Biomedical subjects

J Y Li

Publications and source records attributed to J Y Li.

At least 19 recordsLinked to original sources

PubMed2001

Agouti-related protein is a mediator of diabetic hyperphagia.

To explore the role of agouti-related protein (AGRP) in diabetic hyperphagia changes in hypothalamic AGRP mRNA levels were examined in diabetic rats. Rats rendered diabetic by streptozotocin displayed marked hyperglycemia (blood glucose 456.0+/-8.4 mg/dl versus 71.8+/-1.9 mg/dl) and hyperphagia (36.9+/-1.0 g/day versus 22.0+/-0.4 g/day), that was associated with a 286.6+/-4.4% increase in hypothalamic AGRP mRNA and a 178.9+/-13.5% increase in hypothalamic NPY mRNA. Insulin treatment of diabetic rats partially corrected blood glucose (147.4+/-13.1 mg/dl) and ameliorated hyperphagia (26.6+/-2.0 g/day). Insulin replacement was also associated with a return of hypothalamic AGRP mRNA (111.7+/-8.3% of controls) and NPY mRNA (125.0+/-8.9% of controls) from the elevated levels that were observed in untreated diabetic rats. In contrast to insulin treated rats, sodium orthovanadate treated diabetic rats remained significantly hyperglycemic (361.5+/-12.5 mg/dl). However, despite their persistent hyperglycemia, orthovanadate treated diabetic rats were still observed to have a significant reduction of hypothalamic AGRP mRNA (138.7+/-11.4%) and NPY mRNA (129.9+/-9.8%). Simultaneous measurement of serum leptin revealed suppressed levels in both untreated diabetic (0.5+/-0.1 ng/ml) and sodium orthovanadate treated rats (0.5+/-0.1 ng/ml) compared to non-diabetic controls (2.1+/-0.1 ng/ml). These data indicate that AGRP is a mediator of diabetic hyperhpagia and suggest that insulin can directly influence hypothalamic AGRP and NPY mRNA expression.

Agouti-Related Protein↗

PubMed2001

Carbachol induces homologous steroidogenic refractoriness of bovine fasciculata-reticularis cells.

Recently it was shown that the cholinergic agonist carbachol stimulates cortisol production in bovine ZFR cells via muscarinic receptor M(3). In the present study, we investigated the effect of chronic cholinergic stimulation on steroidogenic response and muscarinic receptor regulation in ZFR cells. Cortisol secretion of ZFR cells treated with 10(-4) M of carbachol decreased in a dose- and time-dependent manner. The carbachol-elicited loss of response was associated with a decrease in M(3) receptor number, which was also time- and dose-dependent. The down-regulation of the receptors was not associated with the decrease of M(3) receptor mRNA level. The marked steroidogenic desensitization caused by pretreatment of carbachol did not alter ACTH or angiotensin II activated steroid response. Northern blot analysis showed that carbachol pretreatment did not change the gene expression of P450scc, P450cl7, 3betaHSD and StAR mRNAs. These results suggest that carbachol induces homologous steroidogenic refractoriness of ZFR cells.

Adrenocorticotropic Hormone↗

PubMed2001

Blood-brain barrier genomics.

The blood-brain barrier (BBB) is formed by the brain microvascular endothelium, and the unique transport properties of the BBB are derived from tissue-specific gene expression within this cell. The current studies developed a gene microarray approach specific for the BBB by purifying the initial mRNA from isolated rat brain capillaries to generate tester cDNA. A polymerase chain reaction-based subtraction cloning method, suppression subtractive hybridization (SSH), was used, and the BBB cDNA was subtracted with driver cDNA produced from mRNA isolated from rat liver and kidney. Screening 5% of the subtracted tester cDNA resulted in identification of 50 gene products and more than 80% of those were selectively expressed at the BBB; these included novel gene sequences not found in existing databases, ESTs, and known genes that were not known to be selectively expressed at the BBB. Genes in the latter category include tissue plasminogen activator, insulin-like growth factor-2, PC-3 gene product, myelin basic protein, regulator of G protein signaling 5, utrophin, IkappaB, connexin-45, the class I major histocompatibility complex, the rat homologue of the transcription factors hbrm or EZH1, and organic anion transporting polypeptide type 2. Knowledge of tissue-specific gene expression at the BBB could lead to new targets for brain drug delivery and could elucidate mechanisms of brain pathology at the microvascular level.

