Biomedical subjects

J Shen

Publications and source records attributed to J Shen.

At least 307 records · Page 17Linked to original sources

PubMed1997

Multistability of cognitive maps in the hippocampus of old rats.

Hippocampal neurons provide a population code for location. In young rats, environments are reliably 'mapped' by groups of neurons that have firing locations ('place fields') that can be stable for several months. Old animals exhibit deficits in spatial memory, raising the question of whether the quality or stability of their hippocampal 'cognitive maps' is altered. By recording from large groups of neurons, we observed the hippocampal spatial code to be multistable. In young rats, the place field maps were reliable both within and between episodes in a familiar environment. In old rats, place field maps were accurate and stable during an episode, but frequently exhibited complete rearrangements between episodes. In a spatial memory task, both young and old rats exhibited bimodal performance, consistent with map multistability early in training. However, the performance of young rats became almost unimodal with further training, whereas that of old rats remained markedly bimodal. The multistability of the hippocampal map provides an insight into the dynamics of neural coding in high-level cortical structures and their changes during ageing, and may provide an explanation for the frequent failure of place recognition in elderly humans.

Aging↗

PubMed1997

In vivo mechanism by which leflunomide controls lymphoproliferative and autoimmune disease in MRL/MpJ-lpr/lpr mice.

Two activities have been identified for the immunosuppressive metabolite of leflunomide, A77 1726: inhibition of dihydroorotate dehydrogenase (DHO-DHase), an enzyme involved in the biosynthesis of pyrimidine nucleotides (PyN); and inhibition of protein tyrosine kinases. The in vitro potency of A77 1726 as a DHO-DHase inhibitor is reported to be 10- to 500-fold greater than as a tyrosine kinase inhibitor. These observations suggested that the immunosuppressive efficacy of leflunomide in vivo is related to inhibition of DHO-DHase. However, observations that patients with disorders in the PyN synthetic pathway are not overtly immunodeficient militate against this hypothesis. We investigated the effects of leflunomide in vivo and report that amelioration of lymphoproliferative and autoimmune diseases in MRL/MpJ-lpr/lpr (lpr/lpr) mice by leflunomide is not accompanied by reduced PyN concentrations in lymph node cells. Our hypothesis that lymphocytes could salvage serum uridine to counter the effects of reduced PyN synthesis in vivo was supported by in vitro studies. Finally, we observed that amelioration of disease correlated with a reduction of tyrosine phosphorylated proteins in lymph node cells of lpr/lpr mice. These observations suggest that the primary mechanism by which leflunomide prevents autoimmune and lymphoproliferative diseases in lpr/lpr mice is not depletion of PyN, but correlates with reduced tyrosine phosphorylation concentrations in lymph node cells.

Aniline Compounds↗

PubMed1997

Skeletal and CNS defects in Presenilin-1-deficient mice.

Presenilin-1 (PS1) is the major gene responsible for early-onset familial Alzheimer's disease (FAD). To understand the normal function of PS1, we have generated a targeted null mutation in the murine homolog of PS1. We report that PS1-/- mice die shortly after natural birth or Caesarean section. The skeleton of homozygous mutants is grossly deformed. Hemorrhages occur in the CNS of PS1 null mutants with varying location, severity, and time of onset. The ventricular zone of PS1-/- brains is markedly thinner by embryonic day 14.5, indicating an impairment in neurogenesis. Bilateral cerebral cavitation caused by massive neuronal loss in specific subregions of the mutant brain is prominent after embryonic day 16.5. These results show that PS1 is required for proper formation of the axial skeleton, normal neurogenesis, and neuronal survival.

Alzheimer Disease↗

PubMed1997

Evidence for multiple substrate-reduction sites and distinct inhibitor-binding sites from an altered Azotobacter vinelandii nitrogenase MoFe protein.

