Search PubMed⌕ Search

Biomedical subjects

F Zhang

Publications and source records attributed to F Zhang.

At least 577 records · Page 32Linked to original sources

Oxidation chemistry of the endogenous central nervous system alkaloid salsolinol-1-carboxylic acid.

The oxidation chemistry of salsolinol-1-carboxylic acid (1), an alkaloid endogenous to the central nervous system which is elevated as a result of ethanol consumption, has been studied by electrochemical approaches at pH 7.0 in aqueous solution. The first voltammetric oxidation peak of Ia of 1 at pH 7.0 occurs at Ep = +0.116 V, indicating that this alkaloid is a very easily oxidized compound. The peak Ia reaction is a 2e-2H+ oxidation of 1 to 1,2,3,4-tetrahydro-1-methyl-1-carboxy-6,7-isoquinolinedione (8), which rapidly decarboxylates (k > 10(3) s-1) to give predominantly the quinone methide tautomer of 3,4-dihydro-1-methyl-6,7-isoquinolinediol (2). The latter compound is responsible for the second observed oxidation peak IIa observed with 1. This peak is a 2e oxidation of 2 to a quinoid intermediate (9) which can either be attacked by water to yield 3,4-dihydro-1-methyl-5,7-dihydroxyisoquinolin-6-one (13b) (which is readily further oxidized to 3,4-dihydro-1-methyl-5-hydroxyisoquinoline-6,7-dione (3)) or aromatizes to yield 1-methyl-6,7-isoquinolinediol (4). Preliminary in vivo experiments have revealed that 2 and 13b are behavioral toxins when injected into the brains of laboratory mice. The in vitro oxidation reactions of 1 and 2 reported here might be of relevance to the neurodegenerative, behavioral, and addictive consequences of chronic alcoholism.

Animals↗

Protein lateral mobility as a reflection of membrane microstructure.

The lateral mobility of membrane lipids and proteins is presumed to play an important functional role in biomembranes. Photobleaching studies have shown that many proteins in the plasma membrane have diffusion coefficients at least an order of magnitude lower than those obtained when the same proteins are reconstituted in artificial bilayer membranes. Depending on the protein, it has been shown that either the cytoplasmic domain or the ectodomain is the key determinant of its lateral mobility. Single particle tracking microscopy, which allows the motions of single or small groups of membrane molecules to be followed, promises not only to reveal new features of membrane dynamics, but also to help explain longstanding puzzles presented by the photobleaching studies, particularly the so-called immobile fraction. The combination of the two complementary technologies should measurably enhance our understanding of membrane microstructure.

Cell Membrane↗

Microvascular transplant of the gastrocnemius muscle in rats.

The rat gastrocnemius muscle can serve as a vascularized, innervated muscle transplant model. To establish the anatomic and technical details of this model, we performed ten gastrocnemius transplants and collected data on muscle weight, dimension, and vessel caliber from each muscle. The muscle, consisting of medial and lateral heads, is supplied by pairs of sural vessels averaging 0.2 mm in diameter. These vessels, however, can be taken in continuity with the femoral vessels (averaging 1.0-1.6 mm in diameter), which are used for transplantation. The muscles weighed an average of 2.8 g, and the average pedicle length was 24 mm. Eight of ten transplanted muscles were viable with intact circulation at 72 hr. The gastrocnemius transplant was technically reliable, and the muscle bulk and contour could allow biochemical and functional studies. Donor site morbidity limits this model to transplantation studies.

Animals↗

Microvascular transfer of the rectus abdominis muscle and myocutaneous flap in rats.

A rat microvascular free rectus myocutaneous flap model with a superior epigastric vessel pedicle is presented. The rectus muscle has a predictable "flow-through" axial vascular system consisting of superior and inferior epigastric vessels anastomosing under the fascial sheath, and six to seven musculocutaneous perforating branches to the skin. The superior epigastric artery and vein, averaging 0.45 mm and 0.5 mm in diameter, can be used as the vascular pedicle in muscle or myocutaneous flap transplantation. Eight muscle and 15 myocutaneous flaps were transplanted to the groin. The myocutaneous flaps averaged 3.5 cm by 1.2 cm in size; the pedicle length averaged 11 mm. The 5 day survival was 100% for muscle flaps and 67% for myocutaneous flaps. The rectus myocutaneous flap is believed to be the first true myocutaneous model in the rat.

