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Biomedical subjects

J Hui

Publications and source records attributed to J Hui.

At least 55 records · Page 3Linked to original sources

[In situ observation of the relationship between apoptosis and proliferation in large bowel carcinoma and its precancerous lesion].

OBJECTIVE: To investigate action of apoptosis in tumorigenesis by observation of the relationship between apoptosis and proliferation. METHOD: Using terminal deoxynucleotidyl transferase-mediated dUTP niok end labelling (TUNEL) technique, PCNA immunohistochemical staining, and HE staining, we observed the density and distribution of apoptotic cells, proliferating cells and mitotic cells in situ in 15 normal mucosa, 32 villous adenoma and 33 papilloid adenocarcinoma of large bowel. RESULTS: The zone of apoptotic cells located in superficies and zone of proliferating cells in base in normal mucosa. These characteristics of distribution were lost in villous adenomas and papilloid adenocarcinomas of large bowel. The density of apoptotic cells in villous adenomas was significantly higher than that in normal mucosa and carcinomas. The density of apoptotic cells lowered and the density of proliferating cells rose in villous adenomas. Comparison of villous adenoma with papilloid adenocarcinoma, showed that apoptotic cells decreased and proliferating cells increased significantly. CONCLUSIONS: Through selectivity, the cells have highly proliferative ability prodominanted, resulting in malignant transformation. This phenomenon was named as a selective proliferation of cells.

Adenocarcinoma, Papillary↗

Correlations between familial refractive error and children's non-cycloplegic refractions.

We examined the spherical equivalent refractions of 237 subjects who had been seen four or more times in a longitudinal study of refractive development in normal children. We employed both photorefraction and autorefraction using a Canon R1 autorefractor. We performed an analysis of variance (F-test for Lack of Fit) to determine the significance of a linear regression in fitting these refractions against three different measures of familial refractive status. One measure included only the number of myopic parents, a second took into account the number of hyperopic parents, and a third included the refractive states of extended genetic relatives. We found no significant correlation between photorefractive data and familial refractions; however, we did find significant, albeit weak, correlations between all measures of familial refractive status and infrared autorefractions of their children. A linear relationship between autorefractive data and overall familial refractive state was found to be most significant. Linear regression of children's autorefractions against a measure of parental myopia and hyperopia was less significant, while a linear model fitting only a measure of parental myopia was least significant, in addition to showing other non-linear trends. We attribute the failure to find a significant correlation between parent and offspring refractions using children's photorefractive data to vignetting by the apparatus and to the short distance of the fixation target. We believe the significant correlation patterns found with the autorefractor reflect the inheritance patterns of parental and familial refractive states.

Adolescent↗

L-NMMA blocks carbachol-induced increases in cGMP levels but not decreases in tension in the presence of forskolin in rabbit papillary muscles.

OBJECTIVE: The purpose of the present investigation was to determine whether stimulation of the nitric oxide synthase pathway contributes to the muscarinic receptor-mediated elevation in cGMP levels and reversal of the positive inotropic response to the adenylyl cyclase activator forskolin in rabbit papillary muscles. METHODS: Intact rabbit papillary muscles suspended under tension in isolated tissue baths were incubated in the absence or presence of the nitric oxide synthase inhibitor L-NG-monomethyl arginine (L-NMMA) and then treated with forskolin followed by the muscarinic agonist carbachol. The developed tension of the preparations was monitored during their exposure to drug. Papillary muscles were then frozen and subsequently assayed for cGMP levels by radioimmunoassay. Tension and cGMP levels were also measured in some papillary muscles treated with forskolin followed by sodium nitroprusside. RESULTS: Incubation of papillary muscles with L-NMMA completely blocked increases in cGMP levels produced by carbachol, but had no effect on the reversal by carbachol of the increase in tension in response to forskolin. Sodium nitroprusside also caused a marked elevation of cGMP levels in rabbit papillary muscle, but had no significant effect on the forskolin-induced increase in tension. CONCLUSIONS: These data demonstrate that activation of muscarinic receptors results in increases in cGMP levels largely through the nitric oxide synthase pathway in rabbit papillary muscles. However, the cGMP produced through this pathway or by sodium nitroprusside does not appear to contribute to the reversal of the positive inotropic response to forskolin.