The arginine-277 residue of the alpha-subunit of the nitrogenase MoFe protein was targeted for substitution because it is (i) a close neighbor of alpha-cysteine-275, which is one of only two residues anchoring the FeMo cofactor to the polypeptide, and (ii) a component of a potential channel for entry/exit of substrates/products and for accepting FeMo cofactor during MoFe-protein maturation. Several of the eight mutant strains constructed were capable of good diazotrophic growth and also contained FeMo cofactor as indicated by its biologically unique S = 3/2 EPR spectrum. These observations indicate that the positively charged alpha-arginine-277 residue is not required for acceptance of the negatively charged FeMo cofactor by the separately synthesized, cofactor-deficient, apo-MoFe protein. The wide range of nitrogen-fixation phenotypes shown by these mutant strains generally correlated well with their C2H2- and proton-reduction activities, which range from 5 to 65% of wild-type activity. One notable exception is the histidine-substituted strain, DJ788 (alpha-277His). This strain, although unable to fix N2 and grow diazotrophically, elaborates an altered alpha-277His MoFe protein that catalyzes the reduction of the alternative substrates, C2H2, HCN, HN3, and protons. These observations are best explained if multiple redox levels are available to the MoFe protein but the alpha-277His MoFe protein is incapable of reaching the more-reduced redox levels required for nitrogen fixation. Under nonsaturating CO concentrations, the alpha-277His MoFe-protein-catalyzed reduction of C2H2 showed sigmoidal kinetics, which is consistent with inhibitor-induced cooperativity among two C2H4-evolving sites and indicates the presence of three sites, which can be simultaneously occupied, on the MoFe protein. Similar kinetics were not observed for alpha-277His MoFe-protein-catalyzed reduction of either HCN or HN3 with nonsaturating CO levels, indicating that these substrates are unlikely to share common binding sites with C2H2. Further, CN- did not induce cooperativity in C2H2 reduction and, therefore, CO and CN- are unlikely to share a common binding site. These changed substrate specificities, reinforced by changes in the FeMo-cofactor-derived S = 3/2 EPR spectrum, clearly indicate the importance of the alpha-277 residue in catalysis and the delicate control exerted on the properties of bound FeMo cofactor by its polypeptide environment.

Arginine↗

PubMed1997

Prolongation of rat islet allograft survival by the immunosuppressive agent leflunomide.

The purpose of this study was to investigate the effect of Leflunomide (Lef), alone or in combination with a suboptimal dose of cyclosporine (CsA), on rat allogeneic islet transplantation. Two thousands islets were transplanted under the left kidney capsule of a streptozocin-induced diabetic Lewis recipient. In the ACI to Lewis combination, the mean survival time (MST) of the untreated group was 5.2 +/- 0.8 days. Lef at 2.5, 5, and 10 mg/kg/day for 14 days significantly prolonged MSTs to 19.0 +/- 1.6, 29.8 +/- 3.7, and 29.0 +/- 5.3 days (P<0.01), respectively. CsA at 5 mg/kg/day also prolonged graft survival to 21 +/- 3.5 days. When CsA (5 mg/ kg/day) was combined with Lef (5 or 10 mg/kg/day) and administered for 14 days, the survival rate of the islet allografts was further increased to 34.8 -/+ 4.7 and 36.0 -/+ 6.6 days, respectively. When Lef or CsA monotherapy was extended to 28 days at a dose of 5 mg/kg/ day, MSTs were further increased to 45.8 -/+ 8.8 or 37.4 -/+ 4.7 days, respectively. Graft MST was 56.4 -/+ 9.9 days when Lef and CsA combination therapy was administered for 28 days. In the Brown-Norway to Lewis combination, MST of the allogeneic islets in untreated rats was 6.2 -/+ 0.8 days. When Lef or CsA alone, at 5 mg/kg/day, was administered for 28 days, two of seven Lef-treated rats remained normoglycemia for more than 100 days. Graft survival longer than 100 days occurred in one of five CsA-treated rats, and in five of eight rats treated with the combination of Lef and CsA. The graft-bearing left kidney was removed after 100 days in rats with functional islet allografts, and a second Brown-Norway islet graft was transplanted into the right kidney. In all recipients, the second graft was rejected by 9.8 -/+ 1.5 days. In summary, our findings demonstrate that Lef prolonged allogeneic islet graft survival, and its immunosuppressive effect was improved when combined with CsA.