Abdominal Muscles↗

Isolation and mapping of 45 NotI linking clones to chromosome 22.

Fifty-nine NotI linking clones have been isolated from a flow-sorted chromosome 22 cosmid library and mapped using fluorescence in situ hybridization and/or a panel of somatic cell hybrids. Fourteen clones map to the short arm of chromosome 22, 31 to the long arm, and 9 to other chromosomes; 5 clones could not be unambiguously mapped. To identify potentially informative genetic markers, the chromosome 22 clones were screened for poly(CA) sequences; 24 positively hybridizing clones, 10 on the long arm and 14 on the short arm, were identified. These clones will be useful for constructing a long-range restriction map of chromosome 22 and may facilitate the cloning of chromosome 22 genes.

Base Sequence↗

The FSH beta-subunit promoter directs the expression of Herpes simplex virus type 1 thymidine kinase to the testis of transgenic mice.

The bovine FSH beta-subunit promoter (2.3 kb) was coupled to the coding sequence of the Herpes simplex virus type 1 thymidine kinase (HSV-tk) gene and introduced into mouse embryos. A full-length tk transcript was found in the pituitary and testis. In the testis an additional truncated version of tk mRNA was also expressed. Two sets of primer extension fragments were identified, one corresponding to transcription initiation at or near the cap site of the FSH-beta gene, the other to transcription initiation within the tk gene. Furthermore, the latter, shorter transcript contained a 227 bp deletion. Only the long transcript was translated into immunoreactive tk in the later stages of developing spermatids. The tk protein was also functional in the testes, since spermatogenesis was either arrested or the germinal epithelium almost completely destroyed in transgenic males treated with the antiherpetic agent. If the FSH-beta-HSV-tk transgene also functions correspondingly in the pituitary, these mice will provide a useful model for studies on FSH.

Animals↗

Fastigial stimulation increases ischemic blood flow and reduces brain damage after focal ischemia.

Electrical stimulation of the cerebellar fastigial nucleus (FN) increases CBF and reduces brain damage after focal ischemia. We studied whether FN stimulation "protects" the brain from ischemic damage by increasing blood flow to the ischemic territory. Sprague-Dawley rats were anesthetized (halothane 1-3%) and artificially ventilated through a tracheal cannula inserted transorally. CBF was monitored by a laser-Doppler probe placed over the convexity at a site corresponding to the area spared from infarction by FN stimulation. Arterial pressure (AP), blood gases, and body temperature were controlled, and the electroencephalogram (EEG) was monitored. The stem of the middle cerebral artery (MCA) was occluded. After occlusion, the FN was stimulated for 60 min (100 microA; 50 Hz; 1 s on-1 s off) while AP was maintained at 97 +/- 11 mm Hg (mean +/- SD) by controlled hemorrhage. Rats were then allowed to recover, and infarct volume was determined 24 h later in thionin-stained sections. In unstimulated rats (n = 7), proximal MCA occlusion reduced CBF and the amplitude of the EEG. One day later, these rats had infarcts involving neocortex and striatum. FN stimulation after MCA occlusion (n = 12) enhanced CBF and EEG recovery [61 +/- 34 and 73 +/- 43%, respectively at 60 min; p < 0.05 vs. unstimulated group; analysis of variance (ANOVA)] and reduced the volume of the cortical infarct by 48% (p < 0.05). In contrast, hypercapnia (PCO2 = 64 +/- 4; n = 7) did not affect CBF and EEG recovery or infarct volume (p > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Vasodilatory action of the calcium antagonist amlodipine on large and resistance pulmonary arteries from normoxic and chronically hypoxic rats.

