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Biomedical subjects

L Zhou

Publications and source records attributed to L Zhou.

At least 379 records · Page 21Linked to original sources
PubMed1997

Synthetic strategies for the preparation of precursor polymers and of microcapsules suitable for cellular entrapment by polyelectrolyte complexation of those polymers.

The production of microcapsules suitable for the entrapment of mammalian cell by means of polyelectrolyte complexation has, of a necessity, led to the development of novel strategies for the preparation of relatively bioinert polymers which complex efficiently under unique conditions to produce a mechanically resilient membrane with efficient transport properties. In this communication we relate a brief overview of capsule-membrane forming systems for the immunoisolation (or potential immunoisolation) of mammalian cells, which are based upon the complexation of polyelectrolyte (PE) polymers; with emphasis on precursor synthesis and relationships between precursor polymer structure and capsule membrane stability.

Animals↗
PubMed1997

Tissue uptake and interconversion of plasma unesterified 14C linoleic acid in the guinea pig.

Part of the arachidonic acid (20:4, n - 6) pools in the gastrointestinal tract and blood forming tissues may be formed by local interconversion of linoleic acid (18:2, n - 6) taken up as a free fatty acid from blood. This study examined the rate of uptake and interconversion of unesterified 14C-18:2 by different tissues in young guinea pigs. The clearance rate of 14C-18:2 was fast, and the initial half-life was 6.3 s. The retention of 14C in tissue lipids was 1.6-1.8% g-1 in the liver, 0.4% g-1 in stomach, 0.7% g-1 in small intestine, 0.2% g-1 in colon, 0.4% g-1 in bone marrow and 0.7% g-1 in spleen. Autoradiographic localization of 3H-18:2 under light microscope demonstrated that most of the 3H radioactivity of the gastrointestinal tract was in the mucosa, in both villus and crypt cells. In bone marrow smears, a high density of silver grains was found in megakaryocytes. The percent of 14C in delta6 desaturase products was higher in gastrointestinal tract, heart, lung, bone marrow and spleen than in liver. The ratio of 14C-20:3/14C-20:4 formation in most tissues was high, and a notable finding being a lower rate of 20:4 formation from plasma free 18:2 in the liver, (170 pmol min-1) than in the gastrointestinal tract (428 pmol min-1) and bone marrow (1203 pmol min-1). The local interconversion of 18:2 into delta6 desaturase products is thus an important source of 20:4 in these organs in guinea pigs.

Animals↗
PubMed1997

The complete genome sequence of the hyperthermophilic, sulphate-reducing archaeon Archaeoglobus fulgidus.

Archaeoglobus fulgidus is the first sulphur-metabolizing organism to have its genome sequence determined. Its genome of 2,178,400 base pairs contains 2,436 open reading frames (ORFs). The information processing systems and the biosynthetic pathways for essential components (nucleotides, amino acids and cofactors) have extensive correlation with their counterparts in the archaeon Methanococcus jannaschii. The genomes of these two Archaea indicate dramatic differences in the way these organisms sense their environment, perform regulatory and transport functions, and gain energy. In contrast to M. jannaschii, A. fulgidus has fewer restriction-modification systems, and none of its genes appears to contain inteins. A quarter (651 ORFs) of the A. fulgidus genome encodes functionally uncharacterized yet conserved proteins, two-thirds of which are shared with M. jannaschii (428 ORFs). Another quarter of the genome encodes new proteins indicating substantial archaeal gene diversity.

Archaeoglobus fulgidus↗
PubMed1997

Insulin receptor substrate-2 (IRS-2) can mediate the action of insulin to stimulate translocation of GLUT4 to the cell surface in rat adipose cells.

