Biomedical subjects

X Wu

Publications and source records attributed to X Wu.

At least 577 records · Page 32Linked to original sources

PubMed1998

Effects of calcium and potassium supplements on arterial tone in vitro in spontaneously hypertensive rats.

1. Calcium and potassium intakes inversely correlate with blood pressure in experimental hypertension. Therefore, we examined the effects of calcium and potassium supplements alone and in combination on arterial tone in spontaneously hypertensive rats (SHR). Wistar-Kyoto (WKY) rats served as normotensive controls. Calcium and potassium contents in the control diet were both 1%, while those in supplemented chows were 3% and 3.5%, respectively. The sodium content of all diets was moderately elevated to 1.1%. 2. After 12 weeks of the study systolic blood pressures in SHR on high calcium and on high potassium diets were markedly lower (about 53 and 58 mmHg, respectively) than in hypertensive controls, while combined supplementation of these cations reduced blood pressure even further (about 69 mmHg). 3. Responses of mesenteric arterial rings in vitro were examined at the end of the study. Both high calcium and high potassium diets improved the impaired relaxation to acetylcholine (ACh) in SHR, while the combination of these supplements completely normalized this response. Cyclo-oxygenase inhibition by diclofenac augmented the relaxation to ACh in hypertensive controls but not in the other groups. Nevertheless, enhanced endothelium-mediated dilatation was still observed in the presence of diclofenac and the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) in all supplemented groups. Interestingly, additional blockade of Ca2+-activated K+ channels by tetraethylammonium abolished the improved relaxation to ACh in SHR on high calcium and on high potassium, but distinct responses were still observed in WKY rats and SHR on the combined supplement. 4. When hyperpolarization of smooth muscle was prevented by precontraction of the preparations with 50 mM KCl, only marginal differences were observed in the diclofenac and L-NAME-resistant relaxations to ACh between the study groups. Finally, endothelium-independent vasorelaxations of noradrenaline-precontracted rings to nitroprusside, isoprenaline and cromakalim were comparably augmented by all supplements. 5. In conclusion, the vascular mechanisms underlying the antihypertensive effect of high calcium and high potassium diets during moderately elevated sodium intake in SHR may involve enhanced arterial hyperpolarization, increased smooth muscle sensitivity to nitric oxide and decreased production of vasoconstrictor prostanoids. The administration of these cations in combination was more effective than either of them alone in reducing blood pressure and restoring arterial tone.

Animals↗

PubMed1998

Control of arterial tone after long-term coenzyme Q10 supplementation in senescent rats.

1. Age-associated deterioration of arterial function may result from long-lasting oxidative stress. Since coenzyme Q (Q10) has been suggested to protect the vascular endothelium from free radical-induced damage, we investigated the effects of long-term dietary Q10 supplementation on arterial function in senescent Wistar rats. 2. At 16 months of age, 18 rats were divided into two groups. The control group was kept on a standard diet while the other group was supplemented with Q10 (10 mg kg(-1) day(-1)). In addition, nine rats (age 2 months) also ingesting a standard diet were used as the young control group. After 8 study weeks the responses of the mesenteric arterial rings in vitro were examined. 3. Endothelium-independent arterial relaxations to isoprenaline and nitroprusside (SNP) were attenuated in aged rats. Increased dietary Q10 clearly enhanced the relaxation to isoprenaline, but did not affect the response to SNP. In addition, vasodilation of noradrenaline-precontracted rings to acetylcholine (ACh), which was also impaired in aged vessels, was improved after Q10 supplementation. Cyclooxygenase inhibition with diclofenac enhanced the relaxation to ACh only in young rats, while it abolished the difference between the old controls and Q10 supplemented rats, suggesting that the improved endothelium-dependent vasodilation observed in Q10 supplemented rats was largely mediated by prostacyclin (PGI2). 4. In conclusion, long-term Q10 supplementation improved endothelium-dependent vasodilation and enhanced beta-adrenoceptor-mediated arterial relaxation in senescent Wistar rats. The mechanisms underlying the improvement of endothelial function may have included augmented endothelial production of PGI2, increased sensitivity of smooth muscle to PGI2, or both.

