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PubMed1995

Changes in the hepatitis B virus precore and core regions in association with the disappearance of hepatitis B e antigen in patients with chronic hepatitis B.

Disappearance of the hepatitis B e antigen (HBeAg) typically signals the remission of chronic hepatitis B; however, HBeAg defective variants have been identified in patients with HBeAg negative chronic hepatitis (CH). We studied the changes in the hepatitis B virus (HBV) genome associated with HBeAg clearance in four asymptomatic carriers (ASC) and in four patients with CH. Three ASC had a precore stop codon variant with the core region being wild-type or deleted. The other ASC had wild-type precore and core region. In all ASC, HBV levels were reduced markedly with two ASC converting HBV negative status via polymerase chain reaction. In contrast, patients with CH had continued high titers of HBV. In two patients, the precore region remained wild-type, but the core region contained a cleavage site mutation or was deleted. The precore variant was present in both ASC and CH, perhaps suggesting that it does not significantly influence hepatitis B activity.

Adult↗

PubMed2004

Vitamin C: basic metabolism and its function as an index of oxidative stress.

Vitamin C (ASC) is well known as an outstanding antioxidant in animal tissues. This concept is reviewed from a chemical standpoint, starting from a chemical view of radical reactions in the cell. ASC, vitamin E, and lipid hydroperoxide were selected as key molecules involved in radical reactions in the cell, and their efficiencies as an index of oxidative stress were evaluated. At first, methods for specific and sensitive determination of ASC and lipid hydroperoxide were developed. Based on comparisons of these indices during oxidative stress in typical pathological conditions, such as diabetes and liver damage by toxicants, ASC concentration was found to be the most sensitive index in animal tissues. Antioxidative effect of food factors in vivo can be evaluated on the basis of these indices. Analysis of oxidation of low-density lipoprotein (LDL) revealed that degradation and cross-link of apolipoprotein B-100 (apoB) are extremely facile processes. Fragmented and conjugated apoB proteins are present in normal human serum, and tend to increase with age based on immunoblot analysis. Estimation of these products allows us a mechanism-based diagnosis of atherosclerosis. A significant relationship between plasma ASC level and the sum of these apoB products was found. In conclusion, specifically determined ASC concentration sensitively reflects oxidative stress in tissues.

Animals↗

PubMed2004

Bethesda 2001 implementation and reporting rates: 2003 practices of participants in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology.

CONTEXT: The 2001 Bethesda System for the reporting of cervical cytology specimens and the use of new liquid-based and human papillomavirus testing technologies have led to changes in cervical cytology reporting practices. OBJECTIVES: To analyze current laboratory reporting practices using Bethesda 2001 terminology and to compare results with previous survey data from 1996. DESIGN: Questionnaire survey mailed to 1751 laboratories in mid-2003. PARTICIPANTS: Laboratories enrolled in the College of American Pathologists Interlaboratory Comparison Program in Cervicovaginal Cytology. RESULTS: Of the 759 responding laboratories, most (85.5%) had implemented Bethesda 2001 terminology, and the majority had adopted major changes, such as elimination of the benign cellular changes category and the satisfactory but limited category. The median reporting rate for low-grade squamous intraepithelial lesion was 2.1%, compared to a 1996 median rate of 1.6%, but the increase was confined to liquid-based preparations. Reporting rates for high-grade squamous intraepithelial lesion (median, 0.5%) and atypical squamous cells (ASC) had changed little. Most ASC cases were subclassified as "undetermined significance" (median, 3.9%) with ASC, cannot exclude high-grade SIL accounting for a minority (median, 0.2%). The median ratio of ASC to squamous intraepithelial lesions and carcinomas (SIL+) was 1.4 and was lower than the 1996 median ratio of 2.0. Median reporting rates for squamous abnormalities for 2002 were noted to be significantly higher for liquid-based preparations than for conventional smears, while median ASC/SIL+ ratios were lower. Most laboratories offer human papillomavirus testing, but almost half (47%) of laboratories do not know the percentage of positive testing results in patients with ASC. CONCLUSIONS: Most laboratories have implemented Bethesda 2001 terminology. New criteria and liquid-based methods have led to an increase in low-grade squamous intraepithelial lesion reporting rates and a decrease in ASC/ SIL+ ratios when compared with 1996 data. Liquid-based preparations have higher median squamous intraepithelial lesion rates and lower ASC/SIL+ ratios than conventional smears.

