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Biomedical subjects

G Yang

Publications and source records attributed to G Yang.

At least 289 records · Page 16Linked to original sources
PubMed1997

Characterization of early pulmonary hyperproliferation and tumor progression and their inhibition by black tea in a 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung tumorigenesis model with A/J mice.

The pathogenesis of pulmonary tumors induced by a tobacco carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and its inhibition by black tea have been characterized. Female A/J mice (6 weeks old) were treated with a single dose of NNK (103 mg/kg of body weight, i.p.) on day 0, and the cell proliferation index was measured by the incorporation of bromodeoxyuridine (BrdUrd) immunohistochemically. The number of BrdUrd-labeled cells increased in the bronchiolar epithelium from day 2 to day 14, with the highest proliferation rate observed on day 5. By day 35, the BrdUrd-labeling index returned to the level of the control group. Further examination of the day 35 samples revealed the presence of foci of hyperproliferative cells in the bronchiolar epithelium, particularly in the bronchiolalveolar regions. These proliferating bronchiolar epithelial cells (Clara cells) may be the initiated sites for pulmonary tumorigenesis. In this short-term model, administration of black tea polyphenols (0.3%) through the drinking water starting 24 h after NNK treatment significantly inhibited NNK-induced early bronchiolar cell proliferation on day 5. In long-term studies, adenomas were observed in 100% (15 of 15) of the mice at week 16, with 7.8 +/- 0.8 tumors per mouse. At week 52, a malignant tumor incidence of 80% (41 of 51 mice) and a malignant tumor multiplicity of 2.39 +/- 0.19 were observed. The growth patterns of the malignant tumors, which included solid, papillary, and mixed types, may be associated with the cellular origin of the tumor. The cell proliferation indices, as measured by proliferating cell nuclear antigen immunohistochemistry, were significantly higher in dysplasia within adenoma than in adenoma, and significantly higher in adenoma at week 52 than in adenoma at week 16. Administration of black tea, starting 16 weeks after a single dose of NNK, inhibited the progression of adenoma to adenocarcinoma as determined by both malignant tumor incidence and multiplicity. The cell proliferation rate in adenomas was also suppressed by black tea treatment. The present work demonstrates the antiproliferative activities of black tea and its polyphenols. Such activities, at the early and late stages of lung tumorigenesis, may be important for the cancer-chemopreventive activities of black tea.

Animals↗
PubMed1997

Study of the interaction between novel ruthenium(II)-polypyridyl complexes and calf thymus DNA.

Four new complexes L2RuL'2+, where L = 2,2'-bipyridine (bpy) and 1,10-phenanthroline (phen), L' are Schiff bases or phenylhydrazones derived from 4,5-diazafluoren-9-one (AFO), were prepared. They were characterized by elemental analyses, absorption, IR, and emission spectra. The binding of these complexes to calf thymus DNA has been investigated by absorption, circular dichroism spectroscopy, and viscosity measurement. The experimental results show that the complexes bind to calf thymus DNA by three kinds of binding modes, respectively-electrostatic mode, nonintercalative binding mode, and intercalative binding mode.

2,2'-Dipyridyl↗
PubMed1997

Transmission of HIV-1 in infants born to seropositive mothers: PCR-amplified proviral DNA detected by flow cytometric analysis of immunoreactive beads.

