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Biomedical subjects

F Zhang

Publications and source records attributed to F Zhang.

At least 541 records · Page 30Linked to original sources
PubMed1994

Effects of L-cysteine on the oxidation chemistry of dopamine: new reaction pathways of potential relevance to idiopathic Parkinson's disease.

Oxidation of the catecholaminergic neurotransmitter dopamine (1) at physiological pH normally results in formation of black, insoluble melanin polymer. In this study, it is demonstrated that L-cysteine (CySH) can divert the melanin pathway by scavenging the proximate o-quinone oxidation product of 1 to give 5-S-cysteinyldopamine (8). This cysteinyl conjugate is further oxidized in the presence of free CySH to give 7-(2-aminoethyl)-3,4-dihydro-5-hydroxy-2H- 1,4-benzothiazine-3-carboxylic acid (11) and its 6-S-cysteinyl (12), 8-S-cysteinyl (14), and 6,8-di-S-cysteinyl (16) conjugates in addition to many other unidentified compounds. 5-S-Cysteinyldopamine (8) and dihydrobenzothiazines 11, 12, 14, and 16 are all more easily oxidized than 1. With increasing molar excesses of CySH, the formation of melanin is decreased and, ultimately, completely blocked. Preliminary experiments have revealed that when injected into the brains of laboratory mice, dihydrobenzothiazine 11 and its cysteinyl conjugates 12 and 14 are lethal and evoke profound behavioral responses including hyperactivity and tremor. On the basis of these results and other recent observations, a new hypothesis has been advanced which might help explain the selective degeneration of nigrostriatal dopaminergic neurons which occurs in idiopathic Parkinson's Disease (PD). This hypothesis proposes that in response to some form of chronic brain insult, the activity of gamma-glutamyltranspeptidase is upregulated leading to an increased rate of translocation of glutathione (GSH) into the cytoplasm of dopaminergic cell bodies in the substantia nigra (SN) para compacta. The results of this in vitro study predict that such an elevated translocation of GSH into heavily pigmented dopaminergic neurons would cause a diversion of the neuromelanin pathway with consequent depigmentation of these cells and formation of 8, all of which occur in the Parkinsonian SN. The further very facile oxidation of 8 which must occur under intraneuronal conditions where 1 is autoxidized, i.e., in neuromelanin-pigmented cells, would lead to dihydrobenzothiazine 11 and its cysteinyl conjugates which could be the endotoxins responsible for the selective degeneration of dopaminergic SN neurons in PD. The ease of autoxidation of 8 is suggested to account for the low levels of this conjugate found in the degenerating and Parkinsonian SN.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Atomic structure of the MAP kinase ERK2 at 2.3 A resolution.

The structure of the MAP kinase ERK2, a ubiquitous protein kinase target for regulation by Ras and Raf, has been solved in its unphosphorylated low-activity conformation to a resolution of 2.3 A. The two domains of unphosphorylated ERK2 are farther apart than in the active conformation of cAMP-dependent protein kinase and the peptide-binding site is blocked by tyrosine 185, one of the two residues that are phosphorylated in the active enzyme. Activation of ERK2 is thus likely to involve both global and local conformational changes.

Adenosine Triphosphate↗
PubMed1994

The greater omentum transplantation model in the rat.

Dissection of the rat omentum were performed to study the feasibility of rat omental free transfer. The right epiploic vessels were found to be adequate for anastomosis in transfer. Twelve omental free flaps were transferred to the groin, with 100% survival of flaps in the 10 animals that survived the operation. The artery and vein averaged 0.3 and 0.4 mm in diameter, respectively. The average pedicle length was 5 mm, and the average flap weight was 136.9 mg. This omental transplant offers a new experimental means of studying lymphedema, neovascularization, and tissue revascularization.

Animals↗
PubMed1994

Pectoralis major muscle free flap in rat model.

