesized that the decrease in cAMP was due to activation of a Ca(2+)-dependent phosphodiesterase. In the present study, we provide evidence that the decrease in cAMP is due mainly to the regulation of adenylate cyclase (AC) activity by Ca2+ or is indirectly mediated by ES20. Results obtained with intact vomeronasal sensory epithelium suggest that the binding of ES20 to its receptors facilitates generation of IP3 which mobilizes intracellularly sequestered Ca2+, resulting in an increase of cystosolic Ca2+. A further increase in cytosolic Ca2+ occurs through Ca2+ influx from extracellular sources. Garter snake vomeronasal AC does not require calmodulin for its activity and shows a biphasic response to increasing concentrations of Ca2+; its activity is modulated both positively and negatively by this bivalent cation.
These studies determined whether deficits in reproductive behavior observed in streptozotocin (STZ)-induced diabetic female rats are caused by hyperglycemia or loss of insulin. Female Sprague-Dawley rats were ovariectomized and made diabetic by a single ip injection of STZ (75 mg/kg). Reproductive behavior was measured 12 days after the onset of hyperglycemia following the injection of estrogen and progesterone in doses known to restore reproductive behavior in nondiabetic rats. Rats in which STZ produced diabetes showed significantly reduced receptive and proceptive sexual behaviors. Normalization of blood glucose levels either by restricting diet or by phlorizin treatment failed to restore reproductive behavior in diabetic animals. However, even doses of insulin which were not fully effective in correcting peripheral hyperglycemia were able to prevent the STZ-induced behavioral deficit. No changes in general activity were observed in any experimental group as assessed by open field activity. The density of the norepinephrine transporter, as measured by [3H]nisoxetine binding, was reduced in the cortex but not in the brain stem, hypothalamus, or hippocampus of diabetic animals. Insulin treatment prevented the loss of cortical [3H]nisoxetine binding, and even partial normalization of blood glucose restored cortical [3H]nisoxetine binding to control levels. These findings suggest that diabetes-induced reproductive deficits are due to hypoinsulinemia and cannot be corrected simply by the normalization of blood glucose, whereas reductions in the density of cortical norepinephrine transporter result from hyperglycemia.
We developed a quantitative RNAse protection assay for alpha 2A/D-adrenoceptor messenger RNA in rats to test the hypothesis that decreases in cortical alpha 2-adrenoceptor binding observed following estrogen treatment of ovariectomized rats correlate with reduced levels of messenger RNA encoding the predominant alpha 2-adrenoceptor subtype expressed in cortex. Estradiol treatment for 48 h reduced cortical alpha 2A/D-adrenoceptor messenger RNA by approximately 50% when compared to ovariectomized, oil-treated control animals. Estradiol down-regulation of alpha 2A/D-adrenoceptor messenger RNA was accompanied by a significant decrease in cortical alpha 2-adrenoceptor density, as measured by 3H-RX821002 binding. Estrogen treatment did not alter alpha 2A/D-adrenoceptor messenger RNA or alpha 2-adrenoceptor binding in female rat hypothalamus-preoptic area. This study provides the first evidence that estradiol regulates expression of postsynaptic alpha 2-adrenoceptors in female rat frontal cortex, suggesting a possible molecular substrate for hormonal modulation of cognitive function.