Animals↗

PubMed2000

Molecular determinants of ligand binding to the human melanocortin-4 receptor.

To elucidate the molecular basis for the interaction of ligands with the human melanocortin-4 receptor (hMC4R), agonist structure-activity studies and receptor point mutagenesis were performed. Structure-activity studies of [Nle(4), D-Phe(7)]-alpha-melanocyte stimulating hormone (NDP-MSH) identified D-Phe7-Arg8-Trp9 as the minimal NDP-MSH fragment that possesses full agonist efficacy at the hMC4R. In an effort to identify receptor residues that might interact with amino acids in this tripeptide sequence 24 hMC4R transmembrane (TM) residues were mutated (the rationale for choosing specific receptor residues for mutation is outlined in the Results section). Mutation of TM3 residues D122 and D126 and TM6 residues F261 and H264 decreased the binding affinity of NDP-MSH 5-fold or greater, thereby identifying these receptor residues as sites potentially involved in the sought after ligand-receptor interactions. By examination of the binding affinities and potencies of substituted NDP-MSH peptides at receptor mutants, evidence was found that core melanocortin peptide residue Arg8 interacts at a molecular level with hMC4R TM3 residue D122. TM3 mutations were also observed to decrease the binding of hMC4R antagonists. Notably, mutation of TM3 residue D126 to alanine decreased the binding affinity of AGRP (87-132), a C-terminal derivative of the endogenous melanocortin antagonist, 8-fold, and simultaneous mutations D122A/D126A completely abolished AGRP (87-132) binding. In addition, mutation of TM3 residue D122 or D126 decreased the binding affinity of hMC4R antagonist SHU 9119. These results provide further insight into the molecular determinants of hMC4R ligand binding.

Agouti-Related Protein↗

PubMed2000

Gastric dysplasia and gastric cancer: Helicobacter pylori, serum vitamin C, and other risk factors.

BACKGROUND: Gastric cancer is generally thought to arise through a series of gastric mucosal changes, but the determinants of the precancerous lesions are not well understood. To identify such determinants, we launched a follow-up study in 1989-1990 among 3433 adults in Linqu County, China, a region with very high rates of gastric cancer. METHODS: Data on cigarette smoking, alcohol consumption, and other characteristics of the participants were obtained by interview in 1989-1990, when an initial endoscopy was taken. At study entry, antibodies to Helicobacter pylori were assayed in 2646 adults (77% of people screened), and levels of serum micronutrients were measured in approximately 450 adults. Follow-up endoscopic and histopathologic examinations were conducted in 1994. Antibodies to H. pylori, levels of serum micronutrients, and other baseline characteristics were compared between subjects whose condition showed progression to dysplasia or gastric cancer from study entry to 1994 and subjects with no change or with regression of their lesions over the same time frame. All P: values are two-sided. RESULTS: The presence of H. pylori at baseline was associated with an increased risk of progression to dysplasia or gastric cancer (odds ratio [OR] = 1.8; 95% confidence interval [CI] = 1.2-2.6). The risk of progression to dysplasia or gastric cancer also was moderately increased with the number of years of cigarette smoking. In contrast, the risk of progression was decreased by 80% (OR = 0.2; 95% CI = 0.1-0.7) among subjects with baseline ascorbic acid levels in the highest tertile compared with those in the lowest tertile, and there was a slightly elevated risk in those individuals with higher levels of alpha-tocopherol. CONCLUSIONS: H. pylori infection, cigarette smoking, and low levels of dietary vitamin C may contribute to the progression of precancerous lesions to gastric cancer in this high-risk population.

Adult↗

PubMed2000

Postanoxic parkinsonism: clinical, radiologic, and pathologic correlation.