The diagnosis of HIV infection in newborns is established by amplification of proviral DNA using the polymerase chain reaction (PCR). We developed a nonisotopic method for heminested PCR using a biotinylated primer among sets of three oligonucleotides, each selected from the HIV long terminal repeat (LTR) and gag sequences. An internal probe incorporating digoxigenin-dUTP was also synthesized by PCR. The PCR products, hybridized with LTR region or gag region probes, were captured with streptavidin-coated magnetic beads and detected by fluorescein isothiocyanate-labeled antidigoxigenin in flow cytometric analysis. This immunoreactive bead assay (PCR-IRB) detected about three copies of HIV proviral DNA. A panel of 50 coded DNA specimens of infants previously assayed by conventional PCR and with known clinical results revealed that the PCR-IRB findings using LTR, but not gag, were in agreement. A double-blind prospective study of blood samples from 14 mother-infant pairs using the PCR-IRB amplification of LTR gave results similar to the commercial Amplicor HIV-1 PCR test and were consistent with the clinical outcomes. PCR-IRB results were positive for 11 mothers and three infants, one at birth, one at 2 weeks after birth, and one at 8 weeks after birth. PCR-IRB is a simple, reliable, specific, and automatable assay useful in the early diagnosis of perinatal HIV infection in clinical practice and regional screening programs.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Active site mutants of Escherichia coli dethiobiotin synthetase: effects of mutations on enzyme catalytic and structural properties.

Five active site residues, Thr11, Glu12, Lys15, Lys37, and Ser41, implicated by the protein crystal structure studies of Escherichia coli DTBS, were mutated to determine their function in catalysis and substrate binding. Nine mutant enzymes, T11V, E12A, E12D, K15Q, K37L, K37Q, K37R, S41A, and S41C, were overproduced in an E. coli strain lacking a functional endogenous DTBS gene and purified to homogeneity. Replacement of Thr11 with valine resulted in a 24,000-fold increase in the Km(ATP) with little or no change in the Kd(ATP), KM(DAPA) and DTBS k(cat), suggesting an essential role for this residue in the steady-state affinity for ATP. The two Glu12 mutants showed essentially wild-type DTBS activity (slightly elevated k(cat)'s). Unlike wild-type DTBS, E12A had the same apparent KM(DAPA) at subsaturating and saturating ATP concentrations, indicating a possible role for Glu12 in the binding synergy between DAPA and ATP. The mutations in Lys15 and Lys37 resulted in loss of catalytic activity (0.01% and <0.9% of wild-type DTBS k(cat) for K15Q and the Lys37 mutant enzymes, respectively) and higher KM's for both DAPA (40-fold and >100-fold higher than wild-type for the K15Q and Lys37 mutant enzymes, respectively) and ATP (1800-fold and >10-fold higher than wild-type for K15Q and the K37 mutant enzymes, respectively). These results strongly suggest that Lys15 and Lys37 are crucial to both catalysis and substrate binding. S41A and S41C had essentially the same k(cat) as wild-type and had moderate increases in the DAPA and ATP KM and Kd (ATP) values. Replacement of Ser41 with cysteine resulted in larger effects than replacement with alanine. These data suggest that the H-bond between N7 of DAPA and the Ser41 side chain is not very important for catalysis. The catalytic behavior of these mutant enzymes was also studied by pulse-chase experiments which produced results consistent with the steady-state kinetic analyses. X-ray crystallographic studies of four mutant enzymes, S41A, S41C, K37Q, and K37L, showed that the crystals were essentially isomorphous to that of the wild-type DTBS. The models of these mutant enzymes were well refined (1.9 -2.6 A) and showed good similarity to the wild-type enzyme (rmsd of C alpha atoms: 0.16-0.24 A). The crystal structure of S41C complexed with DAPA, Mn2+/Mg2+, and AMPPCP revealed a localized conformational change (rotations of side chains of Cys41 and Thr11) which can account for the changes in the kinetic parameters observed for S41C. The crystal structures of the Lys37 mutant enzymes showed that the positive charge of the side chain of Lys37 is indispensable. Mutations of Lys37 to either glutamine or leucine resulted in a shift of the metal ion (up to 0.5 A) together with side chains of other active site residues which could disrupt the subtle balance between the positive and negative charges in the active site. The conformational change of the phosphate binding loop (Gly8-X-X-X-X-X-Gly14-Lys15-Thr16) upon nucleotide binding observed previously [Huang, W., Jia, J., Gibson, K. J., Taylor, W. S., Rendina, A. R., Schneider, G., & Lindqvist, Y. (1995) Biochemistry 34, 10985] appears to be important to attain the proper active site scaffold.