The effects of excitatory amino acid (EAA) receptor antagonists in blocking the synaptic transmission between gustatory fibers of the chorda tympani (CT) nerve and taste-responsive neurons within the nucleus of the solitary tract (NST) were examined electrophysiologically in urethan-anesthetized hamsters. Single neurons in the NST were recorded extracellularly and drugs were microinjected into the vicinity of the cell with the use of a multibarrel pipette assembly. The activity of each cell was recorded in response to lingual stimulation with 0.032 M NaCl, 0.032 M sucrose, 0.0032 M citric acid, 0.032 M quinine hydrochloride, and/or 25 microA anodal current pulses. Once a cell was identified as a taste-responsive neuron, one or more EAA receptor antagonists were administered by microinjection. Approximately 27 nl of 50 mM kynurenic acid (KYN), a broad-spectrum EAA receptor antagonist; 0.5 or 2.0 mM DL-2-amino-5-phosphonovalerate (APV), an N-methyl-D-aspartate (NMDA) receptor antagonist; 0.05 or 0.5 mM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), an alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor antagonist; or phosphate-buffered physiological saline was applied to the neuron. Responses to chemical stimulation of the anterior tongue were obtained before and after drug administration and again after recovery; responses to anodal current stimulation (0.1 Hz) were obtained continually throughout the drug administration protocol. Microinjection of KYN completely and reversibly abolished responses elicited by both anodal current and chemical stimulation of the anterior tongue. The excitatory responses of cells in the NST to chemical and electrical stimulation of the anterior tongue were also completely and reversibly blocked by CNQX, implicating the involvement of an AMPA/kainate receptor. Microinjection of APV was generally less effective and partially reduced the responses of some taste-responsive NST cells to chemical stimulation of the anterior tongue. There were no effects following microinjection of a 27-nl bolus of phosphate-buffered saline. None of these EAA receptor antagonists had a differential effect on responses to different taste stimuli. The responses to all tastants were completely blocked by both KYN and CNQX; there was no apparent relationship between the response to any particular tastant and the limited effects of APV. These data implicate glutamate as an excitatory neurotransmitter between CT gustatory fibers and taste-responsive NST cells and suggest that it acts primarily on AMPA/kainate receptors, with some contribution from NMDA receptors. This conclusion is strengthened by other data obtained from in vitro slice preparations, which show that responses of cells in the rostral NST to solitary tract stimulation are blocked by both NMDA and AMPA/kainate receptor antagonists.
This study validates Ing's partial dialysate collection method, which employs proportionate collection using a side tube capped with a small-gauge plastic needle. The urea nitrogen and creatinine levels of the small representative fraction of spent dialysate collected in the above fashion are undistinguishable from those obtained from the total spent dialysate. The estimated urea nitrogen removed during hemodialysis using this approach is similar to that using the total dialysate collection method; Ing's method is simple and useful in quantifying the dialysis dosage and in its assessment of the nutritional status of patients on hemodialysis.
We report on 352 cadaveric kidney transplants and 294 living related transplants performed over a 25-yr period among the Chinese population of Hong Kong. There is a marked preference for transplanting male patients, especially from living donors, and we argue that this represents a cultural phenomenon within the Chinese population. The 10-yr graft survivals for related and cadaveric transplants are 86.2% and 67.4%, respectively. These figures are appreciably higher than corresponding figures in Caucasian populations. We show beneficial effects of using cyclosporin A, minimizing the cold ischemia time and avoiding very young and very old donors. There is a clear benefit of transplanting kidneys with zero or one mismatched HLA antigen against the recipient but no stepwise decrease in outcome as the number of mismatched antigens increases. There is close concordance between the outcome of living related grafts with zero, one, and two mismatched haplotypes against the recipient and no observable benefit of haplotype matching. We show that Chinese renal transplant recipients in other centers also have better long-term graft outcome than Caucasians, both for cadaveric and living related transplants. We draw attention to the existence of a detrimental "race effect" in other studies when Black recipients are compared with Caucasians and consider whether an enhancing race effect exists for Chinese or whether the better outcome reflects different underlying diseases in Chinese.