The authors report a 72-year-old patient who presented with parkinsonism after hypoxic-ischemic insult. T1-weighted MRI revealed high signal intensity lesions in the basal ganglia. Pathologic study of the brain disclosed multiple foci of old infarcts with gliosis and lipid-laden and hemosiderin-laden macrophages, indicating a previous minor hemorrhage after infarction. This observation provided pathologic correlation with the patient's clinical symptoms and MRI.

Aged↗

PubMed2000

Cytoplasmic dynein conversion at a crush injury in rat peripheral axons.

Cytoplasmic dynein is a motor for retrograde axonal transport for movement of membranous organelles toward the neuronal cell body. However, cytoplasmic dynein is synthesized in the cell body and conveyed along the axon to nerve terminals. To characterize the axonal transport of cytoplasmic dynein in relation to synaptic vesicles and other membrane compartments, immunocytochemical and cytofluorimetric scanning analyses of crush-operated rat sciatic nerves were performed. Distal to the crush, the kinetics of dynein accumulation were consistent with its role in the retrograde transport of membranous organelles. During the initial 3 hr after crush, only small amounts of dynein-immunoreactive material accumulated proximal to the crush. This is consistent with metabolic labeling studies showing that most of the dynein moving in the anterograde direction is in the slow component of axonal transport. Thereafter, the rate of proximal accumulation of dynein increased, and by 8 hr postcrush a large amount of dynein immunoreactivity was observed. This accelerated accumulation may be due to recruitment of dynein from slow component b onto organelles proximal to the crush. Double labeling demonstrated that dynein immunoreactivity colocalized with synaptophysin, a transmembrane protein found in small, clear synaptic vesicles. In contrast, dynein immunoreactivity did not colocalize well with calcitonin gene-related peptide (CGRP), a peptide matrix marker for some large dense-cored vesicles. Finally, dynein immunoreactivity colocalized with the anterograde transport motor kinesin both proximal and distal to a crush, suggesting that kinesin may carry some dynein-containing membrane compartments during fast anterograde axonal transport.

Animals↗

PubMed2000

Cryptocin, a potent tetramic acid antimycotic from the endophytic fungus Cryptosporiopsis cf. quercina.

[formula: see text] The endophytic fungus Cryptosporiopsis cf. quercina produces cryptocin in culture. Among other fungi, this unique tetramic acid displays antimycotic activity against Pyricularia oryzae, the causal agent of rice blast disease. Cryptocin also possesses activity against a wide variety of plant pathogenic but not human pathogenic fungi. The fine rhomboid-like crystals of cryptocin allowed structural elucidation by X-ray crystallography. The importance of cryptocin to the symbiotic relationship of C. quercina to its hosts is briefly discussed.

Ascomycota↗

PubMed2000

Increased cerebral blood flow in MELAS shown by Tc-99m HMPAO brain SPECT.

We report cerebral SPECT studies on two siblings with the syndrome of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). Tc-99m HMPAO brain SPECT was performed 8, 19 and 30 days after a stroke-like episode in one case and 10 days after a stroke-like episode, 6 h after a partial seizure and as a follow-up study in the other. Increased blood flow was seen in both these patients with stroke-like episodes due to MELAS. The cause of the increased blood flow is uncertain, but it may be related to the decreased pH created by local increase in lactic acid.

Adult↗

PubMed2000

The cardiovascular effects of PFRFamide and PFR(Tic)amide, a possible agonist and antagonist of neuropeptide FF (NPFF).

Neuropeptide FF (NPFF), an endogenous opioid-related neuromodulater, has been reported to show significant effects on the cardiovascular system, namely elevation of arterial blood pressure (BP) and heart rate (HR) in rats. In the present study, we synthesized two novel NPFF analogs, PFRFamide (putative NPFF agonist) and PFR(Tic)amide (putative NPFF antagonist), and examined their cardiovascular effect on BP and HR in anesthetized rats. The arterial mean BP and HR were measured by way of direct femoral artery catheterization. The data showed that PFRFamide increased BP in a dose-dependent manner, while PFR(Tic)amide decreased BP dose-dependently. These results revealed the possibility of PFRFamide and PFR(Tic)amide to be NPFF agonist and antagonist (or inverse agonist), respectively. These two NPFF analogs may possess potential in new drug design, and the NPFF system could be very important in mammalian cardiovascular function.