Animals↗

High frequency oscillatory ventilation in newborns with idiopathic persistent pulmonary hypertension.

Three consecutive term infants diagnosed as suffering from idiopathic persistent pulmonary hypertension of the newborn (PPHN) were tried on high frequency oscillatory ventilation (HFOV) after failure of conventional mechanical ventilation (CMV). All experienced a significant improvement in oxygenation. All three infants survived. HFOV was utilised in a fourth term infant initially diagnosed as having idiopathic PPHN with an immediate benefit. This infant subsequently died and was found at autopsy to have a lethal congenital maldevelopment of pulmonary microcirculation. No serious adverse effects were encountered with HFOV in contrast to the use of pharmacologic agents where hypotension was a serious problem. A therapeutic trial of HFOV is simple and efficient, and would not cause undue delay in the commencement of other rescue therapy should it prove unsuccessful. We predict HFOV will replace non-specific vasoactive agents as the standard first line alternative to CMV for the treatment of idiopathic PPHN.

Female↗

Digoxin disposition in elderly humans with hypochlorhydria.

Digoxin (D3) metabolism is partially mediated by the gastrointestinal tract via acid hydrolysis of digitoxose sugar moieties and bacterial reduction of the lactone. The hypothesis that hypochlorhydria influences digoxin disposition was tested in six normochlorhydric (NC) and four hypochlorhydric (HC) subjects. D3 tablets were administered daily for 19 to 28 days, and quantitative urine and fecal samples were collected over the last 3 days (steady state). Samples were analyzed for D3 and its extractable metabolites by fluorescence-derivatization HPLC. Excretion of D3 in urine increased from 37% of the dose in NC to 46% in HC, whereas excretion of D3 in feces decreased from 29 to 14%. These changes were statistically significant (P < .05) and consistent with decreased hydrolysis of D3 by stomach acid and increased intestinal metabolism in HC. In each subject, D3 was added to anaerobic cultures of both feces and jejunal fluid. Digoxin was reduced in all but two of the fecal incubates, and was not reduced in any jejunal fluid incubates. Because dihydrodigoxin (DHD3) was found in only two hypochlorhydric subjects, in vitro measures of bacterial reduction of D3 were not predictive of in vivo excretion of reduced metabolites. Sugar-hydrolyzed, reduced metabolites were not found in any subjects. It is concluded that D3 disposition is altered by hypochlorhydria, and that an understanding of the metabolic mechanisms requires further study.

Achlorhydria↗

Polysaccharides in fungi. XXXII. Hypoglycemic activity and chemical properties of a polysaccharide from the cultural mycelium of Cordyceps sinensis.

Crude polysaccharides were obtained from a hot-water extract and alkaline extracts of the cultural mycelium of Cordyceps sinensis. They showed significant activity in normal mice and streptozotocin-induced diabetic mice as a result of intraperitoneal (i.p.) injection. A crude polysaccharide (CS-OHEP) obtained from 5% sodium hydroxide extract slightly lowered the plasma glucose level in normal mice by oral (p.o.) administration. A neutral polysaccharide (CS-F30) exhibited higher hypoglycemic activity than its crude polysaccharide (CS-OHEP), exhibited by i.p. injection, and it significantly lowered the glucose level by p.o. administration (50 mg/kg). However, it hardly affected the plasma insulin level in normal mice. CS-F30 ([alpha]D + 21 degrees in water) is composed of galactose, glucose and mannose (molar percent, 62:28:10), and its molecular weight is about 45000.

Animals↗

Comparison of three nonradioisotopic polymerase chain reaction-based methods for detection of human immunodeficiency virus type 1.