Adenosine Triphosphate↗
PubMed1997

C57BL/6 strain is most susceptible to cerebral ischemia following bilateral common carotid occlusion among seven mouse strains: selective neuronal death in the murine transient forebrain ischemia.

Rats and gerbils have been used widely to investigate the molecular mechanism of selective neuronal death following transient global ischemia. Recently, the availability of transgenic mice has enabled us to examine the involvement of specific gene products in various pathophysiological conditions. However, there has been only limited information about the experimental model of cerebral ischemia in mice, particularly in regard to selective neuronal death. We examined whether bilateral carotid occlusion produced global forebrain ischemia in seven common mouse strains including C57BL/6, ICR, BALB/c, C3H, CBA, ddY and DBA/2, based on neurological signs, histological findings and cortical microcirculatory as well as India ink perfusion patterns. The C57BL/6 strain was found to be the most susceptible among seven strains. All C57BL/6 mice died within 6 h after permanent bilateral carotid occlusion. After transient bilateral carotid occlusion for 20 min, more than 90% of C57BL/6 mice showed typical neurological signs such as torsion of the neck and rolling fits, and developed selective neuronal death in the hippocampus and caudoputamen. Hypothermia prevented the neuronal death. Visualization of brain vasculature by India ink perfusion indicated that the susceptibility of the mice after bilateral carotid occlusion depended mainly on the degree of anastomosis between carotid and basilar arteries. Our results showed the feasibility of investigating selective neuronal death in transgenic mice with simple temporary occlusion of both common carotid arteries, when those from the C57BL/6 strain or inbred transgenic mice from other strains with the C57BL/6 strain in a back-cross manner are used.

Animals↗
PubMed1997

Investigation of substrate activation by 4-chlorobenzoyl-coenzyme A dehalogenase.

4-Chlorobenzoyl-coenzyme A (4-CBA-CoA) dehalogenase catalyzes the hydrolysis of 4-CBA-CoA to 4-hydroxybenzoyl-coenzyme A (4-HBA-CoA), using the carboxylate side chain of aspartate 145 to displace the chloride from C(4) of the benzoyl ring. Previous UV-visible, Raman, and 13C NMR studies of enzyme-bound substrate analog or product ligand indicated that the environment of the enzyme active site induces a significant reorganization of the benzoyl ring pi-electrons. This observation was interpreted as evidence for electrophilic catalysis [viz. active-site-induced polarization of electron density away from the ring C(4)] [Taylor, K. L., Liu, R.-Q., Liang, P.-H., Price, J., Dunaway-Mariano, D., Tonge, P. J., Clarkson, J., & Carey, P. R. (1995) Biochemistry 34, 13881]. The recent crystal structure of the dehalogenase-4-HBA-CoA complex reveals two hydrogen bonds contributed to the benzoyl C=O by the backbone amide protons of Gly114 and Phe64 and a possible dipolar interaction with the positive pole of the 114-121 alpha-helix. Residues closely surrounding the benzoyl ring include W137, D145, W89, F64, F82, and H90. In the present study, the mutants D145A, H90Q, W137F, W89F, W89Y, F64L, F82L, and G114A were prepared to examine the effect of amino acid substitution on catalysis and on perturbation of the UV-visible spectral properties of the substrate benzoyl ring. Substitution of the two catalytic residues D145 and H90 inhibited catalysis but not ligand binding or the induction of the red shift in the benzoyl ring absorption. These two residues do not appear to contribute to substrate benzoyl ring binding or polarization. The F64L, F82L, W89F, and W137F mutants retained substantial catalytic activity and the ability to induce the red shift. The W89Y mutant, on the other hand, is inhibited in catalysis and ligand binding, suggesting that hydrophobicity more than packing may be critical for the benzoyl ring binding/activation. The G114A mutant was shown to be strongly inhibited in both substrate binding and activation, indicating that H-bonding and/or interaction with the dipole of the 114-121 alpha-helix may be crucial.

