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Biomedical subjects

Y F Chen

Publications and source records attributed to Y F Chen.

At least 199 records · Page 11Linked to original sources

Use of the lectin from Amaranthus caudatus as a histochemical probe of proliferating colonic epithelial cells.

A newly isolated lectin, Amaranthus caudatus agglutinin (also called amaranthin or ACA), which binds to the Thomsen-Friedenreich antigen (T-antigen) and its sialylated variants, was used as a histochemical probe for proliferating cells in sections of human colonic tissues. Binding inhibition studies revealed that ACA binds to different sites on histological sections when compared to peanut agglutinin, which also recognizes the T-antigen. ACA bound selectively to the cells at the base of the colonic crypt [46 +/- 4% (SEM) of glands] which is the zone of proliferation in this tissue and preferentially labeled cytoplasmic and apical membrane glycoconjugates. Only 7 +/- 2% of the upper portions of the colonic crypts were labeled (P less than 0.001 compared to the base), and this was largely a result of extensive labeling in 2 of 23 samples studies. A marked increase in histochemical labeling by ACA was seen in adenomatous polyps and adenocarcinomas of the colon, in which 82 +/- 7 and 97 +/- 2% of the glandular units were labeled, respectively. Transitional mucosa and connective tissue adjacent to cancers were also labeled by ACA. Neuraminidase studies indicated that removal of sialic acid residues enhanced binding by peanut agglutinin, but not ACA, to glycoconjugates in cancer specimens. Specimens of colonic tissue from patients with familial adenomatous polyposis (FAP) were examined with ACA; 83 +/- 7% of adenomatous glands and 60 +/- 7% of glands in flat, normal-appearing tissue were labeled. Colonic tissues from persons at 50% risk for hereditary nonpolyposis colorectal cancer (HNPCC), FAP, and normal colons were studied and given "weighted average" labelling scores that ranged from 0-400 to accommodate variable intensity and distribution of labeling. Normal colons had a weighted average score of 65 +/- 33; FAP tissues had a score of 224 +/- 76 (P less than 0.001 compared to normal colon) and HNPCC tissues had a score of 74 +/- 70 (P less than 0.05 compared to normal colon). A group of five HNPCC cases had scores of 203 +/- 43 (P less than 0.001 compared to normal colon). ACA labels glycoconjugates in the proliferative region of normal human colonic epithelium and neoplastic lesions of the colon. The results of FAP and HNPCC tissues suggest that it may be useful for identifying foci of abnormal proliferation in familial colorectal cancer syndromes.

Adenocarcinoma↗

Activation of macrophages from aging mice by detoxified lipid A.

A detoxified derivative of endotoxic lipopolysaccharides (LPS), monophosphoryl lipid A (MPL), which is capable of inducing nonspecific resistance against several infectious organisms, was tested for its capacity to activate peritoneal macrophages (M phi) from young and immunodeficient aging BALB/c and C3H/HeN mice. Superoxide generation and hydrogen peroxide release by M phi from aging mice were elevated following intraperitoneal injection with 25 micrograms of LPS or MPL, although they did not reach the peak levels achieved in LPS or MPL-treated young mice. Nitroblue tetrazolium reduction (NBT) by peritoneal M phi from aging C3H/HeN mice treated with MPL was higher than that in control aging mice, equalling that from MPL-treated young mice. LPS, its toxic counterpart, however, failed to increase NBT reduction in either group. MPL enhanced lysozyme activity in M phi from both aging and young C3H/HeN mice above initial control levels. On the other hand, LPS suppressed lysozyme activity in M phi from young, but not aging mice. Phagocytosis of Candida albicans by M phi from BALB/c mice was increased in both groups when stimulated by MPL, but not LPS. Similarly, MPL enhanced the ability to kill Candida in both aging and young BALB/c mice. This effect was not seen with LPS. Thus, a detoxified derivative of LPS was found capable of activating the respiratory burst, NBT reduction, elevating lysozyme activity, as well as phagocytosis and killing of Candida in murine peritoneal M phi from both young and aging mice.

Aging↗

Insertions in the prion protein gene in atypical dementias.

A number of mutations have been demonstrated in the open reading frame (ORF) of the prion protein (PrP) gene in patients with familial Creutzfeldt-Jakob disease or Gerstmann-Sträussler syndrome. On the basis of detecting an insertion in the ORF of the PrP gene in a patient originally suspected to be suffering from familial Alzheimer-type dementia, we screened 101 individuals with atypical dementias for the known PrP gene mutations. Insertions were found in five individuals, whereas none of the other reported mutations in the PrP gene was detected in the present study. One of the five insertions was larger than that described previously, suggesting that the individuals with these mutations are unlikely to be all lineally related and that insertions in the PrP gene may not be uncommon in prion diseases.