Amides↗

PubMed2000

Effect of extrusion on isoflavone content and antiproliferative bioactivity of soy/corn mixtures.

The present studies were conducted to determine changes in the quantities of select isoflavones and in the bioactivity (ability to inhibit proliferation of human breast cancer cell lines) of extracts from blends of soy protein and cornmeal during extrusion processing. The extrusion of samples resulted in an average 24% decrease in the concentration of total isoflavones for all samples. Although the amounts of specific genistein-derived and daidzein-derived forms changed following extrusion, the content of the aglycones genistein and daidzein per g sample generally did not change. The extrusion of samples generally resulted in decreased antiproliferative action toward breast cancer cells, although antiproliferative activity was not eliminated. Therefore, extrusion of soy protein/cornmeal-containing foods are likely to retain a considerable portion of their isoflavone content and some of the health benefits associated with soy.

Cell Division↗

PubMed2000

Biliary tract reconstruction using an autologous vein graft in rats.

Numerous biologic and synthetic materials have been used with limited success as an interposed graft to repair segmental common bile duct (CBD) defects. The authors report here that an autologous vein graft can be successfully used to correct a CBD deficit contingent on accurate microsurgical technique immediate stenting and rapid graft vascularization. Thirty Sprague-Dawley rats underwent laparotomy and the experimental group (n=25) had a 3-mm segment of the CBD excised. The CBD defect was repaired using an interposed femoral vein graft aided by a plastic stent. The control group (n=5) had the CBD cut and repaired by means of primary anastomosis. The experimental group was subdivided into three sub-groups each examined at three different postoperative intervals: 1, 4 and 12 weeks. The results showed that inflammation was apparent in the venous wall following the first postoperative week. A progressive loss of the vascular endothelium and replacement with the columnar epithelium typical of the CBD was seen in the vein graft. Nineteen of the 25 experimental rats (76 percent) of the animals survived without complication from the surgery and there were no abnormalities in the liver biochemical tests of these animals. Any biliary tract obstruction that developed was attributed to dislocation of the stent leading to collapse of the vein graft (experimental group), or constriction of the anastomosis (control group). This study demonstrates that biliary tract reconstruction using an autologous vein graft can be successfully performed in a rat model of CBD repair. The application of this method to the clinical setting is also discussed.

Animals↗

PubMed2000

Selective Lutheran glycoprotein gene expression at the blood-brain barrier in normal brain and in human brain tumors.

The Lutheran (LU) glycoprotein was shown to be a specific marker of brain capillary endothelium, which forms the blood-brain barrier (BBB) in vivo. A 1.5 kb partial cDNA encoding the bovine LU was isolated from a bovine brain capillary cDNA library. Sequence analysis showed that the bovine and human LU had a 75% and 79% identity in the amino acid and nucleotide sequences, respectively. Northern blot analysis demonstrated a very high level of gene expression of the LU transcript in freshly isolated bovine brain capillaries, but no measurable LU mRNA in whole bovine brain. The high level of LU gene expression was maintained when bovine brain capillary endothelium was grown in tissue culture. Because many BBB specific genes are downregulated in tissue culture and in brain tumors, the expression of the LU mRNA and immunoactive LU protein was investigated in primary and metastatic human brain tumors. Immunocytochemistry of fresh frozen human brain and human brain tumors showed abundant immunostaining of brain capillary endothelium. Northern blot analysis showed the presence of LU transcripts in a panel of primary and metastatic human brain tumors. These studies demonstrated that the LU glycoprotein was a novel new marker of the BBB, and unlike other BBB specific genes, there was a persistent gene expression of the LU glycoprotein both in brain capillary endothelial cells grown in culture and in the endothelium of capillaries perfusing human brain cancer.

Amino Acid Sequence↗

PubMed2000

Molecular detection of Mycobacterium tuberculosis in tissues showing granulomatous inflammation without demonstrable acid-fast bacilli.