1. Isolated rat aorta and pulmonary arteries were maximally precontracted with 100 mmol/l KCl, and the vasorelaxation due to the dihydropyridine calcium antagonist amlodipine was measured. The response of large pulmonary arteries (mean lumen diameter 983 microns) was directly compared with that of isolated pulmonary resistance vessels (mean lumen diameter 259 microns) from both normoxic animals and animals exposed to chronic hypoxia. 2. Amlodipine caused a significant relaxation of aorta (P < 0.001). A significant relaxation of large and resistance pulmonary arteries from both normoxic and chronically hypoxic animals was also demonstrated at all doses tested (P < 0.05) or less). 3. Amlodipine produced significantly more relaxation in pulmonary resistance vessels than in large pulmonary arteries from both normoxic and chronically hypoxic rats (P < 0.02). 4. The action of amlodipine was slow in onset and persistent in all vessels studied. In the pulmonary vessels from normoxic animals both the rate of onset and the magnitude of effect was proportional to the drug concentration (P < 0.001). 5. These results demonstrate that amlodipine is a potent inhibitor of KCl-induced contractions in rat pulmonary arteries with a preferential action in pulmonary resistance vessels.

Amlodipine↗

Unconfined lateral diffusion and an estimate of pericellular matrix viscosity revealed by measuring the mobility of gold-tagged lipids.

Nanovid (video-enhanced) microscopy was used to determine whether lateral diffusion in the plasma membrane of colloidal gold-tagged lipid molecules is confined or is unrestricted. Confinement could be produced by domains within the plane of the plasma membrane or by filamentous barriers within the pericellular matrix. Fluorescein-phosphatidylethanolamine (F1-PE), incorporated into the plasma membranes of cultured fibroblasts, epithelial cells and keratocytes, was labeled with 30-nm colloidal gold conjugated to anti-fluorescein (anti-F1). The trajectories of the gold-labeled lipids were used to compute diffusion coefficients (DG) and to test for restricted motion. On the cell lamella, the gold-labeled lipids diffused freely in the plasma membrane. Since the gold must move through the pericellular matrix as the attached lipid diffuses in the plasma membrane, this result suggests that any extensive filamentous barriers in the pericellular matrix are at least 40 nm from the plasma membrane surface. The average diffusion coefficients ranged from 1.1 to 1.7 x 10(-9) cm2/s. These values were lower than the average diffusion coefficients (DF) (5.4 to 9.5 x 10(-9) cm2/s) obtained by FRAP. The lower DG is partially due to the pericellular matrix as demonstrated by the result that heparinase treatment of keratocytes significantly increased DG to 2.8 x 10(-9) cm2/s, but did not affect DF. Pericellular matrix viscosity was estimated from the frictional coefficients computed from DG and DF and ranged from 0.5 to 0.9 poise for untreated cells. Heparinase treatment of keratocytes decreased the apparent viscosity to approximately 0.1 poise. To evaluate the presence of domains or barriers, the trajectories and corresponding mean square displacement (MSD) plots of gold-labeled lipids were compared to the trajectories and MSD plots resulting from computer simulations of random walks within corrals. Based on these comparisons, we conclude that, if there are domains limiting the diffusion of F1-PE, most are larger than 5 microns in diameter.

Animals↗

Nitroprusside improves blood flow and reduces brain damage after focal ischemia.

We used the nitric oxide (NO) donor sodium nitroprusside (SNP) and the NO synthase inhibitor nitro-L-arginine methyl ester (L-NAME) to study the role of NO in the ischemic damage produced by occlusion of the rat middle cerebral artery (MCA). After MCA occlusion, intracarotid administration of SNP (2.5 mg kg h-2 for 1 h) enhanced the recovery of neocortical cerebral blood flow and of the EEG and reduced cortical infarct size by 76 +/- 2% (p < 0.01; n = 5). In contrast, administration of L-NAME (10 mg kg h-2) worsened the recovery of CBF and EEG and increased infarct size (+ 60 +/- 16%; p < 0.05; n = 5). The findings indicate that NO improves blood flow and reduces tissue damage after focal cerebral ischemia. Thus, NO donors could have an important role in the management of acute ischemic stroke.

Animals↗

Infiltrating lymphocytes and accessory cells in nasopharyngeal carcinoma.