Insulin receptor substrates-1 and -2 (IRS-1 and -2) are important substrates of the insulin receptor tyrosine kinase. Previous studies have focused upon the role of IRS-1 in mediating the actions of insulin. In the present study, we demonstrate that IRS-2 can mediate translocation of the insulin responsive glucose transporter GLUT4 in a physiologically relevant target cell for insulin action. Co-immunoprecipitation experiments performed on cell lysates derived from freshly isolated rat adipose cells incubated in the presence or absence of insulin indicated that twice as much phosphatidylinositol 3-kinase was associated with endogenous IRS-1 as with IRS-2 after insulin stimulation. When rat adipose cells in primary culture were transfected with expression vectors for IRS-1 or IRS-2, we observed 40-fold overexpression of human IRS-1 or murine IRS-2. In addition, anti-phosphotyrosine immunoblotting experiments confirmed that the recombinant substrates were phosphorylated in response to insulin stimulation. To examine the role of IRS-2 in insulin-stimulated translocation of GLUT4, we studied the effects of overexpression of IRS-1 and -2 on translocation of a co-transfected epitope-tagged GLUT4 (GLUT4-HA). Overexpression of IRS-1 or IRS-2 in adipose cells resulted in a significant increase in the basal level of cell surface GLUT4 (in the absence of insulin). Interestingly, at maximally effective concentrations of insulin (60 nM), the level of cell surface GLUT4 in cells overexpressing IRS-1 or -2 significantly exceeded the maximal recruitment observed in the control cells (160 and 135% of control, respectively; p < 0.003). Our data directly demonstrate that IRS-2, like IRS-1, is capable of participating in insulin signal transduction pathways leading to the recruitment of GLUT4. Thus, IRS-2 may provide an alternative pathway for critical metabolic actions of insulin.

Adipose Tissue↗
PubMed1997

Proton magnetic resonance spectroscopy of the anterior cingulate region in schizophrenia.

The authors measured N-acetylaspartate (NAA, a putative neuronal marker), choline and creatine in the anterior cingulate region of 26 schizophrenic patients and 16 control subjects using in vivo proton magnetic resonance spectroscopic imaging (1H MRSI). Relative to the control group, the patients with schizophrenia demonstrated significantly lower NAA in both the right and left anterior cingulate regions. There was no association between NAA and duration of illness or medication dosage. No group differences or lateralized asymmetries in choline or creatine were noted. The NAA findings provide support for either neuronal dysfunction or neuronal loss in the anterior cingulate region in schizophrenia. The absence of choline signal elevation does not support accelerated turnover of membrane phospholipids which might be expected if there were ongoing neuronal atrophy or neuronal necrosis.

Adult↗
PubMed1997

Myoclonic epilepsy and ragged red fibers (MERRF) syndrome: selective vulnerability of CNS neurons does not correlate with the level of mitochondrial tRNAlys mutation in individual neuronal isolates.

Selective vulnerability of subpopulations of neurons is a striking feature of neurodegeneration. Mitochondrially transmitted diseases are no exception. In this study CNS tissues from a patient with myoclonus epilepsy and ragged red fibers (MERRF) syndrome, which results from an A to G transition of nucleotide (nt) 8344 in the mitochondrial tRNALys gene, were examined for the proportion of mutant mtDNA. Either individual neuronal somas or the adjacent neuropil and glia were microdissected from cryostat tissue sections of histologically severely affected brain regions, including dentate nuclei, Purkinje cells, and inferior olivary nuclei, and from a presumably less affected neuronal subpopulation, the anterior horn cells of the spinal cord. Mutant and normal mtDNA were quantified after PCR amplification with a mismatched primer and restriction enzyme digestion. Neurons and the surrounding neuropil and glia from all CNS regions that were analyzed exhibited high proportions of mutant mtDNA, ranging from 97.6 +/- 0.7% in Purkinje cells to 80.6 +/- 2.8% in the anterior horn cells. Within each neuronal group that was analyzed, neuronal soma values were similar to those in the surrounding neuropil and glia or in the regional tissue homogenate. Surprisingly, as compared with controls, neuronal loss ranged from 7% of the Purkinje cells to 46% of the neurons of the dentate nucleus in MERRF cerebellum. Thus, factors other than the high proportion of mutant mtDNA, in particular nuclear-controlled neuronal differences among various regions of the CNS, seem to contribute to the mitochondrial dysfunction and ultimate cell death.

Adolescent↗
PubMed1997

Sex steroids and bone mass in older men. Positive associations with serum estrogens and negative associations with androgens.

The purpose of this study was to determine whether bone density in older men was associated with serum sex steroids or sex hormone binding globulin (SHBG). Bone density and sex steroids were measured in men over age 65 at 6-mo intervals for an average of 2.1 yr. Bone density was significantly positively associated with greater serum E2 concentrations (+0.21 < r < +0.35; 0.01 < P < 0.05) at all skeletal sites. There were weak negative correlations between serum testosterone and bone density (-0.20 < r < -0.28; 0.03 < P < 0.10) at the spine and hip. SHBG was negatively associated only with bone density in the greater trochanter (r = -0.26, P < 0.05). Greater body weight was associated with lower serum testosterone and SHBG, and greater E2. Because of these associations, regression models which adjusted for age, body weight, and serum sex steroids were constructed; these accounted for 10-30% of the variability in bone density, and showed consistent, significant positive associations between bone density and serum E2 concentrations in men, even after adjustments for weight and SHBG. These data suggest that estrogens may play an important role in the development or maintenance of the male skeleton, much as is the case for the female skeleton. These data also indicate that, within the normal range, lower serum testosterone concentrations are not associated with low bone density in men.