Three nonradioisotopic polymerase chain reaction (PCR)-based detection techniques were evaluated for sensitivity and specificity in detecting human immunodeficiency virus type 1 (HIV-1) proviral DNA in peripheral blood mononuclear cells. The Roche prototype HIV-1 PCR assay, the Du Pont enzyme-linked oligonucleotide sandwich assay (ELOSA), and the Gen-Probe hybridization protection assay (HPA) were compared with a standard radioisotopic oligonucleotide solution hybridization (OSH) technique. A panel of 111 well-characterized clinical samples that included peripheral blood mononuclear cells from 48 healthy, low-risk, HIV-1 antibody-negative subjects, 24 antibody-positive subjects with stable CD4 counts of less than 200/mm3, and 39 antibody-positive subjects with stable CD4 counts of greater than 800/mm3 were studied. Each method demonstrated good specificity, ranging between 96 and 100%; those of the OSH and ELOSA (Du Pont) were 100%, those of the HPA (Gen-Probe) were 100% with one probe and 96% with the other probe, and that of the HIV-1 PCR assay (Roche) was 96%. Sensitivities ranged from 96 to 100% for the low-CD4-count group, with the OSH, the HIV-1 PCR assay (Roche), and the HPA (Gen-Probe) all attaining a sensitivity of 100%. For the high-CD4-count group, sensitivities ranged from 69 to 97%, with the OSH attaining a sensitivity of 97% and the HPA attaining sensitivities of 97% with one probe and 95% with the other probe. These data indicate that the nonradioisotopic techniques are sensitive and specific for the detection of HIV-1 proviral DNA in clinical samples.

Base Sequence↗

Inhibitors of the protease from human immunodeficiency virus: design and modeling of a compound containing a dihydroxyethylene isostere insert with high binding affinity and effective antiviral activity.

The peptidomimetic template and the dihydroxyethylene isostere insert that were applied successfully to the design of renin inhibitors have been extended to the related protease from human immunodeficiency virus (HIV). The present report describes the structure-activity study leading to the identification of an inhibitor with a Ki of less than 1 nM for the HIV type-1 protease (compound II). This compound, containing a diol insert, is highly effective in blocking polyprotein processing in in vitro cell culture assays. Results obtained from kinetic analysis, studies of the stereochemistry of the insert, and modeling have led to insights as to the requisites involved in the active site-inhibitor interaction.

Amino Acid Sequence↗

[Ectopic hormone producing cells in non-small cell lung carcinoma (non-SCLC) and heterogeneity of lung cancer].

68 cases of non-SCLG were investigated by immunohisto-chemical technique to detect ectopic hormone producing cells and to study the heterogeneity of non-SCLC. Histologic heterogeneity was observed in 11 of 68 non-SCLC and 24 (35.3%) cases displayed hormone immunoreactivity. Ten cases were positive for NSE. More than one type of hormone producing cells could be detected in 11 tumors. Both neutral and acid mucoproteins in variable quantities were observed in 17 tumors that contained the hormone or NSE producing cells. The results indicate that there is functional heterogeneity in non-SCLC, and all types of lung carcinoma may have a common cellular origin.

Adult↗

Ultrasonic tissue characterization of blood clots.

Ultrasonic tissue characterization based on an analysis of the power spectrum of backscattered signals obtained with ultrasound was used to distinguish morphologic components of blood clots. The three morphologic features for which discrimination was attempted were loose fibrin, red-cell, and dense fibrin clots. The UTC was able to distinguish the morphologic blood components tested. This in vitro work was based on the analysis of parameters related to ultrasound-tissue interaction and on inferences related to the physical properties of scatterer properties (scatterer size, scatterer concentration, and ratio of scatterer to medium acoustic impedances). The ability to distinguish these blood-clot components suggests that UTC may be able to distinguish red from white thrombi and to assess the structures and changes within thrombi associated with the age of the thrombus, their mechanical properties, and treatment monitoring.

Blood Coagulation↗

Dimerization and activation of porcine pancreatic phospholipase A2 via substrate level acylation of lysine 56.