The rat pectoralis muscle can serve as a vascularized, innervated muscle flap model. The muscle, consisting of superficialis and profundus portions, is supplied by separate neurovascular systems. The vessels to pectoralis profundus (averaging 0.3 mm in diameter) can be taken in continuity with the axillary vessels (averaging 11 mm in diameter), which are used for transplantation. The profundus portion of muscle weighed an average of 1.8 g, and the average pedicle length was 0.9 cm. Nine of 11 transplanted muscles were viable, with intact circulation at 72 hours. An example of muscle transplantation for tissue defect coverage was attempted. The pectoralis profundus transplant was technically reliable, and the muscle bulk and contour could allow biochemical and functional studies.

Abdominal Muscles↗
PubMed1994

Primary common bile duct anastomosis in the rat using microsurgical techniques.

In a rat model, we attempted to describe the natural healing course of the common bile duct (CBD) after primary microsurgical repair. Fifty-three rats were divided into experimental groups with CBD microsurgical anastomoses and control groups with CBD mobilization and ligation. Examination of three experimental groups at 1 week, 1 month, and 3 months showed evolving inflammation and stricture changes with eventual patent, healed ducts in 92% of animals at the end of 3 months following transection and repair. There were no histologic abnormalities in the livers. There were fibrotic ducts and hepatic stasis and cirrhosis changes in the control group with CBD ligation. This study demonstrates that microsurgical techniques can achieve successful primary biliary repair in the rat.

Anastomosis, Surgical↗
PubMed1994

Prolonged inhibition of brain nitric oxide synthase by short-term systemic administration of nitro-L-arginine methyl ester.

We studied the dose-response characteristics and the temporal profile of inhibition of brain nitric oxide (NO) synthase (NOS) elicited by i.v. administration of the NOS inhibitor nitro-L-arginine methyl ester (L-NAME). L-NAME was administered i.v. in awake rats equipped with a venous cannula. L-NAME was injected in cumulative doses of 5, 10, 20 and 40 mg/kg and rats were sacrificed 30 min after the last dose. NOS catalytic activity was assayed in forebrain cytosol as the conversion of [3H]L-arginine into [3H]L-citrulline. L-NAME attenuated brain NOS activity in a dose-dependent manner but enzyme activity could not be inhibited by more than approximately 50%. After a single 20 mg/kg injection of L-NAME the inhibition of brain NOS activity was time dependent and reached a stable level at 2 hrs (52% of vehicle). Inhibition after a single injection was still present at 96 hrs, albeit to a lower magnitude. We conclude that intravenous administration of L-NAME in rats at concentrations commonly used in physiological experiments leads to a dose and time-dependent but partial inhibition of brain NOS catalytic activity. The finding that the inhibition persists for several days after a single administration is consistent with the hypothesis that nitro-L-arginine, the active principle of L-NAME, binds to NOS irreversibly.

Amino Acid Oxidoreductases↗
PubMed1994

Homolateral cerebrocortical increase of immediate early gene and neurotransmitter messenger RNAs after minimal cortical lesion: blockade by N-methyl-D-aspartate antagonist.

A small surgical lesion of the parietal cortex induces an increase in the expression of several messenger RNAs varying from 172 to 980% in the entire homolateral cerebral cortex, as detected by quantitative in situ hybridization histochemistry. The messenger RNAs encoding the immediate early genes of the leucine zipper family (c-fos, c-jun, jun-B), the Zinc finger family (zif268), the glucocorticoid receptor family (NGFI-B) and the interferon family (PC4) are increased within 2 h after the lesion and return to normal levels at 6 h. The messenger RNAs encoding cholecystokinin, neuropeptide Y, somatostatin and the synthetizing enzyme of the neurotransmitter GABA, glutamate decarboxylase, are elevated within one day and return to normal levels after six days. An intraperitoneal injection of the N-methyl-D-aspartate receptor antagonist dizocilpine maleate, 30 min before surgery, prevented either the induction of immediate early gene expression or the increase of neuropeptide and glutamate decarboxylase messenger RNA expression. This study demonstrates that a minimal cortical lesion induces extensive changes in gene expression and that the mechanism(s) leading to these changes involves the action of glutamate at the N-methyl-D-aspartate receptor. These modifications may be of importance in explaining diffuse changes not related to neuronal circuitry in several conditions.