Aged↗
PubMed1997

Essential role of POU-domain factor Brn-3c in auditory and vestibular hair cell development.

The Brn-3 subfamily of POU-domain transcription factor genes consists of three highly homologous members-Brn-3a, Brn-3b, and Brn-3c-that are expressed in sensory neurons and in a small number of brainstem nuclei. This paper describes the role of Brn-3c in auditory and vestibular system development. In the inner ear, the Brn-3c protein is found only in auditory and vestibular hair cells, and the Brn-3a and Brn-3b proteins are found only in subsets of spiral and vestibular ganglion neurons. Mice carrying a targeted deletion of the Brn-3c gene are deaf and have impaired balance. These defects reflect a complete loss of auditory and vestibular hair cells during the late embryonic and early postnatal period and a secondary loss of spiral and vestibular ganglion neurons. Together with earlier work demonstrating a loss of trigeminal ganglion neurons and retinal ganglion cells in mice carrying targeted disruptions in the Brn-3a and Brn-3b genes, respectively, the Brn-3c phenotype reported here demonstrates that each of the Brn-3 genes plays distinctive roles in the somatosensory, visual, and auditory/vestibular systems.

Animals↗
PubMed1997

The complete genome sequence of the gastric pathogen Helicobacter pylori.

Helicobacter pylori, strain 26695, has a circular genome of 1,667,867 base pairs and 1,590 predicted coding sequences. Sequence analysis indicates that H. pylori has well-developed systems for motility, for scavenging iron, and for DNA restriction and modification. Many putative adhesins, lipoproteins and other outer membrane proteins were identified, underscoring the potential complexity of host-pathogen interaction. Based on the large number of sequence-related genes encoding outer membrane proteins and the presence of homopolymeric tracts and dinucleotide repeats in coding sequences, H. pylori, like several other mucosal pathogens, probably uses recombination and slipped-strand mispairing within repeats as mechanisms for antigenic variation and adaptive evolution. Consistent with its restricted niche, H. pylori has a few regulatory networks, and a limited metabolic repertoire and biosynthetic capacity. Its survival in acid conditions depends, in part, on its ability to establish a positive inside-membrane potential in low pH.

Antigenic Variation↗
PubMed1997

Cooperative functions of the reaper and head involution defective genes in the programmed cell death of Drosophila central nervous system midline cells.

In Drosophila, the chromosomal region 75C1-2 contains at least three genes, reaper (rpr), head involution defective (hid), and grim, that have important functions in the activation of programmed cell death. To better understand how cells are killed by these genes, we have utilized a well defined set of embryonic central nervous system midline cells that normally exhibit a specific pattern of glial cell death. In this study we show that both rpr and hid are expressed in dying midline cells and that the normal pattern of midline cell death requires the function of multiple genes in the 75C1-2 interval. We also utilized the P[UAS]/P[Gal4] system to target expression of rpr and hid to midline cells. Targeted expression of rpr or hid alone was not sufficient to induce ectopic midline cell death. However, expression of both rpr and hid together rapidly induced ectopic midline cell death that resulted in axon scaffold defects characteristic of mutants with abnormal midline cell development. Midline-targeted expression of the baculovirus p35 protein, a caspase inhibitor, blocked both normal and ectopic rpr- and hid-induced cell death. Taken together, our results suggest that rpr and hid are expressed together and cooperate to induce programmed cell death during development of the central nervous system midline.

Animals↗
PubMed1997

Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL): II. Clinical efficacy and pharmacokinetics in relapsed patients.

The therapeutic effect of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL) was evaluated among 15 APL patients at relapse after all-trans retinoic acid (ATRA) induced and chemotherapy maintained complete remission (CR). As2O3 was administered intravenously at the dose of 10 mg/d. Clinical CR was achieved in nine of 10 (90%) patients treated with As2O3 alone and in the remaining five patients treated by the combination of As2O3 and low-dose chemotherapeutic drugs or ATRA. During the treatment with As2O3, there was no bone marrow depression and only limited side effects were encountered. Pharmacokinetic studies, which were performed in eight patients, showed that after a peak level of 5.54 micromol/L to 7.30 micromol/L, plasma arsenic was rapidly eliminated, and the continuous administration of As2O3 did not alter its pharmacokinetic behaviors. In addition, increased amounts of arsenic appeared in the urine, with a daily excretion accounting for approximately 1% to 8% of the total daily dose administered. Arsenic contents in hair and nail were increased, and the peak content of arsenic could reach 2.5 to 2.7 microg/g tissue at CR. On the other hand, a decline of the arsenic content in hair and nail was observed after withdrawal of the drug. We conclude that As2O3 treatment is an effective and relatively safe drug in APL patients refractory to ATRA and conventional chemotherapy.