Early diagnosis of tuberculosis (TB) is important for early medical intervention and prevention of spread of the bacteria. It is not uncommon to observe granulomatous inflammation but without demonstrable acid-fast bacilli (AFB) on Ziehl-Neelsen (ZN) staining in tissues sent for histologic examination, and the definitive diagnosis of TB cannot be made because no concurrent tissue is sent for TB culture. In this study, the authors explored the feasibility of using polymerase chain reaction (PCR) for early detection of Mycobacterium tuberculosis (Mtb) in formalin-fixed, paraffin-embedded tissues where a definite diagnosis of TB cannot be made. One hundred fifteen patients (131 paraffin blocks of biopsy specimens) with granulomatous inflammation but ZN-negative for AFB were studied. DNA was extracted from paraffin sections and amplified by PCR with the IS6110 primers (specific for the Mtb complex) and the specific 122-base pairs (bp) PCR product was detected by agarose gel electrophoresis. Sixty-eight of the 115 (59%) patients were TB-PCR positive, thus enabling definite diagnosis of TB in significant numbers of these patients in 3 days. The authors conclude that molecular diagnosis by PCR is useful for early detection of TB in histologic material where morphologic features are suggestive but not confirmatory because of negative staining for AFB.

Adolescent↗

PubMed2000

Regulation by adrenocorticotropin (ACTH), angiotensin II, transforming growth factor-beta, and insulin-like growth factor I of bovine adrenal cell steroidogenic capacity and expression of ACTH receptor, steroidogenic acute regulatory protein, cytochrome P450c17, and 3beta-hydroxysteroid dehydrogenase.

The purpose of this study was to evaluate the time-course effect of a 36-h treatment with ACTH (10(-8) M), transforming growth factor-beta1 (TGFbeta1; 10(-10) M), angiotensin II (AngII; 10 (-7) M), and insulin-like growth factor I (IGF-I; 10(-8) M) on the steroidogenic capacity of bovine adrenocortical cells (BAC) and on messenger RNA (mRNA) levels of ACTH receptor, cytochrome P450c17, 3beta-hydroxysteroid dehydrogenase (3betaHSD), steroidogenic acute regulatory protein (StAR), and StAR protein. ACTH and IGF-I enhanced, in a time-dependent manner, the acute 2-h ACTH-induced cortisol production, whereas TGFbeta 1 and AngII markedly reduced it. ACTH, IGF-I, and AngII increased ACTH receptor mRNA, but the opposite was observed after TGFbeta1 treatment. ACTH and IGF-I increased P450c17 and 3betaHSD mRNAs, whereas AngII and TGFbeta1 had the opposite effects. However, the effects of the four peptides on ACTH-induced cortisol production appeared before any significant alterations of the mRNA levels occurred. The most marked and rapid effect of the four peptides was on StAR mRNA. The stimulatory effect of ACTH was seen within 1.5 h, peaked at 4-6 h, and declined thereafter, but at the end of the 36-h pretreatment, the levels of StAR mRNA and protein were higher than those in control cells. IGF-I also enhanced StAR mRNA levels within 1.5 h, and these levels remained fairly constant. The effects of AngII on StAR mRNA expression were biphasic, with a peak within 1.5-3 h, followed by a rapid decline to almost undetectable levels of both mRNA and protein. TGFbeta1 had no significant effect during the first 3 h, but thereafter StAR mRNA declined, and at the end of the experiment the StAR mRNA and protein were almost undetectable. Similar results were observed when cells were treated with ACTH plus TGFbeta1. A 2-h acute ACTH stimulation at the end of the 36-h pretreatment caused a higher increase in StAR mRNA and protein in ACTH- or IGF-I-pretreated cells than in control cells, which, in turn, had higher levels than cells pretreated with TGFbeta1, ACTH plus TGFbeta1, or AngII. These results and the fact that the stimulatory (IGF-I) or inhibitory (AngII and TGFbeta1) effects on ACTH-induced cortisol production were more pronounced than those on the ability of cells to transform pregnenolone into cortisol strongly suggest that regulation of StAR expression is one of the main factors, but not the only one, involved in the positive (IGF-I) or negative (TGFbeta1 and AngII) regulation of BAC for ACTH steroidogenic responsiveness. A high correlation between steady state mRNA level and acute ACTH-induced cortisol production favors this conclusion.