Acetylcholine↗

PubMed1998

A FISH cosmid 'cocktail' for detection of 13q deletions in chronic lymphocytic leukaemia--comparison with cytogenetics and Southern hybridization.

The most frequent structural chromosome abnormality in chronic lymphocytic leukaemia (CLL) is deletion at chromosome 13q14. Studies with Southern blot hybridisation have revealed deletions in the region located telomeric of the retinoblastoma gene in more than 40% of cases. The highest frequency of homozygous deletions has been found at the D13S319 locus and it is likely that a new tumour suppressor gene is located close to this region. We have analysed deletions in the D13S319 region in 20 selected CLL patients using conventional cytogenetic analysis, fluorescence in situ hybridisation (FISH) and Southern blot hybridisation. FISH and Southern hybridisation are equally efficient in detecting deleted clones in our study. However, FISH analysis indicate that subclones with different numbers of alleles in the D13S319 region can exist simultaneously. The cytogenetic analyses confirm that clones with different chromosomal abnormalities can occur in patients with CLL and that 13q14 deletions can be limited to one of these subclones. Furthermore, the FISH analyses show that trisomy 12 and deletion of 13q14 can occur in the same cell clone. Finally, our study confirms that mitogen stimulation of peripheral blood cells from CLL patients before FISH analysis may result in a sharp increase in normal appearing cells, which can hide leukaemic clones with deletions in the D13S319 region.

Blotting, Southern↗

PubMed1998

Estrogen profiles in postmenopausal African-American women in a wheat bran fiber intervention study.

High dietary fiber intake has been hypothesized to lower blood estrogen concentrations, an effect thought to be beneficial for decreasing breast cancer risk. This study investigated the association between dietary supplementation of wheat bran and circulating estrogen levels in postmenopausal African-American women participating in a community intervention trial. Seventeen postmenopausal women (aged 63 +/- 1.6 yr) participated in the study. Nutritional status was assessed and blood and 24-hour urine samples were collected before and after five to six weeks of daily supplementation of the diet with 35 g of wheat bran cereal (11.6 g insoluble dietary fiber) marked with 28 mg of riboflavin. Riboflavin confirmed that all postmenopausal participants adhered to the intervention protocol. Nine of the 17 postmenopausal women were taking some form of estrogen replacement therapy (PM-ERT). Baseline hormone levels in the PM-ERT group did not significantly change after the dietary intervention. Estradiol (96.8 +/- 20.3 vs. 113.8 +/- 23.3 pg/ml), androstenedione (0.47 +/- 0.06 vs. 0.45 +/- 0.06 ng/ml), and sex hormone-binding globulin (SHBG, 107 +/- 13.5 vs. 106.6 +/- 13.3 nmol/l) levels remained constant. In the eight postmenopausal women who were not receiving exogenous hormones (PM), wheat bran consumption was not associated with predicted decreased levels of estradiol (25.7 +/- 2.7 vs. 31.0 +/- 1.9 pg/ml), estrone (38.3 +/- 10.1 vs. 39.3 +/- 10.6 pg/ml), and androstenedione (0.78 +/- 0.08 vs. 0.68 +/- 0.11 ng/ml) or with increased concentrations of SHBG (35.2 +/- 6.4 vs. 34.8 +/- 6.5 nmol/l). Participants receiving ERT had baseline and postintervention levels of estradiol and SHBG significantly higher and androstenedione significantly lower than those not receiving ERT. No association between wheat bran supplementation and hormone levels was found in PM or PM-ERT African-American participants. These results in postmenopausal women are in contrast to findings of earlier studies in premenopausal women indicating that wheat bran fiber decreases serum sex hormones. Estrogen levels in postmenopausal women are only 5-10% of those in premenopausal women; therefore, a high wheat bran fiber diet alone may not be sufficient to depress these low levels even further.