The infiltrating lymphocytes (LCs) and accessory cells (ACs) including dendritic cells (DCs) and monocytes/macrophages in nasopharyngeal biopsies taken from 4 groups of nasopharyngeal carcinoma (NPC) patients were observed by using an immunostaining technique and the correlation of the results to the clinical manifestations and follow-up data was examined. The findings were as follows. (1) NPCs without lymph node metastasis always had marked infiltrating LCs and DCs as compared with those with lymph node(s) metastasis. (2) Advanced NPCs with lymph node(s) involvement (T1-4N1-3M0) and a rapid development of distant metastasis followed by death within 1 year after radiotherapy always showed fewer infiltrating LCs and DCs as compared with those with lymph node(s) metastasis (T1-4N1-3M0) and having longer than 5-year survival after radiotherapy. The amount of both LCs and ACs, especially DCs, infiltrating in NPC tissues appears to be an indicator of the activity of host immune defence mechanisms against cancer and influences the progression of the neoplasm as well as the prognosis.

Antigen-Presenting Cells↗

Role of nitric oxide synthase-containing vascular nerves in cerebrovasodilation elicited from cerebellum.

We studied whether the increases in cortical cerebral blood flow (CBF) elicited by stimulation of the cerebellar fastigial nucleus (FN) are attenuated by systemic administration of inhibitors of nitric oxide synthase (NOS) and, if so, whether NOS-containing perivascular nerves arising from the sphenopalatine ganglia (SPG) are the source of NO during FN stimulation. Rats were anesthetized (1-3% halothane) and artificially ventilated. The FN or the pontine reticular formation (PRF) was stimulated electrically through a stereotaxically implanted microelectrode. To eliminate the elevation in arterial pressure (AP) elicited by FN or PRF stimulation the cervical spinal cord was transected and AP was maintained by intravenous phenylephrine. CBF was measured by a laser-Doppler probe placed over the parietal cortex. Systemic administration of the NOS inhibitor N omega-nitro-L-arginine methyl ester (L-NAME; 5-40 mg/kg) reduced resting CBF, an effect that was maximal at 10 mg/kg (-30 +/- 4%; n = 6; P < 0.003, analysis of variance). L-NAME, but not its inactive isomer D-NAME, attenuated the increases in CBF elicited by FN stimulation or hypercapnia in a dose-dependent fashion (10-40 mg/kg). At 40 mg/kg, the response to FN stimulation was reduced by 80 +/- 6% (n = 6; P < 0.05) and that to hypercapnia was reduced by 70 +/- 9% (P < 0.05). In contrast, the increases in CBF elicited by PRF stimulation were not affected (10-40 mg/kg; P > 0.05; n = 6).(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗

Cerebrovasodilation elicited by fastigial stimulation is preserved under deep halothane anesthesia.

We studied the effect of halothane anesthesia on the increases in cerebral blood flow (CBF) and arterial pressure (AP) elicited by electrical stimulation of the cerebellar fastigial nucleus (FN). Rats were anesthetized (0.75-2% halothane), instrumented for continuous recording of AP, and ventilated. The FN was stimulated through stereotaxically implanted microelectrodes. In CBF experiments the elevations in AP resulting from FN stimulation were eliminated by spinal cord transection at C1. After cord transection AP was maintained by intravenous phenylephrine. CBF or cerebral glucose utilization (CGU) was measured by laser-Doppler flowmetry or the 2-deoxyglucose method, respectively. FN stimulation produced increases in CBF that were graded with the intensity (10-150 microA) or frequency (10-150 Hz) of stimulation. At 1% halothane, FN stimulation (100 microA; 75 Hz; n = 8) increased CBF by 123 +/- 16%. The elevations in CBF were attenuated by increasing levels of halothane anesthesia in a dose-dependent manner. At halothane concentrations of 1.5 and 2% the CBF response to FN stimulation (100 microA; 75 Hz) was reduced by 58 +/- 6 and 77 +/- 4%, respectively (p < 0.05 from 0.75% halothane; analysis of variance and Tukey's test). In contrast, the increases in CBF elicited by hypercapnia were not attenuated (P > 0.05 from 0.75% halothane). At 1% halothane, FN stimulation did not change CGU in neocortex (frontal cortex: unstimulated 48 +/- 6, mumol.100 g-1.min-1, FN stimulation: 47 +/- 11; P > 0.05; n = 5/group). In the group of rats in which the pressor response was studied (n = 7), halothane produced a dose-dependent attenuation of the elevations in AP. The degree of attenuation of the AP response was comparable to that of the CBF response (P > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗

Clinical and experimental studies on shallow needling technique for treating childhood diarrhea.