Alzheimer Disease↗

Sexual dimorphism of blood pressure in spontaneously hypertensive rats is androgen dependent.

Intact male and female spontaneously hypertensive rats showed a progressive increase in blood pressure with growth; male attained systolic blood pressure levels of 244 +/- 6 mmHg, and females 205 +/- 3 mmHg at age 22 weeks. Orchidectomy at age 4 weeks significantly attenuated the systolic blood pressure elevation in the male (195 +/- 4 mmHg at age 22 weeks), but ovariectomy at age 4 weeks had no effect on the development of hypertension in the female. The pattern of development of hypertension in orchidectomized males was the same as that in intact and ovariectomized females. Administration of testosterone propionate to gonadectomized rats of both sexes conferred a male pattern of blood pressure development. These results indicate that the sexually dimorphic pattern of hypertension in the spontaneously hypertensive rat is androgen dependent, rather than estrogen dependent. Plasma norepinephrine levels did not differ between the sexes, nor were they altered by gonadectomy or testosterone replacement, suggesting that the higher blood pressures in the intact male and androgen treated male and female SHR are not dependent on increased sympathetic outflow in the established phase of hypertension. Stores of norepinephrine in the posterior hypothalamic region were significantly greater in intact male rats and testosterone treated rats of both sexes than in intact or ovariectomized females, and were higher in the pons of intact female rats than in all other groups. These alterations in central catecholamine stores were not correlated with blood pressure. Further study is needed to assess the functional significance of these androgen mediated alterations in posterior hypothalamic neurons as a determinant of the androgen mediated sexual dimorphism of blood pressure in the spontaneously hypertensive rat.

Androgens↗

Dietary Ca2+ prevents NaCl-sensitive hypertension in spontaneously hypertensive rats via sympatholytic and renal effects.

NaCl-sensitive spontaneously hypertensive rats (SHR-S) were used to test the hypotheses that dietary Ca2+ supplementation 1) prevents NaCl-sensitive hypertension via a sympatholytic mechanism, and 2) increases diuretic and natriuretic responses to acute volume loading. SHR-S and control WKY rats were begun on one of four diets at age 8 wk: control, high NaCl, high Ca2+, or high NaCl and high Ca2+. In SHR-S, dietary Ca2+ supplementation prevented the NaCl-induced increases in blood pressure and plasma norepinephrine concentrations, the reductions in anterior hypothalamic norepinephrine stores and turnover, and the secondary increases in alpha 2 adrenoceptor number. Thus, Ca2+ prevented NaCl-sensitive hypertension in SHR-S by increasing noradrenergic input to the anterior hypothalamus. High-NaCl-fed SHR-S had impaired diuretic and natriuretic responses to an isotonic volume load; Ca2+ enhanced the ability of these animals to adjust fluid volume rapidly via diuresis and natriuresis. This alteration in renal function may contribute to the hypotensive effect of a high Ca2+ diet in NaCl-sensitive hypertension.

Animals↗

Altered stores of atrial natriuretic peptide in specific brain nuclei of NaCl-sensitive spontaneously hypertensive rats.

Previous studies from our laboratories have demonstrated a selective increase in stores of atrial natriuretic peptide (ANP) in the anterior hypothalamus of NaCl-sensitive spontaneously hypertensive rats (SHR-S) compared to NaCl-resistant Wistar-Kyoto (WKY) controls and have suggested that anterior hypothalamic ANP contributes to the pathogenesis of NaCl-sensitive hypertension in SHR-S by local inhibition of norepinephrine release. We have also observed blunting of cardiopulmonary and arterial baroreflex function in SHR-S compared to WKY. In the current study, ANP stores in 12 brain nuclei thought to participate in the pathogenesis of hypertension, including locus coeruleus (LC), A1/C1 area (A1/C1), nucleus tractus solitarii (NTS), medial preoptic nucleus (MPON), suprachiasmatic nucleus (SCN), supraoptic nucleus (SON), anterior hypothalamic area (AHA), paraventricular hypothalamic nucleus (PVN), ventromedial hypothalamic nucleus (VMN), dorsomedial hypothalamic nucleus (DMN), lateral hypothalamic nucleus (LN), and posterior hypothalamic area (PHA), were compared in 10-week-old male SHR-S and WKY rats following 3 weeks of 1% v 8% NaCl feeding. Individual brain nuclei were obtained by the micropunch technique and ANP content of bilateral brain nuclei from individual rats was measured by radioimmunoassay. ANP content was significantly decreased in NTS and LC and elevated in AHA of SHR-S compared to WKY rats on either diet. Dietary NaCl supplementation was associated with increased ANP content in PVN of both strains. These alterations in ANP content in SHR-S may be related to the reduced release of norepinephrine from nerve terminals in AHA and to the presumed central defect in baroreceptor function.