Aged↗

PubMed1998

Deletion in poly(ADP-ribose)polymerase pseudogene and lung cancer risk.

The poly(ADP-ribose)polymerase (PADPRP) gene has been implicated in carcinogenesis through its role in DNA repair, replication and recombination. A two-allele polymorphism in the chromosome 13 PADPRP pseudogene has been studied in several racial groups. It has been suggested that the B allele, which results from a 193-bp deletion in the gene, predisposes to myeloma in Blacks. We assessed the association between chromosome 13 PADPRP pseudogene genotype, mutagen sensitivity (a marker reflecting host DNA repair capability), cigarette smoking, and lung cancer risk in a minority lung cancer case-control study. The chromosome 13 PADPRP pseudogene polymorphism was detected by polymerase chain reaction-based analysis. Mutagen sensitivity was measured by an in vitro assay that quantified bleomycin-induced chromatid breaks in peripheral blood lymphocyte cultures. We examined 121 cases (80 African-Americans and 41 Mexican-Americans) with previously untreated lung cancer and 171 matched controls. Our results suggested that the distribution of the PADPRP pseudogene genotype frequencies was significantly different among African-American and Mexican-American controls (P < 0.001). The susceptibility genotype (i.e. at least one B allele) was found in 82.5% of African-American cases, 79.4% of African-American controls, 53.7% of Mexican-American cases, and 32.4% of Mexican-American controls. The odds ratios (OR) and 95% confidence intervals for the PADPRP susceptibility genotypes were 2.3 (95% CI = 0.7-8.0) and 3.2 (95% CI = 1.0-10.3) for African-Americans and Mexican-Americans respectively, after adjustment by age, sex, pack-years and mutagen sensitivity. Patients with the susceptibility genotype appeared to have more mutagen-induced breaks than did patients with the other genotype. Only adenocarcinoma was significantly associated with the PADPRP susceptibility genotype (OR = 3.8). Mutagen sensitivity (> or = 1 break/cell) was significantly associated with lung cancer risk for both ethnic groups with increased ORs of above three-fold. On stratified analysis, synergistic interactions were noted for the PADPRP susceptibility genotype, mutagen sensitivity and smoking status. In Mexican-Americans, the ORs for PADPRP susceptibility genotype, mutagen sensitivity and both risk factors combined were 1.3, 2.7 and 17.1 respectively. The combined OR for the PADPRP susceptibility genotype and smoking status was 15.6. Therefore, this polymorphism appears to be associated with lung cancer risk. However, it is likely that no single genotype is sufficiently predictive of risk and that a panel of susceptibility markers is needed to define the high-risk subgroup.

Black People↗

PubMed1998

Repair of DNA lesions induced by polycyclic aromatic hydrocarbons in human cell-free extracts: involvement of two excision repair mechanisms in vitro.

Polycyclic aromatic hydrocarbons (PAHs) are significant environmental pollutants representing an important risk factor in human cancers. DNA adducts formed by the ultimate carcinogens of PAHs are potentially toxic, mutagenic and carcinogenic. DNA repair represents an important defense system against these genotoxic insults. Using a human cell-free system we have examined repair of DNA lesions induced by several PAH dihydrodiol epoxides, including anti-(+/-)-benzo[a]pyrene-trans-7,8-dihydrodiol-9,10-epoxide, anti-(+/-)-benz[a]anthracene-trans-3,4-dihydrodiol-1,2-epoxide, anti-(+/-)-benz[a]anthracene-trans-8,9-dihydrodiol-10,11-epoxide, anti-(+/-)-benzo[b]fluoranthene-trans-9,10-dihydrodiol-11,12-epoxide and anti-(+/-)-chrysene-trans-1,2-dihydrodiol-3,4-epoxide. Effective repair of DNA damage induced by these five PAH metabolites was detected. Two distinct mechanisms of excision repair were observed. The major repair mechanism is nucleotide excision repair (NER). The other mechanism is independent of NER and correlated with the presence of apurinic/apyrimidinic sites in the damaged DNA, thus presumably reflecting base excision repair (BER). However, the contribution of BER to different PAH lesions varied in vitro. These results suggest the possibility that BER may also play an important role in repair of certain PAH-induced DNA lesions.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

PubMed1998

Novel mutations in the RAD3 and SSL1 genes perturb genome stability by stimulating recombination between short repeats in Saccharomyces cerevisiae.