Treatment of diarrhea in children by shallow needling and by drugs was studied in 3 separate groups for comparison. For Group I, the lateral line II of the forehead was taken, i.e. the upper, middle and lower points of the line staring from Toulinqi (UB 15) vertically downwards to the place 1 cm below the hairline were selected. For Group II, shallow needling was done on body acupoints, the main points selected being Qihai (Ren 6), Shuifen (Ren 9), bilateral Tianshu (St 25), and bilateral Zusanli (St 36); the adjuvant acupoints were Taibai (Sp 3) and Gongsun (Sp 4). The depth of shallow needling was merely puncturing the skin. For Group III the drugs used were Liteling, Berberine, Gentamycin, Ampicillin, and SMZ Co. The results of treatment in Group I and II differed insignificantly, while both were significantly superior to drugs in Group III. Experimental studies also showed that shallow needling enhanced the humoral and cellular immunity and promoted the intestinal peristaltic function.

Acupuncture Therapy↗

The dopamine D1 receptor antagonist SCH-23390 decreases the mRNA levels of the transcription factor zif268 (krox-24) in adult rat intact striatum--an in situ hybridization study.

By in situ hybridization with an oligonucleotide probe, we have studied the cellular distribution of the messenger RNA encoding the transcription factor zif268 (krox-24) in the adult intact rat striatum and regulation of its synthesis by acute treatment with the dopamine D1 receptor antagonist SCH-23390. Zif268 mRNA was found in the striatal medium-sized neurons and not in the large cells. Its levels were decreased by SCH-23390, suggesting activation of this immediate early gene in the striatum through dopamine D1 receptor stimulation.

Animals↗

Spontaneous incorporation of the glycosyl-phosphatidylinositol-linked protein Thy-1 into cell membranes.

Thy-1 is a membrane protein that is attached to the plasma membrane by a glycosyl-phosphatidylinositol anchor. Purified rat brain Thy-1 could be reincorporated into the plasma membrane of murine Thy-1- cells directly from aqueous suspension and without the use of detergents. A peripheral staining pattern similar to that observed for endogenous Thy-1 was achieved. Treatment with phosphatidylinositol-specific phospholipase C removed nearly all antibody staining due to either endogenous or inserted Thy-1. Fluorescence recovery after photobleaching (FRAP) was used to compare the lateral mobility of endogenous and inserted Thy-1. Both forms exhibited large lateral diffusion coefficients, but with a substantial immobile fraction (approximately 50%) indicating that the immobile fraction was not due either to chemical differences between inserted and native Thy-1 or to some surface Thy-1 molecules having a protein anchor. However, the inserted Thy-1 failed to activate mouse T lymphocytes upon crosslinking as assayed by [3H]thymidine uptake. Since Thy-1 could be directly labeled with rhodamine, the effect of the size of the labeling ligand on the mobility obtained by the FRAP technique could be explored. Rhodamine-conjugated MRC-OX7 monoclonal antibody or its fragments [R-F(ab)2 or R-Fab] were compared with rhodamine as labels for Thy-1. The measured diffusion coefficients were 1.6 x 10(-9), 2.0 x 10(-9), and 3.2 x 10(-9) cm2/sec for Thy-1 labeled with R-F(ab)2, R-Fab, and rhodamine, respectively; mobile fractions were all in the 40-50% range. Thus, the size of the ligand affects the lateral mobility of this labeled membrane protein to a measurable extent.

Animals↗

Hemin-catalyzed decomposition of artemisinin (qinghaosu).

Artemisinin (qinghaosu) and its derivatives represent an important new class of antimalarial drugs. Previous work suggests that the antimalarial activity of artemisinin may be mediated by a reaction with intraparasitic hemin. Using cyclic voltammetry, artemisinin and dihydroartemisinin were irreversibly reduced at approximately -1 V. In the presence of concentrations of hemin as low as 50 nM, the reduction took place at much lower potentials (-0.435 to -0.460 V). Both reductions took place after adsorption onto the electrode surface. The shift of the reduction potential to more positive values is indicative of a catalytic process similar to that seen with hydrogen peroxide. The catalytic decomposition of artemisinin may play a role in the antimalarial activity of artemisinin.

Antimalarials↗