Analysis of Variance↗

Antihypertensive effect of cicletanine is exaggerated in NaCl-sensitive hypertension.

Cicletanine (CIC), a furopyridine derivative, lowers blood pressure in hypertensive animals and humans. We have previously identified an NaCl-sensitive substrain of spontaneously hypertensive rat (SHR-S) that displays enhanced sensitivity to the depressor effects of exogenous atrial natriuretic peptide (ANP) when fed a high NaCl diet. The current study tested the hypotheses that CIC has an exaggerated antihypertensive effect in NaCl-supplemented SHR-S and that this effect might be ANP dependent. CIC (40 mg/kg/day) or vehicle was administered by gavage in a single daily dose for three weeks beginning immediately prior to initiation of 1% or 8% NaCl diets in seven-week-old male SHR-S. CIC significantly decreased mean arterial pressure (MAP) and the ratio of left ventricular and septum weight to body weight (LV + S/BW) in both 8% NaCl- and 1% NaCl-fed SHR-S. The depressor effect of CIC was greater in the 8% NaCl group (-26 mmHg) than in the 1% NaCl group (-13 mmHg). CIC was associated with significant reduction in RAP in the 8% NaCl group but not in the 1% NaCl group. Neither CIC treatment nor 8% NaCl significantly altered plasma ANP or cyclic guanosine monophosphate (GMP) levels in plasma, aorta, or kidney. CIC was associated with significant decreases in plasma norepinephrine (NE) levels in the 1% NaCl group but not in the 8% NaCl group. The data demonstrate that the antihypertensive effect of CIC is exaggerated in NaCl-sensitive hypertension. The antihypertensive effect of CIC appears not to be related to ANP or cyclic GMP but may be related to a combination of a sympatholytic and natriuretic/diuretic effects in SHR-S.

Animals↗

A comparison of the immunomodulating properties of two forms of monophosphoryl lipid A analogues.

This investigation compared the immunomodulating activities of two forms monophosphoryl lipid A, which are analogues of bacterial lipopolysaccharides with little or no toxicity. Tested were a synthetic compound designated 504 and a purified compound, isolated from bacterial cell walls designated MPL. Both of these clinical adjuvant candidates were effective in mice in exerting strong immunomodulating activity in the following areas: (a) enhancing antibody production in young and aging mice; (b) suppressing antibody formation under different experimental conditions; (c) activating macrophages to secrete interleukin 1, hydrogen peroxide, and superoxide anion; and (d) stimulating proliferation of spleen cells from C3H/HeN mice. Both exhibited considerably reduced toxicity in LD50 assays when compared to native lipopolysaccharides (LPS). The LD50 for MPL was 225 times and that of compound 504, 40 times that of native LPS in the exquisitely sensitive, galactosamine-loaded C57BL/6 murine strain.

Adjuvants, Immunologic↗

Self-splicing of the Chlamydomonas chloroplast psbA introns.

We used alpha-32P-GTP labeling of total RNA preparations to identify self-splicing group I introns in Chlamydomonas. Several RNAs become labeled with alpha-32P-GTP, a subset of which is not seen with RNA from a mutant that lacks both copies of the psbA gene. Hybridization of the GTP-labeled RNAs to chloroplast DNA indicates that they originate from the psbA and rrn 23S genes, respectively, the only genes known to contain group I introns in this organism. Introns 1, 2, and 3 of psbA (with flanking exon sequences) were subcloned and transcribed in vitro. The synthetic RNAs were found to self-splice; splicing required Mg2+, GTP, and elevated temperature. In addition, the accuracy of self-splicing was confirmed for introns 1 and 2, and intermediates in the splicing reactions were detected. These results, together with our recent data on the 23S intron, indicate that the ability to self-splice is a general feature of Chlamydomonas group I introns. These findings have significant implications for the mechanism of group I intron splicing and evolution in Chlamydomonas and other chloroplast genomes.