Acyl Coenzyme A↗
PubMed1997

B7-negative versus B7-positive P815 tumor: differential requirements for priming of an antitumor immune response in lymph nodes.

Efficient T cell activation requires two synergistic but distinct signals derived from antigenic peptides presented by the MHC and from costimulatory molecules, particularly those belonging to the B7 family. Lack of B7-CD28 interaction may cause unresponsiveness of T cells to subsequent exposure to Ag. Nevertheless, immunization by some B7- tumors induces an antitumor immune response. We found that the immune response against two B7- tumors, the mouse P815 mastocytoma and the E7C3 melanoma, requires host-derived B7, since blockage of the B7-CD28 interaction facilitates tumor growth and eliminates an antitumor response. B7 costimulation is provided in the regional, tumor-draining lymph nodes for the induction of a primary CTL response against both B7+ tumor and B7- tumor. However, the induction of a CTL response to B7+ tumors and its clonal expansion may occur at tumor sites in addition to secondary lymphoid organs so as to generate more effective tumor immunity.

Animals↗
PubMed1997

Visualization and analysis of chromatin by scanning force microscopy.

The use of the scanning force microscope (SFM) to visualize and analyze chromatin fiber structures is presented. Protocols to prepare chromatin fibers for SFM imaging of fibers in air and in buffer are first discussed. Next, the conditions for acquiring high-quality SFM images such as optimal instrumental parameters, appropriate deposition substrates, and adequate procedures of sample deposition are described. It is shown that analysis and quantitation of the SFM images support an irregular, three-dimensional arrangement of nucleosomes in the native chromatin fiber. This structure is lost in linker histone-depleted fibers, which show, instead, a beads-on-a-string structure. Molecular modeling of the chromatin fiber structures and computer simulation of the SFM imaging process indicate that the natural variability of the linker length may be the major determinant of the structural irregularity of the native chromatin fiber. Removal of linker histones (H1/H5) may change the amount of DNA wrapped around the histone octamer, which in turn may induce the transition from a three-dimensional irregular helix to an extended beads-on-a-string structure. Studies of trinucleosomes indicate that both the average successive nucleosome center-to-center distance and the average angle between two successive linkers increase upon the removal of linker histone.

Chromatin↗
PubMed1997

Phenotyping of intrahepatic and peripheral blood lymphocytes in patients with chronic hepatitis C.

The host immune responses have been suggested to play a role in liver injury occurring in patients with chronic hepatitis C. In order to explore the relationship between the relative proportions of intrahepatic and peripheral blood lymphocytes (IHL, PBL), the levels of viremia, and the histological hepatitis activity score, three-color fluorescence-activated cytometric analysis was performed for 36 patients with chronic hepatitis C and six control subjects without chronic hepatitis. The liver biopsy was performed before any antiviral therapy. Each liver specimen was divided into two parts: one for histological examination and one for immunological analysis. Tricolor CD45 was used to improve "lymphogating." Fluorescein isothiocyanate- or phycoerythrin-conjugated monoclonal antibodies with specificity for CD3, CD4, CD8, and CD20 (lymphocyte subpopulations), for CD69 (activated lymphocytes), and for CD16/56 (natural killer cells) were used. The livers of patients with chronic hepatitis C contained a greater proportion of CD4+ lymphocytes that exhibited marked expression of CD69 than in control subjects (20.7 +/- 7.3% vs 10.2 +/- 4.6%, P = 0.027). Moreover, in patients with chronic hepatitis C, the proportion of CD4+ IHL correlated with the histological hepatitis activity evaluated by the Knodell score (r = 0.48, P = 0.004). No correlation was found between the percentage of CD4+ IHL and the level of viremia or transaminase activities. Our findings clearly indicate that a cellular immune response does take place in HCV-infected livers and could thus contribute to the outcome of hepatitis C virus infection.