Cervix Uteri↗

PubMedDate not supplied

[Lactose malabsorption diagnosis with H2 breath test].

One hundred and five healthy subjects under investigation for lactose malabsorption were enrolled in this prospective study. After an overnight fast, breath was collected immediately before and every 15 minutes for three hours after an oral administration of 50 g lactose dissolved in 200 mL of water (lactose overload). Blood samples were also collected before and 20, 40 and 60 minutes after the lactose overload for blood glucose determination. Expired H2 was measured by gas chromatography using a Quintron Microlyser and the maximum increase in H2 (delta-H2) was calculated. The area under the curve (ASC-H2) was also calculated using the trapezoid model. Lactose malabsorption was defined as a maximum increase in blood glucose (delta-G) under 18 mg%. The sensibility (S), specificity (E) and accuracy (A) of the H2 determination was analyzed using (a) linear regression [log (ASC-H2) = 4.034-0.029. delta-G], (b) receiver operating curve (ROC) and by (c) Q-Q plot of the cubit root transformation of the ASC-H2 values. Our results demonstrate that ASC-H2, but not delta-H2, correlates with delta-G, suggesting that the measurement of maximum increase in H2 expired following a lactose overload is not reliable for the diagnosis of lactose malabsorption. The cutoff value for the ASC-H2 using linear regression was 3260 (S = 89.3%, E = 80% and A = 86.7%), while using ROC it was 3353 (S = 88.0%, E = 80.0% and A = 85.7%) and while using Q-Q plot method it was 2936 (S = 92.0%, E = 80.0% and A = 88.6%). When the cutoff value was set to 3000, the sensibility, specificity and accuracy were 90.7%, 80.0% and 88.6%, respectively. We conclude that the calculation of the ASC-H2, but not delta-H2, following a lactose overload is reliable in detecting lactose malabsorption and can be used in the clinical practice.

Blood Glucose↗

PubMedDate not supplied

Anti-metastatic effect of an autooxidation-resistant and lipophilic ascorbic acid derivative through inhibition of tumor invasion.

The invasion of human fibrosarcoma HT-1080 cells through Matrigel was shown to be inhibited by pretreatment with ascorbic acid (Asc) or its four derivatives, such as Asc-6-O-palmitate (Asc6Plm), Asc-2-O-phosphate (Asc2P), Asc-2-O-phosphate-6-O-palmitate (Asc2P6Plm), and Asc-5,6-benzylidene (Asc5,6Bz) of non-cytotoxic concentrations for 1 or 18 hr. Two lipophilic derivatives such as Asc6Plm and Asc2P6Plm exerted an invasiveness-inhibitory activity more markedly with 1-hr pretreatment, being a more practical index in terms of the plasma half-life, than Asc, Asc5,6Bz or Asc2P being less lipophilic. Considerably less cytotoxicity (a > 3.3-fold higher IC50 for 1-hr pretreatment) of Asc2P6Plm sufficiently compensated a slightly lower invasiveness-inhibitory activity (a < 1.8-fold higher EC50) as compared with Asc6Plm. Pulmonary metastasis of mouse melanoma B16BL6 cells injected into the tail vein was also inhibited by intravenous administration with Asc2P6Plm dose-dependently. Thus Asc2P6Plm, a lipophilicity-hydrophilicity balanced molecule protectively blockd in the autooxidation-prone moiety, is anticipated as a potent anti-metastatic agent via inhibition of tumor invasion.