Animals↗
PubMed1994

Nitric oxide donors increase blood flow and reduce brain damage in focal ischemia: evidence that nitric oxide is beneficial in the early stages of cerebral ischemia.

We studied whether administration of nitric oxide (NO) donors reduces the ischemic damage resulting from middle cerebral artery (MCA) occlusion in spontaneously hypertensive rats (SHRs). In halothane-anesthetized and ventilated SHRs, the MCA was occluded. CBF was monitored using a laser-Doppler flowmeter. Three to five minutes after MCA occlusion, the NO donors sodium nitroprusside (SNP; 3 mg/kg/h) or 3-morpholino-sydnonimine (SIN 1; 1.5-6 mg/kg/h) were administered into the carotid artery for 60 min. As a control, the effect of papaverine (3.6 mg/kg/h), a vasodilator that acts independently of NO, was also studied. The hypotension evoked by these agents was counteracted by intravenous infusion of phenylephrine. At the end of the infusion, rats were allowed to recover. Stroke size was determined 24 h later in thionin-stained sections. In sham occluded rats, SNP (n = 5), SIN 1 (n = 5), and papaverine (n = 5) produced comparable increases in CBF (p > 0.05 from vehicle). After MCA occlusion, SNP (n = 5) and SIN 1 (n = 5), but not papaverine (n = 5), enhanced the recovery of CBF (p < 0.05 from vehicle) and reduced the size of the infarct by 28 +/- 12 and 32 +/- 7%, respectively (mean +/- SD; p < 0.05 from vehicle). To determine whether NO donors could act by inhibiting platelet aggregation, we studied the effect of SNP on collagen-induced platelet aggregation. Intracarotid administration of SNP (3 mg/kg/h for 60 min) did not affect platelet aggregation to collagen, suggesting that the protective effect of NO donors was not due to inhibition of platelet function. We conclude that NO donors increase CBF to the ischemic territory and reduce the tissue damage resulting from focal ischemia. The protective effect may result from an increase in CBF to the ischemic territory, probably the ischemic penumbra. These findings suggest that NO donors may represent a new therapeutic strategy for the management of acute stroke.

Animals↗
PubMed1994

Reduction of focal cerebral ischemic damage by delayed treatment with nitric oxide donors.

We studied whether delayed posttreatment with the nitric oxide donor 3-morpholinosydnonimine (SIN-1) is effective in reducing the size of the infarct produced by occlusion of the middle cerebral artery (MCA) in spontaneously hypertensive rats (SHRs). SHRs were anesthetized with halothane and intubated transorally. The left MCA was occluded at the level of the inferior cerebral vein. Cerebral blood flow (CBF) was monitored in the ischemic hemisphere by a laser-Doppler flowmeter, and an electroencephalogram (EEG) was recorded. SIN-1 was infused into the left internal carotid artery for 60 min starting 3, 15, 30, 60 or 120 min after MCA occlusion. The hypotension associated with SIN-1 administration was controlled by i.v. administration of phenylephrine. At the end of the infusion, rats were extubated and allowed to recover. Infarct size was measured 24 h later on thionein-stained coronal brain sections by computer-assisted planimetry. SIN-1 infusion 3 min after MCA occlusion enhanced the recovery of CBF and EEG amplitude and reduced the size of the infarct by 30 +/- 11% (p < 0.05, analysis of variance). The reduction in infarct size by SIN-1 was still seen when SIN-1 was administered 15, 30, and 60 min after MCA occlusion (p < 0.05). However, administration of SIN-1 2 h after MCA occlusion did not affect the size of the infarct (p > 0.05). We conclude that posttreatment with SIN-1 is effective in reducing focal ischemic damage if this agent is administered up to 60 min after MCA occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Detection of changes in intrathoracic fluid in man using electrical impedance tomography.