BACKGROUND: The group 7 mite allergens react with IgE in 50% of sera from allergic patients. OBJECTIVE: To determine the molecular and antigenic characteristics and heterogeneity of Der f 7 in mite extracts. METHODS: Monoclonal antibodies (MoAbs) produced from mice immunized with recombinant Der f 7 were examined for crossreactivity to Der p 7 and then used for immunoblotting of 1 and 2-D gel electrophoresis. Deglycosylation was studied with N-glycosidase-F and N-terminal sequencing by Edman degradation. The epitopes of the monoclonal antibodies were compared by cross-inhibitory immunoassays. RESULTS: Immunoblotting of D. farinae extracts with all the anti Der f 7 MoAbs showed major reactivities at 31, 30 and 25 kDa. The strongest immunostaining was at 25 kDa which contrasted with Der p 7 where the 31 and 30 kDa bands were strongest. The relative strength of staining however varied between extracts. The 31 and 30 kDa components were glycosylation products of the 25 kDa form which had the N-terminal sequence predicted from cDNA analysis. Two MoAbs stained an 18 kDa band consistent with a degradation product. The 2-D gels showed that different components with pIs from 5.6-6.4. Both species-specific and Der p 7 crossreactive MoAbs were produced and a two-site ELISA assay for detecting group 7 allergen was developed with MoAbs recognizing different epitopes. CONCLUSIONS: Der f 7 has been defined by its natural N-terminal sequence and MoAbs. It apparently exists as different glycosylation and degradation products in mite extracts, the relative abundance of which differs with different preparations. A two-site ELISA to measure the allergen was developed.
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The present study was designed to test the hypothesis that preferential nuzzling of unfamiliar conspecific odors by male opossums is vomeronasally mediated. Opossums were presented with vials containing their own odors (Own) and vials with odors from unfamiliar conspecifics (Novel) both before and after (Expt. 1) or only after (Expt. 2) vomeronasal nerve (VNNX) or sham (Sham) surgery. Nuzzling duration was greater for Novel before (Expt. 1) and after (Expts. 1 and 2) surgery both in VNNX and Sham animals, indicating that a functional vomeronasal system is not necessary for the differential nuzzling of novel odors. In contrast, differential scent marking of Novel was lost following VNNX, but not following sham surgery. Since VNNX lesions disrupt differential marking behavior but, not differential nuzzling, it is possible that different components of conspecific odors guide these two chemosensory behaviors and that these components may be detected by different sensory systems. Vomeronasal nerve lesions, confirmed histologically, resulted in the loss of the beta-NADPH-dependent reaction product from the accessory olfactory bulbs (AOB). The pattern of staining with 4 lectins, soybean agglutinin (SBA), Phosphocarpus tetragonolobus (PCT), Vicia villosa agglutinin (VVA), and Griffonia simplicifolia lectin I-isolectin B4 (GS I-B4) remained unchanged in the AOB following vomeronasal nerve lesions, although the size of the AOB appeared to decrease in the VNNX animals.
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We prospectively monitored the clinical outcome of 89 curled, double-cuff peritoneal catheters (PC) implanted by surgeons over one year. Thirty-six cases (40%) were supported with hemodialysis (HD) (group A) and 53 cases (60%) were supported with weekly intermittent peritoneal dialysis (IPD) (small exchange volume with a cycler) (group B) for four weeks before commencing continuous ambulatory peritoneal dialysis (CAPD). PC-related complications between the two groups were compared. Ten cases failed to complete the six-month observation period (8 died, 1 received kidney transplant, and 1 defaulted follow-up),Total experience accumulated was 494 patient-months (195 patient-months in group A, 299 patient-months in group B). The incidence of pericatheter leakage (group A vs group B) was significantly higher in group B (0% vs 13%, p < 0.05). There were no significant differences in the incidence of other PC-related complications, removal of PC, and mortality rate in the two groups. The incidence of pericatheter leakage was significantly higher in diabetic patients (71% vs 22%, p < 0.05), and group B patients with leakage had a higher incidence of external cuff erosion 57% vs 7%, p < 0.005) and delay in CAPD training (71% vs 7%, p < 0.005). We conclude that both HD and IPD are equally safe renal replacement therapies in the break-in period, while patients supported with IPD had a higher incidence of pericatheter leakage, which was associated with other catheter-related morbidities including external cuff erosion and delay in CAPD training.