Animals↗

PubMed1997

In vivo effects of leflunomide on normal pancreatic islet and syngeneic islet graft function.

Leflunomide (Lef) is a novel immunosuppressant that can prevent islet allograft and xenograft rejection. In this study, we investigated the in vivo effects of Lef on the function of normal pancreatic islets and syngeneic islet grafts in rats and compared its effect to cyclosporine (CsA) and FK506. Different groups of rats were treated with Lef (10 and 20 mg/kg/day), CsA (20 mg/kg/day), or FK506 (2 mg/kg/day). After 4 and 6 weeks, nonfasting blood glucose (BG) levels of all the treatment groups were not different from that of the control group. Intravenous glucose tolerance test revealed that the rate of glucose disappearance was normal in Lef-treated groups. However, the rate of glucose disappearance in the CsA- and FK506-treated rats was impaired. In contrast, long-term (7 months) treatment of rats with CsA (10 mg/kg/day) resulted in five of seven rats developing hyperglycemia. However, normal BG was observed in all rats treated for 7 months with Lef (10 mg/kg/day). In the second experimental model, streptozocin-induced diabetic ACI rats were grafted with an average of 1200 syngeneic islets into the liver or kidney capsule. Diabetes in these ACI recipients was stably reversed for 6 months, then these rats were treated with Lef (20 mg/kg/day), CsA (20 mg/kg/day), and FK506 (2 mg/kg/day). After 14 days of treatment, nonfasting BG levels were significantly increased in rats treated with CsA (before: 105 +/- 2.9 mg/ dl, after: 275.8 +/- 60 mg/dl) as well as in rats treated with FK506 (before: 108 +/- 2.4 mg/dl, after: 209 +/- 10.1 mg/dl). In contrast, the BG levels of the Lef-treated rats were indistinguishable from those of the untreated control groups. Site of transplantation, i.e., liver and kidney, did not affect the results. Our results indicating that Lef has no diabetogenic property in vivo lends support to the promise that leflunomide may be effective for clinical islet transplantation.

Animals↗

PubMed1997

Synthesis of Copper Nanoparticles in Nonionic Water-in-Oil Microemulsions

Synthesis of well-dispersed copper nanoparticles was achieved by reduction of aqueous copper chloride solution using NaBH4 in the nonionic water-in-oil (w/o) microemulsions formed by Triton X-100, n-hexanol, cyclohexane, and water. It has been shown that instead of copper oxide produced in aqueous solution, metallic copper particles are formed in w/o microemulsions because of the high local copper concentration in water pools of the microemulsions, indicating the advantage offered by w/o microemulsions over aqueous phases. The absorption spectrum of the colloidal copper particles obtained in microemulsions does not exhibit the plasmon peak characteristic of the Cu surface. It is conceivable that the lack of the plasmon absorption band is attributed to the formation of a CuCl monolayer on the copper particles.

Journal Article↗

PubMed1997

A nonsense mutation due to a single base insertion in the 3'-coding region of glycogen debranching enzyme gene associated with a severe phenotype in a patient with glycogen storage disease type IIIa.

Glycogen storage disease type III (GSD-III) is an autosomal recessive disease resulting from deficient glycogen debranching enzyme (GDE) activity. A child with GDE deficient in both liver and muscle (GSD-IIIa) had recurrent hypoglycemia, seizures, severe cardiomegaly, and hepatomegaly and died at 4 years of age. Analysis of the GDE gene in this child by single-strand conformation polymorphism, followed by direct DNA sequencing and restriction analysis, revealed an insertion of a nucleotide A into position 4529 of the GDE cDNA (4529insA). This insertion resulted in substitution of a tyrosine to a stop codon at amino acid 1510 (Y1510X). The 4529insA mutation appeared to be homozygous in this patient and was not found in 20 unrelated controls or 18 other GSD-III patients (14 GSD-IIIa and 4 GSD-IIIb). This is the first identification of a disease mutation in this gene, and the data suggest that homozygous 4529insA may be associated with a severe phenotype in GSD-IIIa.