1. The Sheffield electrical impedance tomography system produces information on changes in the distribution of resistivity within tissue. We report on the assessment of electrical impedance tomography in monitoring changes in lung resistivity during a fluid challenge in normal man. 2. Eight normal subjects were studied. Electrical impedance tomography recordings were made at three different lung volumes before, during and after the intravenous infusion of 1 litre of 0.9% NaCl (saline). 3. The mean fall in lung resistivity during the infusion was -22% at total lung capacity (range -10% to -28%), -24% at tidal breathing (-15% to -37%) and -11% at residual volume (-5% to -19%) (P < 0.05 mean pre-infusion resistivity compared with the nadir value after infusion, Wilcoxon). 4. These changes in lung resistivity were probably due to a combination of a fall in haematocrit and an expansion of pulmonary blood volume.

Adult↗
PubMed1994

Microvascular vein-graft patency in the rat model.

This study establishes a controlled model, to examine the patency rates of simple, arterial and venous anastomoses, compared to vessel repairs performed with 10-mm, size-matched, interpositional, vein grafts in the rat femoral artery and vein. Patency rates in two control groups, consisting of 68 Sprague-Dawley rats in which simple, femoral-vessel repairs were performed, were compared to three experimental groups, consisting of 94 animals in which the femoral vessels were repaired with interpositional vein grafts. No statistically significant difference was found in the patency rates of arterial (p = 0.487) or venous repairs (p = 0.472) in the control groups. Nor was a significant difference found in arterial vein-graft patency (p = 0.560) or venous vein-graft patency (p = 0.862), when compared to the control groups. This study illustrates that, in the controlled laboratory setting, 10-mm, size-matched, interpositional, vein grafts have statistically the same patency rates as simple repairs of the rat femoral artery and vein.

Anastomosis, Surgical↗
PubMed1994

Microvascular vein grafts in the rat cutaneous free-flap model.

This study utilizes the rat free groin-flap model to evaluate the survival of free flaps following revascularization with interpositional vein grafts. One hundred and fifty-three Sprague-Dawley rats were divided into a control group in which the groin flap was revascularized by simple end-to-end anastomosis, and three experimental groups revascularized with 10-mm, size-matched, interpositional, vein grafts to the femoral artery (Experimental Group 1), to the femoral vein (Experimental Group 2), and to both arterial and venous femoral vessels (Experimental Group 3). No statistically significant difference was noted in survival rates, when the experimental groups were compared to the control group (p1 = 0.619, p2 = 0.677, p3 = 0.666). As demonstrated by this study, free-tissue transfers in the rat, utilizing 10-mm, interpositional, vein grafts that are size-matched, and performed in a controlled laboratory setting, have the same survival rates as those revascularized by primary arterial and venous repairs.

Anastomosis, Surgical↗
PubMed1994

A comparison of ventilatory and cardiac related changes in EIT images of normal human lungs and of lungs with pulmonary emboli.

EIT images have been recorded from the upper thorax of 10 normal subjects and from two patients with pulmonary emboli. The Sheffield Mk2 system was used to obtain the EIT images during quiet tidal breathing and the images were then analysed to extract the cardiac and respiratory related components. In the 10 normal subjects the mean measured change in resistivity during tidal breathing was 9% (SD 3%) with no significant difference in four lung regions. The mean changes during the cardiac cycle were different in the four regions, ranging from -0.9% to -2.6%. The two patients showed very different cardiac related changes from those found in the normals in the posterior lung regions. The sign of the changes was positive, whereas it was negative in the normals. The changes in the anterior lung regions were within the range found in our normal group.

Adult↗
PubMed1994

Clinical applications of electrical impedance tomography in the monitoring of changes in intrathoracic fluid volumes.