Maintaining genome stability requires that recombination between repetitive sequences be avoided. Because short, repetitive sequences are the most abundant, recombination between sequences that are below a certain length are selectively restricted. Novel alleles of the RAD3 and SSL1 genes, which code for components of a basal transcription and UV-damage-repair complex in Saccharomyces cerevisiae, have been found to stimulate recombination between short, repeated sequences. In double mutants, these effects are suppressed, indicating that the RAD3 and SSL1 gene products work together in influencing genome stability. Genetic analysis indicates that this function is independent of UV-damage repair and mutation avoidance, supporting the notion that RAD3 and SSL1 together play a novel role in the maintenance of genome integrity.

Adenosine Triphosphatases↗

PubMed1998

Relationship between lung function and blood pressure in Chinese men and women of Beijing and Guangzhou. PRC-USA Cardiovascular and Cardiopulmonary Epidemiology Research Group.

BACKGROUND: Previous studies of western populations have shown an inverse association between lung function and blood pressure. METHODS: As part of a People's Republic of China-United States cardiopulmonary epidemiology study, we investigated the cross-sectional relationship between lung function and blood pressure in 6757 Chinese men and women, aged 35-54, from Beijing and Guangzhou, China. We also evaluated the longitudinal association between lung function and incident hypertension among 4818 initially normotensive subjects followed up between 2 and 4 years later. RESULTS: In our cross-sectional analyses of baseline data, lung function varied inversely with baseline systolic (SBP) and diastolic blood pressure (DBP) in all women and in Beijing men. This association held for absolute and height-standardized forced vital capacity (FVC) and one-second forced expiratory volume (FEV1) (correlations: 0.10, -0.18, P < 0.0001), but was weaker after adjustment for age (correlations: -0.02, -0.11). The longitudinal follow-up showed that lower initial lung function levels were associated with a higher incidence of hypertension (SBP > or = 140 mmHg or DBP > or = 90 mmHg or currently using antihypertensive medications), but only among women in Guangzhou. Relative risks for hypertension incidence for those in the two lowest quintiles for FEV1 and FVC, compared to those in the two highest quintiles, ranged from 1.9 to 2.3 for Guangzhou women and from 0.9 to 1.4 for all other gender-city subgroups. Logistic regression analyses adjusting for age, baseline SBP, body mass index, smoking, education, and urban versus rural setting generally confirmed these patterns. CONCLUSIONS: These results suggest a statistically significant, though weak, inverse relationship between lung function and blood pressure in Chinese men and women. This association is largely attributable to age and is present prospectively only in women.

Adult↗

PubMed1998

Complement-mediated cytolysis and azidothymidine are synergistic in HIV-1 suppression.

Some normal human sera contain a natural IgM antibody against gangliotetraose and GM2 which is capable of initiating complement-mediated cytolysis of HIV-1-infected cells. A potent cytolytic serum (lytic serum) harboring this antibody also caused lysis of HIV-1 virions. When lytic serum was added to a mixed culture of HIV-infected cells and naive cells at a ratio of 1:100, expansion of HIV-1 infection was postponed by 1 week. Furthermore, the co-presence of both the lytic serum and azidothymidine continued to significantly suppress infection, even after 4 weeks of cultivation.

Anti-HIV Agents↗

PubMed1998

Transient global forebrain ischemia induces a prolonged expression of the caspase-3 mRNA in rat hippocampal CA1 pyramidal neurons.