Adult↗
PubMed1997

Familial aggregation of oesophageal cancer in a high incidence area in China.

BACKGROUND: The high incidence of oesophageal cancer in northern China is attributed predominantly to environmental factors. The role of genetic factors has not been extensively studied. METHODS: Our aim was to study familial aggregation of oesophageal cancer in pedigrees from a defined population base in a high incidence area in China and to quantify the risk associated with different first degree relatives using different analytical approaches. Detailed data on family members of three successive generations and the occurrence of oesophageal and other cancers in family members were collected from a population-based series of 244 oesophageal cancer cases which occurred between 1987 and mid-1992 in Huixian County, Henan. RESULTS: Compared to expected rates, the standardized mortality ratio (SMR) of oesophageal cancer among first degree relatives of oesophageal cancer patients was 2.4 (2.2 in male and 2.7 in female relatives). The corresponding SMR for first and second degree relatives were 1.6 and 2.2. The null hypothesis of 'no familial aggregation' was rejected using Tarone's one-sided score test for binomial distributions indicating some evidence for clustering within families. To account for variance due to between-pairs correlation and family and/or individual specific variables, we fitted a series of regression models using a Generalized Estimation Equations (GEE) approach. The pairwise odds ratios were 2.3 for parent-parent, 1.9 for sib-parent and 1.1 for sib-sib, adjusted for sex, age and sex of index case. DISCUSSION: The existence of familial aggregation of oesophageal cancer in the study population was confirmed using different analyses and a two- to threefold increased risk was found for first degree relatives. The clear association of disease between parent and sib provides some indication of a genetic component. The pairwise association between parents but not between sibs suggests that environmental factors have a stronger action after childhood.

Aged↗
PubMed1997

A cDNA clone from a defective RNA of citrus tristeza virus is infective in the presence of the helper virus.

A naturally occurring defective RNA of 2379 nt (D2.3) from the VT strain of citrus tristeza closterovirus (CTV) was cloned and sequenced. The D2.3 RNA is a fusion of two regions of 1521 and 858 nt from the 5' and 3' ends of the CTV genome, respectively. A cDNA clone of D2.3 RNA was tagged by the insertion of a 0.47 kb chimeric DNA fragment and the recombinant cDNA was inserted downstream of the cauliflower mosaic virus 35S promoter. The resulting construct was bombarded into CTV-infected tissue, which was then grafted onto virus-free plants. The presence of recombinant RNA in systemically infected leaves was demonstrated by RT-PCR. Sequencing the RT-PCR products synthesized from double-stranded RNA confirmed the presence of the chimeric segment used for tagging. This is the first report of an infectious cDNA molecule derived from CTV D-RNA.

Base Sequence↗
PubMed1997

The investigation of 32P wire for catheter-based endovascular irradiation.

The dose distribution from a 32P source has been measured and calculated in order to evaluate its application in endovascular irradiation. The source dimension was 27 mm in length and 0.3 mm in diameter and was embedded in the end of a Ni-Ti wire. Dose measurements were performed using radiochromic film in several specially designed tissue equivalent phantoms. Loevinger's point dose kernel was used for the calculation. The approximate dose rate at a radial distance of 1.5 mm from the center of the source was found to be 6.75 cGy/s per GBq (0.25 cGy/s per mCi), which allows the delivery of a therapeutic dose in a short time interval with a satisfactory homogeneity without stepping the source. However, the dose rate falls off almost exponentially along the radial distance. Therefore it may not be suitable for treating large diameter vessel from a centrally located source. The effect of a curved 32P wire source on the radial dose distribution was also investigated. The results showed that for a maximum bend of 180 degrees the dose rate was increased by as much as 20% along the inner radial distance but decreased by as much as 20% along the outer radial distance compared to the dose along a straight wire. However, for curvatures normally encountered in a clinical situation, the dose rate was changed less than 5%.