Animals↗

PubMed2001

[Vitamin C and uric acid concentrations in plasma and gastric mucosa in patients regularly consuming vegetables, fruits and fruit juices].

UNLABELLED: Vitamin C (Asc) as a reactive oxygen species scavenger inhibits detrimental oxidation reactions and counteracts formation of mutagenic compounds which damage DNA in the gastric and duodenal mucosa. It has been considered as an important factor in reducing risk of gastric carcinoma. However, the role of uric acid (UA) as an antioxidant factor and its influence on gastric mucosa has not been so well investigated. The aim of the study was to evaluate the relationship between vegetable, fruit and fruit juices intake and water soluble antioxidant (Asc and UA) concentrations in plasma and gastric mucosa. The study also assessed the prevalence and intensity of inflammatory changes in mucosa and Helicobacter pylori infection. 34 patients participated in the study. Asc and UA concentrations in plasma and gastric mucosa samples were examined with the use of liquid chromatography (HPLC) method. Histopathological examinations of gastric mucosa were also performed. Higher concentrations of Asc and UA in plasma and less frequent inflammatory changes of gastric mucosa were found in patients regularly consuming vegetables and fruits. It may suggest the protective effect of these compounds on mucosa. No significant relationship was found between H. pylori infection and antioxidant concentrations in plasma and gastric tissue in patients with chronic gastritis. CONCLUSIONS: Diet rich in fruits, vegetables and fruit juices helps in reducing prevalence of inflammatory changes in gastric mucosa. It can be associated with higher Asc and UA concentrations in plasma and higher UA concentrations in gastric mucosa. Lower Asc and UA concentrations in patients with gastritis have no significant relationship with H. pylori infection.

Adult↗

PubMed1999

[Establishment of a method for classification of HBV genome and it's application].

OBJECTIVE: By using the techniques of PCR and restriction fragment length polymorphism (RFLP), we established a classification method for HBV genome based on viral S gene of asymptomatic HBV carriers (AsC). METHODS: By using this method we classified HBV DNA of AsC living in Guangzhou, Shenyang, Beijing and Chongqing. RESULTS: Among the AsC of Guangzhou, genotype B was 32.8%, genotype C 42.7%, mixed genotypes B and C 23.0%, others 1.6%; among the AsC of Chongqing, genotype B was 35.0%, genotype C 40.0%, mixed genotypes B and C 25.0%; among the AsC of Beijing, genotype B was 25.0%, genotype C 50.0%, mixed genotypes B and C 25.0%; among the AsC of Shenyang, genotype B was 11.1%, genotype C 88.9%. The prevalent HBV strains in China are genotype C and genotype B, and genotype C is the main genotype in west China. CONCLUSION: The established method for genotyping is simple and convenient. Using this method, we also classified HBV DNA of the patients with chronic hepatitis B and liver cirrhosis living in Guangzhou, and found that mixed genotypes B and C was in 50.0% of the patients detected, suggesting the mixed infection might lead to a severe damage of the liver tissue.

Carrier State↗

PubMed2003

Repressions of actin assembly and RhoA localization are involved in inhibition of tumor cell motility by lipophilic ascorbyl phosphate.