Glycogen Debranching Enzyme System↗

PubMed1997

Public housing and migration: a multi-level modelling approach.

"This paper...[analyzes] the distance moved by one-year migrants using a multi-level modelling approach. Controlling for a range of socio-economic variables, derived from the 1991 British Census Sample of Anonymised Records (SAR), at both the individual and area level, the distance moved by household heads in public, privately rented and owner-occupied housing within Britain is assessed.... It is confirmed that migrants in public housing are less likely to migrate long distances than owner-occupiers and that the proportion of public housing in a SAR area, and the absolute reduction in public housing in a SAR area between 1981 and 1991, does not have a significant effect on the distance that in-migrants have moved."

Demography↗

PubMed1997

Improvements on an in vivo automatic shimming method [FASTERMAP].

Improvements on a localized, automatic shimming method described by Gruetter and Boesch (J. Magn. Reson. 96, 323-334 (1992)) and Gruetter (Magn. Reson. Med. 29, 804-811 (1993)) are presented. A spin-echo sequence employing a double sech refocusing scheme is used to acquire a field map along linear projections that improves the signal-to-noise ratio by at least a factor of two over the stimulated echo sequence previously used. To further improve the reliability of shim adjustments, a variance-weighted polynomial regression analysis is performed. This also extends the scope of application of this technique to global shimming. Localized 1H spectra of human brain shimmed by this method are presented.

Brain↗

PubMed1997

Long-term survival of human central nervous system progenitor cells transplanted into a rat model of Parkinson's disease.

Progenitor cells were isolated from the developing human central nervous system (CNS), induced to divide using a combination of epidermal growth factor and fibroblast growth factor-2, and then transplanted into the striatum of adult rats with unilateral dopaminergic lesions. Large grafts were found at 2 weeks survival which contained many undifferentiated cells, some of which were migrating into the host striatum. However, by 20 weeks survival, only a thin strip of cells remained at the graft core while a large number of migrating astrocytes labeled with a human-specific antibody could be seen throughout the striatum. Fully differentiated graft-derived neurons, also labeled with a human-specific antibody, were seen close to the transplant site in some animals. A number of these neurons expressed tyrosine hydroxylase and were sufficient to partially ameliorate lesion-induced behavioral deficits in two animals. These results show that expanded populations of human CNS progenitor cells maintained in a proliferative state in culture can migrate and differentiate into both neurons and astrocytes following intracerebral grafting. As such these cells may have potential for development as an alternative source of tissue for neural transplantation in degenerative diseases.

Amphetamine↗

PubMed1997

Cervical cancer in young women in Taiwan: prognosis is independent of papillomavirus or tumor cell type.

The objective of this study was to address the hypotheses that younger patients with cervical cancer have a uniquely worse clinical outcome and/or are more likely to have adverse tumor cell types or specific human papillomaviruses (HPV). Cases of stage Ib-IIa cervical cancer among women 35 years of age or younger (82) and over 35 (54) were analyzed and compared with respect to the following: (1) histologic type (squamous vs nonsquamous), (2) human papillomavirus (HPV) type via polymerase chain reaction, and (3) clinical parameters, including tumor size, nodal metastases, and recurrence/persistence. Patients 35 years of age or younger had a survival similar (71.2% vs 72.4%) to that of older women from the same institution. In the younger group, outcome was not correlated with the presence or absence of HPV or HPV type. Nonsquamous carcinomas, including adenocarcinoma and small cell carcinoma, were strongly associated with HPV18, were more prevalent in the younger group, and had a slightly higher risk of recurrence/persistence; however, these differences were not significant and 71% of the recurrences were squamous cell carcinomas. Thus, in young Taiwanese women with stage Ib-IIa cervical cancer, the majority of deaths cannot be attributed to a specific HPV type or unique tumor morphology.