Adolescent↗
PubMed1997

Studies comparing the kinetics of cysteine conjugation and protein binding of acetaminophen by hepatic microsomes from male mice.

A large body of evidence indicates that acetaminophen toxicity is mediated through the formation of the reactive metabolite, N-acetyl-p-benzoquinone imine (NABQI). Two assays have been employed to monitor NABQI formation by hepatic microsomes: the conjugation with a thiol trap, such as cysteine or glutathione, and the binding of NABQI to microsomal proteins. Studies from our laboratory with rat hepatic microsomes have suggested that the two assays may not be equivalent. We now find with mouse hepatic microsomes that there are also marked differences between these two assays. Among these the rate of cysteine conjugation was almost three orders of greater than that of protein binding. Furthermore, ethanol feeding increased protein binding by 97%, but cysteine conjugation by only 33%. Protein binding was linear for 20 min while cysteine conjugation was linear for only 5 min. CO, imidazole and metyrapone inhibited cysteine conjugation much more than protein binding while SKF-525A and KCN had similar effects on both reactions. Both reactions increased linearly with increasing [NADPH] up to 0.32 mM. At higher concentrations, the rate of cysteine conjugation markedly decreased while the rate of protein binding plateaued. The addition of equimolar concentrations of NADH decreased protein binding, but had no effect on cysteine conjugation. NADPH reduced the protein binding of added NABQI while NADH had little effect. The reduction of NABQI back to acetaminophen was equal for NADPH and NADH. These data indicate that the formation of the cysteine conjugate of NABQI has markedly different kinetic characteristics than the microsomal protein binding. These data might suggest that the two reactions are catalyzed in part by different isoforms of cytochrome P-450.

Acetaminophen↗
PubMed1997

Practical capillary electrophoresis method for the quantitation of the acetate counter-ion in a novel antifungal lipopeptide.

This is the first report of the validation of a capillary ion electrophoresis method for the quantitative determination of acetate (CH3COO-) levels in the acetate salt of a basic lipopeptide. The acetate counter-ion was detected using indirect photometric detection, 4.0 mM 4-hydroxybenzoic acid (HOC6H4COOH) as the carrier electrolyte and the chromophore mobile phase, and OFM Anion-BT as the electroosmotic flow (EOF) modifier. The EOF modifier is primarily a 20 mM myristyltrimethylammonium bromide (TTAB) solution. The apparent pH (pHapp) of the electrophoretic buffer was 6.0. The response was linear from 0.9 microgram/ml to 46 micrograms/ml (r2 = 0.9997). The capillary electrophoresis (CE) system is very efficient and stable, giving R.S.D. values of about 1.0% for the injection-to-infection precision without using internal standards. The method is accurate as judged by comparison to an ion-exchange HPLC method and by the 99.7% recovery of spiked acetate ion in the aqueous solution of the lipopeptide. The method is rugged with regard to critical method parameters, such as different operational voltages and effective capillary lengths. The overall precision is acceptable with a R.S.D. of 1.5% between 0.2-12% (w/w) acetate ion present in the drug substance without using an internal standard. Comparison to the ion-exchange chromatography and advantages of the CE method are discussed. This CE method has been submitted to and accepted by the regulatory agencies and is now in routine use within our laboratories.

Acetates↗
PubMed1997

Intralipid rapidly attenuates the agonist-induced activation of rat platelets in vitro.

This study examines the uptake of Intralipid by rat platelets and the effect of Intralipid on platelet activation and platelet lipid composition in vitro. 3H-cholesteryl hexadecyl ether labeled Intralipid (3H-Intralipid) was incubated with rat platelets for up to 4 hours. A significant uptake of 3H-Intralipid occurred as indicated by the increase of 3H in platelets with time. Addition of unlabelled Intralipid or chyle chylomicrons decreased the uptake of labeled Intralipid by the platelets, whereas Intralipid had less effect on the uptake of 14C linoleic acid labeled chylomicrons. Incubation of rat platelets with Intralipid caused a dose dependent inhibition of ADP, collagen and thrombin induced platelet aggregation and serotonin release. Both an attenuated response and a reduction of platelet cholesterol contents was seen within 10 minutes. Intralipid thus causes a rapid, dose- dependent inhibition of agonist-induced activation of rat platelets in vitro. This inhibition is linked to a loss of cholesterol and to an uptake of Intralipid particles by the platelets.