The authors recently cloned a cDNA for an ICE/CED3-related cysteine protease from rat brain, which is closely related to human CPP32 (now designated caspase-3). In situ hybridization histochemistry revealed a profound developmental regulation of the caspase-3 transcript in rat brain, with relatively high levels of caspase-3 mRNA observed in neurons of the fetal and neonatal brain and low levels of mRNA in neurons of the adult brain. The authors report that transient forebrain ischemia, which results in a delayed apoptotic death of CA1 pyramidal neurons, results in prolonged expression of caspase-3 mRNA in these same pyramidal neurons. Up-regulation of caspase-3 mRNA in CA1 pyramidal neurons is prominent 24 hours after transient global ischemia, and expression is maintained at higher levels for at least 72 hours after ischemia. However, by 96 hours after ischemia, a marked decrease in caspase-3 mRNA expression is observed in CA1 pyramidal neurons, showing severe degenerative changes (e.g., nuclear condensation). By contrast, there is no change in the expression of a closely related member of caspase family, caspase-2, in CA1 pyramidal neurons after global ischemia. Instead, caspase-2 mRNA is induced in lamina layers of cerebral cortex 24 hours after the ischemia. A selective and prolonged induction of the caspase-3 gene in committed CA1 pyramidal neurons suggests that transcriptional activation of this caspase-3 gene may be involved in the apoptotic cell death cascade of CA1 neurons after transient global ischemia.

Animals↗

PubMed1998

Evidence that assembly of a potyvirus begins near the 5' terminus of the viral RNA.

A search for the first region in the genomic RNA of a potyvirus to be encapsidated during the assembly of virus particles in vivo has been undertaken. Protoplasts were collected at various times after inoculation and fragments of viral RNA that were protected from nuclease degradation were isolated from extracts and identified by RT-PCR procedures. Nuclease-resistant fragments of viral RNA were not detected in protoplasts that had been infected for 30 min. However, such fragments were present in protoplasts collected 40 min after inoculation and these contained a region at or near the 5' terminus of the viral RNA. Protoplasts that had been infected for 45 min or longer contained full-length viral RNA in a nuclease-resistant form. These results suggest that assembly of virus particles begins with the interaction of coat protein subunits with the 5' terminal region of progeny viral RNA molecules.

Binding Sites↗

PubMed1998

Regulation of the cross-bridge cycle: the effects of MgADP, LC17 isoforms and telokin.

This review summarizes the role of MgADP in force maintenance by dephosphorylated cross-bridges in smooth muscle and a potential physiological role for telokin. In tonic, compared with phasic, smooth muscles the affinity of cross-bridges in approximately 5 times higher for MgADP and the apparent second-order rate constant for MgATP is approximately 3 times lower. This gives rise to a large population of dephosphorylated cross-bridges in tonic smooth muscle. Such cross-bridges are thought to be major determinants of the different relaxation kinetics of the two types of smooth muscle and contribute to force maintenance at low levels of MLC20 phosphorylation, termed 'catch-like state' (Somlyo & Somlyo 1967) or 'latch' (Dillon et al. 1981). The molecular basis of the different affinities for MgADP and MgATP between tonic and phasic smooth muscle myosin was explored by exchange of essential myosin light chain (LC17) isoforms. In phasic bladder smooth muscle the exchange of LC17b for LC17a caused a significant decrease in the unloaded shortening velocity of non-phosphorylated, slowly cycling cross-bridges, suggesting that the LC17 isoforms contribute to the nucleotide affinity of latch bridges. The role of telokin in Ca(2+)-desensitization in phasic smooth muscle is reviewed. Telokin, the independently expressed C-terminus of myosin light chain kinase, is extensively phosphorylated during forskolin- and 8-br-cGMP-induced relaxation in situ. Telokin accelerated dephosphorylation of the regulatory myosin light chain and relaxed rabbit ileum smooth muscle. The results suggest that telokin contributes to cAMP and/or cGMP kinase-mediated Ca(2+)-desensitization of phasic smooth muscles.

Adenosine Diphosphate↗

PubMed1998

Variations of arterial responses in vitro in different sections of rat main superior mesenteric artery.