The porcine pancreatic phospholipase A2-catalyzed hydrolysis of the water-soluble chromogenic substrate 4-nitro-3-octanoyloxybenzoate shows an initial latency phase similar to the one observed in the hydrolysis of aggregated phospholipids by the same enzyme. We report here that during the latency phase the enzyme undergoes a slow, autocatalytic, substrate-level acylation whereby in a few of the catalytic events the scissile octanoyl group of the substrate, normally transferred to water, is transferred to the epsilon-amino group of lysine 56. The N epsilon 56-octanoylphospholipase shows a strong tendency to dimerize in solution and thus may be separated from the monomeric native enzyme by gel filtration. Octanoylation of Lys-56 activates the enzyme some 180-fold toward 4-nitro-3-octanoyloxybenzoate and more than 100-fold toward monolayers of 1,2-didecanoyl-sn-glycero-3-phosphocholine. Acylation also attends the enzymatic hydrolysis of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine with the incorporation of 1 eq of palmitate. Kinetic analysis of the early phase of reaction with 4-nitro-3-octanoyloxybenzoate shows that in this initial step the rate of activation is first order with respect to enzyme and substrate. A much more rapid, autocatalytic activation occurs in the later phases of the reaction where the activation of the enzyme is catalyzed by the activated enzyme itself. These findings with porcine pancreatic phospholipase A2, together with those relative to a snake venom enzyme monomer (Cho, W., Tomasselli, A. G., Heinrikson, R. L., and Kézdy, F. J. (1988) J. Biol. Chem. 263, 11237-11241), strongly support the proposal that interfacial activation of monomeric phospholipases is due to substrate-level autoacylation resulting in fully potentiated dimeric enzymes.

Acylation↗

A structural model to explain the partial catalytic activity of human prorenin.

Human prorenin, secreted from a Chinese hamster ovary cell line transfected with the cDNA for preprorenin, has been purified in mg quantities by a novel single-step procedure. The method takes advantage of reversible acid activation as a means of generating active prorenin that may be bound and eluted from an affinity column for renin. Analysis of the prorenin so purified revealed that it contained about 80% intact zymogen; the remaining 20% comprised a mixture of various prorenin derivatives truncated in the prosegment, and a small amount of renin. After exposure to 37 degrees C and pH 7.5, the refolded, partially active preparation was passed once more over the affinity column to remove renin and any truncated prorenin forms that were still active and that were, therefore, again retained by the column. Over a period of several hours, refolded and inactive prorenin not bound to the column slowly regains 5% to 10% renin activity, even when maintained under conditions that are optimal for zymogen inactivation. This activity is observed toward both model peptide substrates and natural human angiotensinogen. On the basis of these findings, we propose a model in which, under physiological conditions, a small amount of open, active prorenin is in equilibrium with a predominant, closed, and inactive form of the zymogen. Support for the model is provided by binding studies with a strong renin inhibitor that displaces the equilibrium entirely to a 1:1 zymogen:inhibitor complex. Limited cleavage of prorenin by several different proteinases has provided a number of fully active renin derivatives with varying N-terminal sequences. Results thus obtained, together with analysis of prorenin and its truncated forms bound, or not bound, to the affinity column under a variety of conditions, suggest that the propeptide region, -Arg-Ile-Phe-Leu-Lys- (positions 10P-14P), is essential for the reversible refolding of the prosegment that leads to zymogen inactivation.

Binding Sites↗

Comparison of theoretical scattering results and ultrasonic data from clinical liver examinations.

A theoretical analysis of soft-tissue ultrasonic scattering has been used to formulate specific results describing spectral parameters for tissue characterization. Results are applicable to clinical liver examinations. Three spectral parameters are mathematically expressed in terms of acoustic attenuation and the effective sizes, concentrations, and relative acoustic impedances of tissue scatters. Results from a clinical data base are shown to agree well with analytical results for each spectral parameter. Agreement is found for: spectral shapes; effects of attenuation; and correlations between parameters. Images of three spectral parameters are presented and their gray-scale features are evaluated with reference to analytical results.

Humans↗

Inaccessibility of tryptophan residues of recombinant human renin to quenching agents.

The fluorescence quenching of the three tryptophan residues of recombinant human renin was determined using ionic and penetrating quenchers. Tryptophans 44,200, and 312 of recombinant human renin were found to be totally inaccessible to the ionic quenchers cesium and iodide and only partially accessible to the penetrating quencher acrylamide. The renin had a fluorescence emission maximum at 325 nm which was made up of three separate components as determined by second derivative spectroscopy. These data are in accord with solvent accessibility calculations from three-dimensional models of human renin but differ from findings published previously from similar analysis of mouse submandibular gland renin (Quay, S. C., Heropoulous, A., Commes, K., Dzau, V. J. (1985) J. Biol. Chem. 260, 15055-15058), which is 68% identical in sequence to human renin.