Adult↗

PubMed1997

Detection of serum transforming growth factor-alpha in patients of primary epithelial ovarian cancers by enzyme immunoassay.

Transforming growth factor-alpha (TGF-alpha) is a potent mitogenic polypeptide. It is secreted by a variety of transformed cells and tumors, modifying tumor growth through autocrine or paracrine mechanism. In the present study, serum levels of TGF-alpha were determined by enzyme-linked immunosorbent assay (ELISA) in 27 normal females, 116 patients with benign ovarian tumors, and 42 patients with epithelial ovarian cancers (10 with stage I, 7 with stage II, 19 with stage III, and 6 with stage IV). The ELISA assay could detect a minimum level of serum TGF-alpha concentration at 10 pg/ml. Serum samples were obtained from normal females and from patients with benign or malignant ovarian tumors before initial surgery. The detectable rates were 11% (3/27) in normal females, 28% (32/116) in benign ovarian tumors, and 62% (26/42) in ovarian cancers. The detectable rates in serous and endometrioid ovarian cancers were 71 and 70%, respectively, which were higher than the rate of 33% in mucinous type. However, there was no obvious relationship between the detectability of serum TGF-alpha and the stages of ovarian cancers. The mean concentration of TGF-alpha in ovarian cancer was 159.8 pg/ml, which was significantly higher than 27.7 pg/ml in benign ovarian tumors (P < 0.001) as well as 15 pg/ml in normal females (P < 0.001). The mean concentrations of serum TGF-alpha in stages I to IV ovarian cancers were 133.5, 96.2, 194.8, and 178.3 pg/ml, respectively. The mean concentration of serum TGF-alpha in any two stages of ovarian cancers was not statistically different. In conclusion, measurement of serum TGF-alpha can be used as a supplementary tumor marker to differentiate a malignant ovarian tumor from a benign one. However, the concentration of serum TGF-alpha has no special relation with the stage of ovarian cancer itself. Because of the small number of stage I ovarian cancers with detectable TGF-alpha in the present investigation, it would probably not be feasible to differentiate a stage I ovarian cancer from a benign ovarian tumor based only on the level of TGF-alpha in serum.

Biomarkers, Tumor↗

PubMed1997

Adiabatic slice-selective excitation for surface coils.

A novel RF pulse designed to perform a diabatic slice-selective excitation for surface coils (ASSESS) is proposed in which Bzero gradient is modulated in concert with RF frequency modulation. Within the selected slice, the principles of BIR4 pulses are employed to obtain well-defined, pure-phase and self-refocused spin rotation of arbitrary flip angles despite the presence of high B1 inhomogeneity produced by surface coils. Outside the slice, advantage is taken of the B1 field to dephase equilibrium magnetization to achieve slice selection or outer-volume suppression. This scheme should be useful for many localization techniques. Quaternion analysis of the overall propagator of the proposed pulse and numerical simulations using Bloch equations are performed. The pulse is tested experimentally on a phantom sample.

Artifacts↗

PubMed1997

Fast automatic adjustment of on-axis shims for high-resolution NMR.

A one-dimensional approach for fast, robust, automatic adjustment of on-axis shims on high-resolution NMR spectrometers based on polynomial fitting of field inhomogeneity is described. Spherical harmonic and nonspherical harmonic terms of the field distribution of shim coils are precalibrated as polynomial coefficients by successively changing shim settings. This method greatly simplifies the shim precalibration and optimization procedures and is readily to be extended to three-dimensions to include off-axis shims.

Algorithms↗

PubMed1997

Studies on the comprehensive control of babesiasis in cattle and buffaloes.