Angioplasty, Balloon, Coronary↗
PubMed1997

Involvement of a subgenomic mRNA in the generation of a variable population of defective citrus tristeza virus molecules.

The fusion sites between the termini of naturally occurring defective RNAs (D-RNAs) from three citrus tristeza virus (CTV) isolates were sequenced. Seven of eight clones showed a common 3' terminus of 940 nucleotides (nt) fused to 5' termini with different sizes. An extra cytosine nucleotide was found at the junction site of the majority of the common 3' D-RNAs. Molecular analysis of the plus and minus strands of the 0.9-kbp double-stranded RNA, corresponding to the CTV open reading frame 11 subgenomic RNA (sgRNA), showed that they were identical in length and sequence to the common 3' sequence of the D-RNAs. These results imply that viral sgRNA messengers also function as building components for genomic rearrangement and exchange of complete viral genes.

Artificial Gene Fusion↗
PubMed1997

Immunological ignorance of an E7-encoded cytolytic T-lymphocyte epitope in transgenic mice expressing the E7 and E6 oncogenes of human papillomavirus type 16.

Certain human papillomaviruses (HPV) have been implicated in the etiology of cervical malignancies, and the E7 and E6 gene products of HPV type 16 are frequently expressed in these lesions. However, cytolytic T-lymphocyte (CTL)-mediated responses to HPV are rarely detectable in patients with cervical cancer. To examine whether the T-cell response is deficient during the HPV-induced transformation, we produced lines of transgenic (Tg) mice that expressed the E6 and E7 oncogenes in keratinized epithelia. The mice developed severe hypertrophy of all keratinized epithelia, but no malignancies were observed. Although epithelial cells from Tg mice could present at least an E7-encoded CTL epitope (E7 49-57), CTLs from these mice were neither primed to nor made tolerant of this epitope. No quantitative or qualitative differences were seen in the CTL responses of the Tg mice compared to those of their littermates following immunization with the peptide E7 49-57. Immunization of Tg mice with the E7 49-57 peptide protected them against a subcutaneous challenge with tumor cells expressing a transfected E7 gene, yet the skin was unaffected, although the cultured skin epithelial cells from Tg mice expressed E7. Our results suggest that the Tg mice were immunologically ignorant of HPV oncoproteins with respect to a CTL response and that a similar type of ignorance may explain why HPV-associated cervical cancer cells can escape immunological destruction.

Animals↗
PubMed1997

Obligatory role of NO in glutamate-dependent hyperemia evoked from cerebellar parallel fibers.