Acrylamide↗

Digoxin and metabolites in urine and feces: a fluorescence derivatization--high-performance liquid chromatographic technique.

A high-performance liquid chromatography method is described for the determination of digoxin and its metabolites digoxigenin, digoxigenin monodigitoxoside, digoxigenin bis-digitoxoside and dihydrodigoxin (20S and 20R) excreted in urine and feces. The urine sample or fecal supernatant is extracted with methylene chloride in the presence of digitoxigenin or digitoxin as internal standard. Pre-column derivatization is achieved using 1-naphthoyl chloride with subsequent separation of the derivatized compounds on either a normal- or reversed-phase system with fluorescence detection. Recoveries for digoxin and all metabolites from fecal samples were in the range 60-74%, which is comparable to that previously determined for urine samples. Standard curve data revealed linearity over a wide range of concentrations. Coefficients of variation for the analysis were less than 10% for all compounds over a range of 5-125 ng per ml urine and 10-250 ng per 200 mg feces. Peaks for digoxin and metabolites in urine and feces were obtained when human excreta were analyzed.

Chromatography, High Pressure Liquid↗

Reduction of digoxin to 20R-dihydrodigoxin by cultures of Eubacterium lentum.

The anaerobic bacterium Eubacterium lentum, a common constituent of the intestinal microflora, inactivates digoxin by reducing the unsaturated lactone ring. Reduction of the cardiac glycoside by growing cultures of E. lentum ATCC 25559 proceeded in a stereospecific manner, with the 20R-dihydrodigoxin constituting more than 99% of the product formed. This is in contrast to the 3:1 ratio of 20R and 20S epimers formed in the chemical catalytic hydrogenation. Formation of the reduced glycosides proceeded quantitatively when an overall concentration of 10 micrograms/ml was added to the cultures. E. lentum did not hydrolyze the digitoxose sugars from C-3 of the parent glycoside. However, the synthetically prepared sugar-hydrolyzed metabolites (digoxigenin, digoxigenin monodigitoxoside, and digoxigenin bisdigitoxoside) were reduced to the corresponding dihydro metabolites. Repetition of the experiments with a feces sample from a volunteer who was known to be a converter of digoxin to dihydrodigoxin gave results identical to those obtained with pure E. lentum cultures.

Chromatography, High Pressure Liquid↗

Current status of external counterpulsation.

This article traces the development of external counterpulsation from its beginnings to the present. Initially, counterpulsation was carried out by cannulating the femoral artery. The hemodynamic goals were to reduce the afterload of the left ventricle, and to raise or augment the diastolic pressure. This gave rise to the term "counterpulsation." The intra-aortic balloon is capable of producing these salutary effects because of its proximity to the outlet of the left ventricle. The same hemodynamic effects can be obtained by external counterpulsation. However, one must produce a negative pressure during cardiac systole, and ensure that this is applied to the lower extremities. The only clinical study in which this was done was in the treatment of patients in cardiogenic shock by Soroff and colleagues. The results of the clinical studies reviewed are all suggestive of benefits derived from external counterpulsation in a variety of clinical settings. These studies suggest the following avenues for improvement in the equipment used to carry out external counterpulsation: 1. Inclusion of the vascular bed of the buttocks to be subjected to the external pressures, as advocated by Zheng. 2. Inclusion of a negative pressure blanket, as advocated by Soroff. 3. Further investigation of graded-sequential external counterpulsation, using the buttocks and negative pressure. 4. Application of external counterpulsation earlier in cardiogenic shock and for at least 4 hours in acute myocardial infarction. Our evaluation is that this method has not been studied in a way that demonstrates its full potential. We feel that it is on the threshold of being shown to be useful in all of the clinical settings reviewed, and we hope that the necessary equipment will be created to allow investigators to establish its proper place in our therapeutic armamentarium.

Acute Disease↗