To obtain a highly effective method for controlling babesiosis in cattle and buffalo, an epidemiological survey was carried out at Zuiyun village in Hubai Province. On the grounds of the epidemiological data, control measures which included preventive drugs and killing the vectors were devised. After two years of control no clinical cases of bovine babesiosis were found. The average number of ticks on cattle or buffalo decreased from 9-282 to 0-11.3. Good results were obtained in another epidemic area using this control method. These results indicated that this technique of controlling babesiosis is highly effective.

Animals↗

PubMed1997

Studies on the relationship between urokinase plasminogen activator (uPA) and human sperm motility.

To clarify the role of urokinase plasminogen activator (uPA) in the mechanisms of regulating sperm motility and the ability of fertilizing, we investigated the quantities and activities of uPA in human seminal plasma and on the membrane of spermatozoa. Semens were harvested from 22 infertile patients with asthenospermia and 20 healthy fertile men according to WHO standards. To quantify the membrane-bound uPA in the samples, polyclonal antibodies against human urokinase were employed by means of a sandwich ELISA. The uPA activities in seminal plasma and on the surface of spermatozoa were determined using A-garose-Fibrine-Plate method and the experiment of immunological identification with polyclonal antibodies against urokinase. In lysates of spermatozoa, significantly lower levels of uPA (23.1 +/- 7.35 mu/10(6) cells) and uPA activity (5.13 +/- 3.85 mu/10(6) cells) were found in patient group as compared to healthy fertile men exhibiting normospermia (29.89 +/- 9.40 mu/10(6) cells and 10.17 +/- 6.18 mu/10(6) cells). In seminal plasma, uPA activity in patient group (2134 +/- 1581.3 IU/L) was also found significantly lower than that of normal group (3365 +/- 1859.5 IU/L). Positive correlations were observed between sperm motility and uPA quantities (r = 0.48, P < 0.005), as well as with uPA activities (r = 0.45, P < 0.005). Thus, it is inferred that membrane associated uPA on human spermatozoa may be related directly to sperm motility and fertility.

Adult↗

PubMed1997

Assessment of retrograde cardioplegia with magnetic resonance imaging and localized 31P spectroscopy in isolated pig hearts.

OBJECTIVE: This study was done to determine whether retrograde delivery of cardioplegic solution provides uniform blood flow to the myocardium supplied by an occluded coronary artery and whether it maintains myocardial energy levels beyond the coronary occlusion. METHODS: Isolated pig hearts were used. A hydraulic occluder was placed at the origin of the left anterior descending coronary artery. The perfusion pressure for retrograde delivery of cardioplegic solution was controlled at 40 to 50 mm Hg. Magnetic resonance imaging and localized 31P magnetic resonance spectroscopy were used to assess myocardial perfusion and energy metabolism, respectively. RESULTS: Magnetic resonance perfusion images (n = 7) showed that the perfusion defect that occurred during antegrade delivery of cardioplegic solution (as a result of the occlusion of the left anterior descending coronary artery) resolved during retrograde delivery of cardioplegic solution. Retrograde perfusion delivered similar amounts of flow to the jeopardized myocardium as it did to other areas of the myocardium. However, the distribution of cardioplegic solution by the retrograde route was heterogeneous (cloudlike) across both ventricular walls. 31P magnetic resonance spectra showed that the ischemic changes induced by occlusion of the left anterior descending artery during antegrade perfusion were greatly alleviated by retrograde perfusion; however, it took longer for retrograde cardioplegia (n = 7, 17.08 minutes) to restore the levels of inorganic phosphate/phosphocreatine relative to the effect of releasing the left anterior descending artery occluder during antegrade delivery of cardioplegic solution (n = 7, 5.3 minutes). CONCLUSIONS: First, retrograde delivery of cardioplegic solution provides sufficient flow to the myocardium beyond a coronary occlusion to maintain near normal levels of energy metabolites, and second, the efficacy of the retrograde route of cardioplegic solution delivery (in terms of distribution of the solution and rate of myocardial energy recovery) is significantly lower than that of the antegrade route.

Animals↗