Animals↗

Atrial natriuretic peptide in acute hypoxia-induced pulmonary hypertension in rats.

To test the hypothesis that exogenous atrial natriuretic peptide (ANP) prevents the acute pulmonary pressor response to hypoxia, ANP (20-micrograms/kg bolus followed by 1-microgram.kg-1.min-1 infusion) or vehicle was administered intravenously to conscious rats beginning 3 min before exposure to hypoxia or room air for 90 min. Exogenous ANP abolished the acute pulmonary pressor response to hypoxia in association with marked and parallel increases in plasma ANP and guanosine 5'-cyclic monophosphate (cGMP) and with a significant increase in lung cGMP content. To examine whether endogenous ANP modulates the acute pulmonary pressor response to hypoxia, rats were pretreated with a monoclonal antibody (Ab) to ANP and exposed to hypoxia. Mean pulmonary arterial pressure (MPAP) in the Ab-treated rats was not different from control over the first 6 h of hypoxic exposure. Thereafter, the Ab-treated group had significantly higher MPAP than control. Our data suggest that 1) exogenous ANP blocks the pulmonary pressor response to acute hypoxia via stimulation of cGMP accumulation in the pulmonary vasculature, and 2) endogenous ANP may modulate the subacute, but not acute, phase of hypoxic pulmonary hypertension.

Acute Disease↗

Intrahypothalamic clonidine infusion prevents NaCl-sensitive hypertension.

We have previously shown that dietary NaCl supplementation increases blood pressure and sympathetic nervous system activity in association with decreased norepinephrine release and increased alpha 2-adrenergic receptor number in the anterior hypothalamic area of salt-sensitive spontaneously hypertensive rats (SHR-S) but not in salt-resistant spontaneously hypertensive rats (SHR-R) or Wistar-Kyoto (WKY) rats. Further, acute microinjection of clonidine into the anterior hypothalamic area produced depressor responses that were augmented by high salt feeding in SHR-S but not in SHR-R or WKY rats. The current study tested the hypothesis that chronic infusion of clonidine into the anterior hypothalamic area prevents salt-sensitive hypertension in SHR-S. Beginning at age 7 weeks, immediately before initiation of 1% or 8% salt diets, clonidine (2 ng/min) or saline vehicle was infused into the anterior hypothalamic area or femoral vein of male SHR-S via osmotic minipump for 20 days. In SHR-S fed an 8% salt diet, chronic microinfusion of clonidine into the anterior hypothalamic area offset the hypertensive effect of the dietary salt supplementation and reduced the enhancing effects of dietary salt on left ventricular weight and plasma norepinephrine levels. In contrast, chronic microinfusion of clonidine into the anterior hypothalamic area did not significantly affect any of these measures in 1% salt-fed SHR-S. Intravenous infusion of clonidine at the rate used for the anterior hypothalamic area infusion did not alter any of these measures in 8% salt-fed SHR-S.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Atrial natriuretic peptide inhibits sympathetic outflow in NaCl-sensitive spontaneously hypertensive rats.

The current study tested the hypothesis that circulating atrial natriuretic peptide (ANP) inhibits sympathetic outflow, as reflected in lumbar sympathetic nerve activity (LSNA), in NaCl-sensitive spontaneously hypertensive rats (SHR-S) and that this effect is exaggerated by high NaCl feeding. NaCl-resistant SHR (SHR-R) and Wistar-Kyoto (WKY) rats maintained on basal and high-NaCl diets were used as controls. Intravenous administration of ANP to conscious, freely moving rats with intact baroreflexes decreased blood pressure and LSNA in SHR-S, SHR-R and WKY rats maintained on basal or high-NaCl diets for 2-3 weeks. The depressor response to intravenous ANP was greater in 8% NaCl-fed SHR-S than in any other group; the LSNA response was greater in SHR-S on either diet than in any other group. Intracerebroventricular administration of ANP evoked small, transient sympatholytic responses in SHR-S on both diets and minimal responses in SHR-R and WKY rats; these responses could not be attributed to leakage of ANP into the peripheral circulation. Thus, circulating ANP has a sympatholytic effect in SHR-S that is not amplified by high-NaCl feeding and can be only partially accounted for by a central action.

Animals↗

Effects of gastrointestinal peptides on formation of gallstone in guinea pigs.