Electrical stimulation of cerebellar parallel fibers (PF) increases cerebellar blood flow (BFcrb), a response that is attenuated by glutamate receptor antagonists and NO synthase (NOS) inhibitors. We investigated whether administration of NO donors could counteract attenuation by NOS inhibitors of vasodilation produced by PF stimulation. In halothane-anesthetized rats the cerebellar cortex was exposed and superfused with Ringer solution. PF were stimulated with microelectrodes (100 microA, 30 Hz), and BFcrb was recorded by a laser-Doppler probe. During Ringer superfusion, PF stimulation increased BFcrb by 56 +/- 7% and hypercapnia by 72 +/- 5% (n = 5). Superfusion with the nonselective NOS inhibitor N-nitro-L-arginine (L-NNA, 1 mM) reduced resting BFcrb and attenuated the response to PF stimulation (-47 +/- 5%) and hypercapnia (-46 +/- 7%; PCO2 = 50-60 mmHg). After L-NNA, superfusion with the NO donors 3-morpholinosydnonimine (100 microM, n = 5) or S-nitroso-N-acetyl-penicillamine (5 microM, n = 5) reestablished resting BFcrb (P > 0.05 vs. before L-NNA) and reversed L-NNA-induced attenuation of the response to hypercapnia (P > 0.05 vs. before L-NNA) but not PF stimulation (P > 0.05 vs. after L-NNA). Similar results were obtained when NOS activity was inhibited with the inhibitor of neuronal NOS 7-nitroindazole (50 mg/kg i.p.). Like NO donors, the guanosine 3',5'-cyclic monophosphate analog 8-bromoguanosine 3',5'-cyclic monophosphate (n = 5), administered after L-NNA, restored resting BFcrb and counteracted inhibition of the response to hypercapnia but not PF stimulation. In contrast to NO donors and 8-bromoguanosine 3',5'-cyclic monophosphate, the NO-independent vasodilator papaverine (100 microM, n = 5) had no effect on attenuation of responses to PF stimulation or hypercapnia. Thus NO donors are unable to reverse the effect of NOS inhibition on vasodilation produced by PF stimulation. The data support the hypothesis that the vascular response to PF stimulation, at variance with hypercapnia, requires NOS activation and NO production. Thus NO plays an obligatory role in vasodilation produced by increased functional activity in cerebellar cortex.

Animals↗
PubMed1997

Local and propagated vascular responses evoked by focal synaptic activity in cerebellar cortex.

We investigated the local and remote vascular changes evoked by activation of the cerebellar parallel fibers (PFs). The PFs were stimulated (25-150 microA, 30 Hz) in halothane-anesthetized rats equipped with a cranial window. The changes in arteriolar and venular diameter produced by PF stimulation were measured with the use of a videomicroscopy system. Cerebellar blood flow (BFcrb) was monitored by laser Doppler flowmetry and the field potentials evoked by PF stimulation were recorded with the use of microelectrodes. PF stimulation increased the diameter of local arterioles (+26 +/- 1%, mean +/- SE) in the activated folium (n = 10, P < 0.05). The vasodilation was greatest in smaller arterioles (16.5 +/- 0.8 microm), was graded with the intensity of stimulation, and was less marked than the vasodilation produced by hypercapnia in comparably sized vessels (+58 +/- 5%, CO2 pressure = 50-60 mmHg, n = 8). In addition, the vasodilation was greatest along the horizontal beam of activated PFs and was reduced in arterioles located away from the stimulated site in a rostrocaudal direction. The increases in vascular diameter were associated with increases in BFcrb in the activated area (+55 +/- 4%, n = 5). PF stimulation increased vascular diameter (+10 +/- 0.5%, n = 10) also in larger arterioles (30-40 microm) located in the folium adjacent to that in which the PFs were stimulated. Higher-order branches of these arterioles supplied the activated area. No field potentials were evoked by PF stimulation in the area where these upstream vessels were located. The data suggest that increased synaptic activity in the PF system produces a "local" hemodynamic response mediated by synaptic release of vasoactive agents and a "remote" response that is propagated to upstream arterioles from vessels residing in the activated folium. These propagated vascular responses are important in the coordination of segmental vascular resistance that is required to increase flow effectively during functional brain hyperemia.

Animals↗
PubMed1997

The role of B7-2 (CD86) in tumour immunity.

Tumour cells engineered to express co-stimulatory molecules on their surface provide researchers with powerful new tools to manipulate antitumour responses. It has been demonstrated that B7-1+ and B7-2+ tumour cells can elicit effective responses against their wild-type counterparts. This response is primarily mediated by CD8+ cytolytic T-lymphocytes. The co-stimulatory ability of B7-2+ tumour cells is comparable to that of B7-1+ tumour cells, though with some exceptions. However, on host antigen-presenting cells (APC), B7-2 plays a dominant role in inducing T-cell-mediated immune responses. Up-regulation of B7-2 on host APC may, therefore, present an effective means of generating potent antitumour immunity.

Journal Article↗