Animals↗
PubMed1997

Hepatocyte nuclear factor-3beta limits cellular diversity in the developing respiratory epithelium and alters lung morphogenesis in vivo.

Hepatocyte nuclear factor-3beta (HNF-3beta), a nuclear protein of the winged helix family of transcription factors, is known to play a critical role in the formation of the embryonic node, notochord, and foregut endoderm. HNF-3beta influences the expression of a number of target genes in the respiratory epithelium, activating transcription of thyroid transcription factor-1, surfactant protein-B and clara cell secretory protein. In order to discern the role of HNF-3beta in differentiation and gene expression in the lung, HNF-3beta was expressed in developing respiratory epithelial cells of transgenic mice, under the control of the human surfactant protein C gene promoter. Pulmonary abnormalities were observed in the lungs of fetal mice bearing the HNF-3beta transgene. Differentiation of distal respiratory epithelial cells was arrested in the early pseudoglandular stage. Branching morphogenesis and vasculogenesis were markedly disrupted in association with decreased E-cadherin and vascular endothelial growth factor expression. HNF-3beta limits cellular diversity of developing respiratory epithelium and alters lung morphogenesis in vivo, suggesting that precise temporal-spatial regulation of HNF-3beta expression is critical for respiratory epithelial cell differentiation and lung morphogenesis.

Animals↗
PubMed1997

Changes of phosphatidylcholine-specific phospholipase C in hepatocarcinogenesis and in the proliferation and differentiation of rat liver cancer cells.

The biological significance of phosphatidylcholine-specific phospholipase C (PC-PLC) in hepatocarcinogenesis and the proliferation and differentiation of rat liver cancer cells was investigated. The Ca2+-dependent activities of PC-PLC gradually increased during N-nitrosodiethylamine (DEN)-induced hepatocarcinogenesis and peaked at weeks 18-20 when the tumour formed. There was a close relationship between Ca2+-dependent PC-PLC activities and cellular DNA content, membranous gamma-glutamyltranspeptidase (gamma-GT), and tyrosine protein kinase. In contrast, Ca2+-independent PC-PLC activities decreased during hepatocarcinogenesis. Similarly, when CBRH-7919 rat liver cancer cells were treated with phorbol 12-myristate 13-acetate, a proliferation stimulator of the cells, gamma-GT and Ca2+-dependent activities of PC-PLC and the expression of alpha-fetoprotein increased significantly. However, when these cells were induced by retinoic acid to differentiate, Ca2+-dependent PC-PLC and gamma-GT activities decreased significantly, together with alpha-fetoprotein expression. There was a close relationship between Ca2+-dependent PC-PLC and gamma-GT activities during differentiation as there was during proliferation. We suppose that Ca2+-dependent PC-PLC is involved in rat hepatocarcinogenesis induced by DEN and that it plays an important role in the phorbol ester-induced proliferation or retinoic acid-induced differentiation of liver cancer cells.

Animals↗
PubMed1997

Cloning and expression of a novel murine semaphorin with structural similarity to insect semaphorin I.

We describe a novel semaphorin family member, Sema VIa, with 25-36% sequence identity at the amino acid level in the semaphorin domain to previously published mouse homologues. This novel family member shares considerable homology with the best characterized murine semaphorin, Sema III (also known as SemD), at the 5' end but is divergent from Sema III near the 3' end because it contains a putative transmembrane domain. Remarkably, of the known semaphorins, Sema VIa bears the greatest structural similarity to insect Sema I, although it contains a much larger intracellular domain. We propose, therefore, that Sema VIa is the prototype of a new class (class VI) of semaphorins. In order to gain insights into potential functions of Sema VIa, we have compared mRNA expression of Sema VIa to that of Sema III during development. In the nervous system, Sema VIa is expressed in strikingly localized and transient patterns that are markedly different from those of Sema III. Interestingly, Sema VIa and Sema III frequently exhibit complementary or adjacent loci of expression. We suggest that Sema VIa may be important to nervous system development via a mechanism that involves cell-cell communication.

Amino Acid Sequence↗