We have previously shown that EIT can detect changes in intrathoracic fluid volumes in normal subjects undergoing a fluid challenge. We now report the preliminary results of two studies designed to investigate the ability of EIT to monitor changes in intrathoracic fluid in disease states. All recordings were made using the Sheffield Mark 1 system with the 16 electrode array placed around the lower thorax. Ten patients were studied during the sequential aspiration of unilateral pleural effusions. Following recording of a baseline dataset during tidal breathing (600 cycles) fluid was aspirated in 300 ml aliquots up to a maximum of 1000 ml, 600 cycles of data being collected after each aspiration. On the side of the effusion there was a progressive increase in intrathoracic resistivity in all patients as the fluid was aspirated. The mean increase in resistivity per 100 ml aspirated was 7%, range 3%-13%, p < 0.01 pre- versus post-aspiration resistivity. In the contralateral lung there was a smaller increase in all subjects (mean 1.8%, range 1%-3%) consistent with a reduction in mediastinal shift following aspiration. In these preliminary observations we have shown that EIT can be used in the clinical environment to detect small changes in intrathoracic fluid.

Adult↗
PubMed1994

Evidence that sigma factors are components of chloroplast RNA polymerase.

Plastid genes are transcribed by DNA-dependent RNA polymerase(s), which have been incompletely characterized and have been examined in a limited number of species. Plastid genomes contain rpoA, rpoB, rpoC1, and rpoC2 coding for alpha, beta, beta', and beta" RNA polymerase subunits that are homologous to the alpha, beta, and beta' subunits that constitute the core moiety of RNA polymerase in bacteria. However, genes with homology to sigma subunits in bacteria have not been found in plastid genomes. An antibody directed against the principal sigma subunit of RNA polymerase from the cyanobacterium Anabaena sp. PCC 7120 was used to probe western blots of purified chloroplast RNA polymerase from maize, rice, Chlamydomonas reinhardtii, and Cyanidium caldarium. Chloroplast RNA polymerase from maize and rice contained an immunoreactive 64-kD protein. Chloroplast RNA polymerase from C. reinhardtii contained immunoreactive 100- and 82-kD proteins, and chloroplast RNA polymerase from C. caldarium contained an immunoreactive 32-kD protein. The elution profile of enzyme activity of both algal chloroplast RNA polymerases coeluted from DEAE with the respective immunoreactive proteins, indicating that they are components of the enzyme. These results provide immunological evidence for sigma-like factors in chloroplast RNA polymerase in higher plants and algae.

Animals↗
PubMed1994

A dual block to cell cycle progression in HL60 cells exposed to analogues of vitamin D3.

The physiologically active form of vitamin D3, 1,25-dihydroxy-vitamin D3 (1,25(OH)2D3), induces differentiation of several types of myeloid leukaemia cells. The acquisition of monocyte-like phenotype is accompanied by slower progression through the cell cycle, and G1 block has been reported to be the basis of this effect. It is shown here that human promyelocytic leukaemia HL60 cells treated with analogues of vitamin D3 which are potent inducers of monocytic differentiation have an additional cell cycle block. Exposure to 10(-7) M 1,25(OH)2D3 or 1,25-(OH)2-16-ene-D3 resulted in monocytic differentiation and the expected G1 block evident at approximately 48 h in a rapidly differentiating variant of HL60 cells (HL60-G), and at 96 h in the more slowly differentiating HL60-240 cells. In addition, a G2+M block was noted at approximately 72 h in HL60-G and HL60-240 cells. Exposure to vitamin D3 analogues also markedly increased the number of dikaryons, suggesting that cytokinesis was impaired more than karyokinesis. Treatment with a third analogue 25-hydroxy-16,23-diene-D3 produced little differentiation and had minimal effects on the cell cycle parameters. These findings indicate that vitamin D3 analogues regulate cell proliferation by control of the transition of G1 and G2+M phases, reminiscent of the cdc2/CDK2 type of cell cycle control.

Antineoplastic Agents↗