We examined the control of vascular tone in rat main superior mesenteric artery. Three standard rings (3 mm in length) of the mesenteric artery were cut, beginning 5 mm, 13 mm and 21 mm distally from the mesenteric arteryaorta junction. In noradrenaline-precontracted rings, relaxations to acetylcholine in the absence and presence of the cyclooxygenase inhibitor diclofenac, did not differ in the studied sections. However, the nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester, attenuated the diclofenac-resistant responses to acetylcholine more effectively in the proximal than the distal section. Glibenclamide, an inhibitor of ATP-sensitive K+ channels, diminished relaxations evoked by acetylcholine only in the distal section, whereas the inhibitor of Ca2+ activated K+ channels, apamin, attenuated the responses in all sections. Furthermore, relaxation sensitivity to nitroprusside and isoprenaline was lower in the proximal than distal section. Arterial contractile sensitivity to noradrenaline and potassium chloride was higher, while the maximal contractile force generation was lower in the proximal than the distal part. In conclusion, in different sections of rat main superior mesenteric artery considerable variability was observed in vasoconstrictor and vasodilator responses, as well as in the contribution of endothelial nitric oxide and endothelium-mediated hyperpolarization to vasodilation. Therefore, the present results emphasize the fact that only corresponding vessel segments should be used when investigating the control of arterial tone.

Animals↗

PubMed1998

Accumulation of bisphosphonates in human artery and their effects on human and rat arterial function in vitro.

Clodronate, etidronate and pamidronate are bisphosphonates introduced in the treatment of hypercalcaemia and osteoporosis. Interestingly, they also inhibit development of experimental atherosclerosis and affect smooth muscle tone of isolated rat tail artery. We have studied in vitro whether these hydrophilic compounds 1) accumulate in the wall of the human artery, 2) influence human arterial tone, and 3) interfere with the vascular action of L-type Ca2+ antagonists. Human internal mammary artery rings were incubated with 14C-labelled bisphosphonates. After a 2-hr incubation, the ratios of artery-to-incubate concentrations with 4 and 40 mumol/l of clodronate were, respectively, 3.0 +/- 0.5 (mean +/- S.E.M.) and 1.3 +/- 0.2, with 4 and 40 mumol/l of etidronate 7.4 +/- 0.9, and 3.2 +/- 0.4, and with 0.4 and 4 mumol/l of pamidronate 4.7 +/- 0.7 and 3.9 +/- 0.8. Both tested bisphosphonates, clodronate and pamidronate, reduced the arterial contractile force induced by alpha-adrenergic stimulation with noradrenaline and membrane depolarization with high concentration of KCl. Clodronate also decreased the arterial contraction induced by cumulative addition of Ca2+ with KCl as the agonist, and had an additive inhibitory effect on this response with the L-type Ca2(+)-channel blocker nifedipine. The results demonstrate that 1) bisphosphonates accumulate markedly in human artery, 2) clodronate and pamidronate reduce human arterial contactile force to alpha-adrenergic and depolarizing stimuli, and 3) as shown with clodronate, bisphosphonates may exert an additive inhibitory effect on human arterial contractions with an L-type Ca2(+)-channel blocker.

Animals↗

PubMed1998

Bladder and rectal doses from external-beam boosts after gynecologic brachytherapy.

PURPOSE: To establish a typical value for radiation doses under pelvic midline shields. MATERIALS AND METHODS: Three methods were used to determine bladder and rectal doses under 5- or 6-half-value layer (HVL) shields for 10- and 24-MV external beams. First, dose was computed with a standard irregular field routine in 25 consecutive patients (aged 35-70 years) with stage IIB or IIIB disease treated with cesium-137 brachytherapy followed by a parametrial external-beam boost. Second, in vivo measurements with a solid-state probe were recorded during the first boost after completion of brachytherapy in each patient. Third, measurements obtained with an ionization chamber in a solid phantom (water-equivalent material) were compared with computed and in vivo results. RESULTS: All three dosimetric methods yielded bladder and rectal doses higher than the commonly assumed 5% of the unshielded primary beam dose. Doses within the shielded volume may be as high as 15% of the unshielded dose. Doses are similar under 5- and 6-HVL midline shields. Often, the actual bladder and rectal doses exceeded the planned dose limits and their corresponding maximum radiation dose tolerance levels. CONCLUSION: Bladder and rectal doses are higher than previously understood. Parametrial boosts may contribute as much as 3.0 Gy to the bladder and rectal doses.