In light of the effects of gastrointestinal (GI) peptides on bile secretion and biliary tract mobility, we studied the effects of GI peptides on gallstone formation in guinea pigs fed on low protein lithogenic diet. The peptides under study included cholecystokinin octapeptide (CCK-8), vasoactive intestinal peptide (VIP), somatostatin (SRIF), secretin (SEC), and neurotensin (NT). Hepatic bile flow, electrolytes, and other bile components were also measured. It was found that CCK-8 and VIP suppressed the formation of gallstones and increased hepatic bile flow and Na+, K+, Cl- output significantly. On the other hand, SRIF significantly promoted gallstone formation. The rates of gallstone formation in CCK-8, VIP, and SRIF treated guinea pigs were 15.4%, 23.5%, and 88.0%, respectively, in contrast to 56.8% in the control group. The inhibitory effect of CCK-8 and promoting effect of SRIF on gallstone formation were dose-dependent.

Animals↗

Inconsistent effectiveness of myocardial preservation among cardiac chambers during hypothermic cardioplegia.

The purpose of this study was to examine the selective and differential natures of ischemic injuries among three cardiac chambers (right atrium, right ventricle, and left ventricle) from the viewpoint of ultrastructural morphometric study. Twenty consecutive adult patients undergoing cardiac operations were studied. The duration of aortic crossclamp time varied from 36 to 142 minutes (mean 83.4 +/- 36.4 minutes). Two serial specimens (preischemic and ischemic) were obtained from the right atrium, the right ventricle, and the left ventricle, respectively. A total of 120 biopsy specimens was obtained from these 20 patients. The average mitochondrial surface area of the left ventricle was 0.308 +/- 0.062 micron 2 in the preischemic stage and 0.352 +/- 0.083 microns 2 in the ischemic stage. This represented a 14.3% increase in mitochondrial surface area after ischemic injury (p less than 0.01). The mitochondrial surface area of the right ventricle showed an average increase of 43.7%, from 0.252 +/- 0.036 micron 2 in the preischemic stage to 0.362 +/- 0.087 micron 2 in the ischemic stage (p less than 0.0005). With respect to the mitochondrial surface area of the right atrium, there was an increase of 88.0%, from 0.217 +/- 0.044 micron 2 in the preischemic stage to 0.408 +/- 0.084 micron 2 (p less than 0.0005). The difference of mitochondrial swelling among three chambers was statistically significant (right atrium versus right ventricle versus left ventricle, p less than 0.0005). Moreover, the differences of mitochondrial swelling between any two chambers were also highly significant (right atrium versus right ventricle, p less than 0.0005; right ventricle versus left ventricle, p less than 0.01; right atrium versus left ventricle, p less than 0.0005). In conclusion, our findings suggest that from the viewpoint of ultrastructural morphometric study myocardial injury after an average of 83 minutes of ischemic arrest is poorer in the right chambers of the heart than in the left ventricle, with the right atrium having the poorest preservation.

Adult↗

The effect of race on waiting time in two urban emergency departments.

This study examines the relation between patient race and waiting time in two urban Emergency Departments, located in the northeastern United States. Consecutive patients presenting with lacerations make up the subjects in the study. In order to control for the effect of disease severity, we restricted the sample to patients presenting with small, single lacerations requiring sutures. Patients who were intoxicated, had experienced syncope, had been involved in motor vehicle accidents, or who required tests or consultation were excluded. Taking socio-demographic (age, sex, insurance status) and clinical variables (location of laceration, time of day, day of week) into account, we found no substantial difference in total time spent in the Emergency Departments between whites and non-whites.

Attitude of Health Personnel↗

RNA splicing in Chlamydomonas chloroplasts. Self-splicing of 23 S preRNA.

The 23 S rRNA gene of the Chlamydomonas reinhardtii chloroplast contains an 888-base pair intron with structural features characteristic of Group I introns. The nuclear, chloroplast ribosome-deficient mutant of C. reinhardtii, ac20, overaccumulates a approximately 3.6-kilobase unspliced 23 S preRNA compared to wild-type cells. We have used [alpha-32P]GTP labeling of total RNA preparations from ac20 to rapidly determine that 23 S preRNA is capable of self-splicing. The ability of the 23 S intron (with flanking exon sequences) to correctly catalyze its own splicing was confirmed using RNA produced by in vitro transcription of cloned DNA. These results identify the first example of a self-splicing RNA of chloroplast origin.

Base Sequence↗