3-Hydroxysteroid Dehydrogenases↗

PubMed2000

Agouti-related protein-like immunoreactivity: characterization of release from hypothalamic tissue and presence in serum.

A novel RIA was used to examine the release of agouti-related protein-like immunoreactivity (AGRP-LI) from perfused rat hypothalamic tissue slices and to characterize AGRP-LI in rat serum. A continuous low level basal AGRP-LI release was observed from hypothalami of rats fed ad libitum before the rats were killed. Basal AGRP-LI release was 3-fold greater in rats fasted 48 h. In fasted animals leptin dose-dependently suppressed basal AGRP-LI release. In fed animals no change in basal AGRP-LI release was detected in response to 10(-6) M alpha-MSH, orexin B, melanin-concentrating hormone, or serotonin. HPLC analysis of AGRP-LI in rat serum identified a single peak that eluted in close proximity to synthetic AGRP (87-132) and mouse [Leu127Pro]AGRP and that was identical to the peak seen in hypothalamic and adrenal tissue extracts. The serum concentration of AGRP-LI in rats fed ad libitum was 0.865+/-0.323 nmol/liter (mean +/- SE). Food deprivation resulted in a slow, but statistically significant rise in serum immunoreactivity at 48 h [1.174+/-0.118 nmol/liter (mean +/- SE)]. Bilateral adrenalectomy did not change serum levels of AGRP-LI. These studies demonstrate that in the rat there are different levels of basal hypothalamic AGRP-LI release in fed and fasted states and that in the fasted rat this release can be profoundly suppressed by leptin. These studies also suggest that AGRP is present in the systemic circulation of rats.

Adrenal Glands↗

PubMed2000

Increased tyrosine hydroxylase immunoreactivity in bladder tissue from patients with classic and nonulcer interstitial cystitis.

PURPOSE: Interstitial cystitis is a chronic debilitating condition which mainly affects women. Accumulated evidence indicates that interstitial cystitis is a heterogeneous syndrome. The nonulcer subtype appears different than classic interstitial cystitis in regard to symptoms, and endoscopic and histological findings as well as response to various treatments. We further explore the neurogenic nature of this disease using indirect immunofluorescence to evaluate the presence and density of various autonomic and sensory nerve fibers. MATERIALS AND METHODS: Specimens from the bladder wall of 6 patients with classic interstitial cystitis, 7 with nonulcer interstitial cystitis and 6 controls were evaluated to determine the presence and density of nerve fibers containing tyrosine hydroxylase, calcitonin gene-related peptide, neuropeptide Y and substance P using specific antibodies, and the general presence of nerve fibers using a mixture of antibodies against nerve filament, neuron specific enolase and S-100 protein. RESULTS: Increased density and number of nerve fibers immunoreactive for tyrosine hydroxylase were noted in interstitial cystitis cases compared to controls. Furthermore, there was a difference between classic and nonulcer disease in the overall density of nerves using the antibody mixture. CONCLUSIONS: Our findings indicate an altered peripheral sympathetic innervation in interstitial cystitis cases, which may be an indication of primary neurogenic etiology. The difference in nerve density observed after incubation with the antibody mixture between classic and nonulcer interstitial cystitis supports the hypothesis that the 2 forms represent separate entities.

Adult↗

PubMed2000

[Genetical effect of different rye chromosomes on the acid phosphatase (Acph) secretion of common wheat roots under phosphorus starvation conditions].

The effects of different rye chromosomes on Acph secretion of common wheat roots under P starvation conditions were studied by using a set of Chinese Spring-Imperial (CS-IMP) alien addition lines as materials. The Acph activity measurement results showed that P starvation is an induction factor for Acph gene expression; Different chromosomes of Imperial rye in Chinese Spring background has different effects on the secretion of Acph by corresponding addition line roots. Among them, chromosome 1R had the strongest promoting effect; The IEF diagram of Acph isozymes clearly demonstrated that chromosome 1R in rye genome carries P starvation inducible Acph gene(s).

Acid Phosphatase↗