The recent discovery of an alternative form cyclooxygenase (cyclooxygenase-2, COX-2), which has been proposed to play a significant role in inflammatory conditions, may provide an opportunity to develop anti-inflammatory drugs with fewer side effects than existing non-steroidal anti-inflammatory drugs (NSAIDs). We have now identified 6-[(2,4-difluorophenyl)-thio]-5-methanesulfonamido-1-indanone++ + (20) (L-745,337) as a potent, selective, and orally active COX-2 inhibitor. The structure-activity relationships in this series have been extensively studied. Ortho- and para-substituted 6-phenyl substitutents are optimal for in vitro potency. Replacement of this phenyl ring by a variety of heterocycles gave compounds that were less active. The methanesulfonamido group seems to be the optimal group at the 5-position of the indanone system. Compound 20 has an efficacy profile that is superior or comparable to that of the nonselective COX inhibitor indomethacin in animal models of inflammation, pain, and fever and appears to be nonulcerogenic within the dosage ranges required for functional efficacy. Although 20 and its oxygen linkage analog 2 (flosulide) are equipotent in the in vitro assays, compound 20 is more potent in the rat paw edema assay, has a longer t1/2 in squirrel monkeys, and seems less ulcergenic than 2 in rats.
Chronic phencyclidine (PCP) administrations in postnatal rats produce long-term behavioral changes. Here we report the effects of repeated postnatal PCP treatment on [3H](+)pentazocine binding in juvenile rats. Saturation analyses of the binding data showed no significant difference in any of the binding characteristics between chronic PCP-related rats and saline-treated controls suggesting that mechanisms other than alterations in sigma1 binding underlie the behavioral effects of repeated postnatal PCP administration in immature rats.
Cholesterol embolization syndrome (CES) usually occurs after the performance of invasive vascular procedures. With the frequent use of thrombolytic agents, an increasing number of reported cases of renal CES attributed to the use of such agents has appeared. In most of these reports, the diagnosis was made on the basis of either clinical presentations or skin biopsy. We report a patient who developed acute renal failure as a result of histologically proven renal CES occurring after the use of streptokinase for the treatment of an acute myocardial infarction. The acute renal failure later became chronic; consequently, the patient was placed on continuous ambulatory peritoneal dialysis. Although the prognosis of renal CES has been described to be poor, our patient regained enough of his renal function 8 months after the onset of renal failure to make it possible to discontinue the dialytic therapy.
Systemic disorders, often immune in nature, can sometimes be associated with the presence of thymic pathology. Thymic enlargement due to lymphoid hyperplasia or thymoma is a common occurrence in patients with myasthenia gravis. In patients with pure red cell aplasia, at least 10% to 15% of patients are found to have thymoma, usually of spindle cell or medullary type. Pure red cell aplasia with demonstrable thymic enlargement due to lymphoid follicular hyperplasia is distinctly unusual, and has not been previously reported. The authors report such a case developing in a patient with end-stage renal failure maintained on hemodialysis and erythropoietin therapy. Because the red cell aplasia resolved after thymectomy, the disease process was considered etiologically related to the reactive lymphoid hyperplasia.
One hundred children with hyperkinetic syndrome were treated by using Tiaoshen Liquor (TL) consisted of Chinese herbal drugs. After the treatment, the behavior grading lowered greatly, their attention was improved, and their academic records raised. The total effective rate reached 94%. The results of the animal experiments showed that TL could reduce the spontaneous activities of the healthy mice, thus lowering remarkably the spontaneous activities in the mice with hyperkinetic behavior caused by taking scopolamine; reinforce the learning memory in the healthy mice; and improve in different degrees the learning memory of the mice with dysmnesia caused by administering scopolamine, sodium nitrite and alcohol respectively, which indicate that the therapeutic mechanism of TL for this syndrome was probably related to the improvement of information transfer function of the cholinergic neuron synapses of central nervous system and to the enhancement of hypoxia tolerence of the cerebral tissues.