Adult↗

PubMed1998

Influence of gender on control of arterial tone in experimental hypertension.

Endothelial dysfunction has been found to be less severe in female than in male spontaneously hypertensive rats (SHR), which could contribute to the gender differences observed in the extent and rate of progression of hypertension in SHR. However, the influence of gender on the roles of different endothelium-derived mediators in the arterial responses in hypertension have not been evaluated in detail. Therefore, contractile and relaxation responses of mesenteric arterial rings in vitro were studied in female and male SHR, with normotensive female and male Wistar-Kyoto rats (WKY) serving as controls. In norepinephrine (NE)-precontracted arterial rings, endothelium-dependent relaxations to ACh as well as endothelium-independent dilations to sodium nitroprusside were more pronounced in female than in male SHR, whereas relaxations to the beta-adrenoceptor agonist isoproterenol remained equally impaired in female and male SHR. The cyclooxygenase inhibitor diclofenac, which reduces the synthesis of dilating and constricting prostanoids, markedly enhanced the relaxations to ACh in male SHR but not in the other groups. The nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester attenuated the relaxations to ACh more effectively in female SHR and WKY than in the male groups. However, when endothelium-dependent hyperpolarization was prevented by precontracting the preparations with KCl, no significant differences were found in relaxations to ACh among the study groups. In conclusion, release of cyclooxygenase-derived constricting factors appeared to be more pronounced in male than in female SHR. In addition, the relative role of NO in endothelium-dependent arterial relaxation seemed to be higher in female than in male SHR, and relaxation induced by an NO donor also was more pronounced in female than in male SHR.

Acetylcholine↗

PubMed1998

Gamma knife radiosurgery for large volume brain tumors: an analysis of acute and chronic toxicity.

Gamma Knife radiosurgery is often used to treat intracranial tumors <4 cm (approximately 13.5 cm3) in mean diameter. Larger lesions are rarely treated because of the expectation that increasing target volume will increase toxicity. We retrospectively analyzed 35 patients with primary or metastatic brain tumors of more than 13.5 cm3 treated with the Gamma Knife. Only 3 (8.5%) patients developed acute clinical toxicity. Nine (25%) patients developed post-Gamma Knife radionecrosis based on imaging studies, with only 3 of these patients (9% of the study population) having clinical progression of symptoms. Necrosis was not found to be related to prescribed dose, treatment volume or number of treated isocenters. We found no undue toxicity from the treatment of large brain tumors with the Gamma Knife.

Acute Disease↗

PubMed1998

Dose volume histogram analysis of the gamma knife radiosurgery treating twenty-five metastatic intracranial tumors.

Treating multiple brain metastatic sites in Gamma Knife radiosurgery is not uncommon. Most metastases can be treated with few or even one single shot. Occasionally we have patients returning for retreatment for different intracranial metastatic sites at different times. Dose distribution for these metastases are prescribed locally without considering the previous dose contribution. We present a study which simultaneously calculates the dose distribution of 25 randomly placed shots distributed inside the intracranial region. The Dose Volume Histogram (DVH) is plotted to study the coverage of the tumor sites and normal tissues. We have calculated ten DVH studies and show that 50% of the brain volume receives less than 500 cGy for the maximum tumor dose of 40 Gy, and the dose gradient is extremely steep. This DVH analysis shows that the Gamma Knife radiosurgery is a good treatment modality to control the local tumors while maintaining normal brain function, even for the large number of brain metastasis treated at different times.

Brain↗