Our previous study showed that tumor invasion of human fibrosarcoma cells HT-1080 is hardly inhibited by ascorbic acid itself (Asc), but inhibited by 2-O-phosphorylated Asc-6-O-palmitylester (Asc2P6Plm) more markedly than 2-O-phosphorylated Asc or Asc-6-O-palmitylester, and that the inhibitory effect may be attributed to an increase in intracellular Asc derived from Asc2P6Plm. In the present study, the mechanism underlying the inhibitory effect of Asc2P6Plm on tumor invasion was analyzed. Migratory ability of the tumor cells was shown to be inhibited in a dose-dependent manner by either treatment with Asc2P6Plm at 50-300 micro M for 1 h or at 10-50 micro M for 18 h as assessed by cell sheet scratching assay. Hydroxyl radicals in homogenates of Asc2P6Plm-treated HT-1080 cells were markedly diminished relative to those of non-treated cells as evaluated by electron spin resonance method using the spin trapping agent DMPO. This may be closely related to attenuation of intracellular gross reactive oxygen species by Asc2P6Plm as was shown with the redox indicator CDCFH-DA. Actin was localized in the vicinity of the cell membrane abundantly in non-treated cells, but was diminished in a time-dependent manner in Asc2P6Plm-treated cells together with disappearance of pseudopods as shown with the actin-directed agent NBD-phallacidin and by immunocytochemical stain. The cell adhesion-controling molecule RhoA was increased time-dependently in the cytoplasm of Asc2P6Plm-treated cells as shown by Western blots. Thus the inhibition of tumor invasion by Asc2P6Plm was shown to be attributed to decrease in both the cell migratory ability and the actin localization near the cell membrane, which may result from an increase in cytoplasmic RhoA and reduction of intracellular ROS that is achieved by enrichment of intracellular Asc derived from Asc2P6Plm.

Actins↗

PubMed2004

[A 16-year clinical observation on 217 chronic HBsAg carriers].

OBJECTIVE: By means of observing the clinical development of asymptomatic chronic HBsAg carriers (AsC) to explore the clinical rule of development of chronic hepatitis B (CHB) to liver cirrhosis (LC) to hepatocellular carcinoma (HCC) and to seek effective method for blocking the procedure. METHODS: AsCs were selected from health examination according to the diagnostic standard from the National Program for Prevention and Treatment of Viral Hepatitis, by periodical or non-periodical conventional examination of liver diseases, mixed infection of HCV was excluded. A 16-year systematic observation on clinical process of HBV infection series was completed. RESULTS: In the 217 AsCs observed, 21 cases (9.68%) with the HBsAg negatively converted, the average year negative conversion rate being 0.58%, among them, 13/21 cases (61.9%) had production of anti-HBs antigen; 20 cases were clinically cured; 1 case transferred to HCC; 124 cases (57.14%) remained asymptomatic carriers; 73 transferred to chronic liver disease, showing a tendency of gradually developing from CHB to LC to HCC, the year transferring rate from AsC to LC and HCC being 1.04% and 0.40%, respectively. Fifteen patients died of liver diseases, in which one died of severe CHB, 3 of LC and 11 of HCC. CONCLUSION: Different clinical end-results may reveal in AsCs according to their age and regulation on immune response to HBV. Few of the HCC and LC patients were HBeAg (e+) positive, they often reveal HBeAg (e-) negative or anti-HBe positive. HCC always develops on the basis of liver fibrosis or cirrhosis, which are the prophase of HCC, and patients with liver fibrosis or cirrhosis are the high risk group of developing HCC. HCC is not only the terminal pathologic stage of hepatopathy, but also one of the most important factors that causes death of chronic hepatopathy. From the viewpoint of integrative medicine in typing hepatopathy to observe the clinical speciality of AsC developing to CHB, LC and HCC, it is considered that the degree of blood stasis is in accordance with the development of hepatopathy.

Carcinoma, Hepatocellular↗

PubMed2005

[Adenovirus mediated antisense c-myc gene on the chemotherapy sensitivity of osteosarcoma cells to cisplatin].

OBJECTIVE: To construct the recombinant adenovirus encoding antisense c-myc fragment and to investigate its effect on the chemotherapy sensitivity of osteosarcoma MG-63 cells to cisplatin. METHODS: The recombinant adenovirus (Ad-Asc-myc) encoding antisense c-myc fragment was constructed by cloning c-myc cDNA of about 720 base pairs in a reverse direction into adenovirus vector, then undergoing recombination, amplifying and being complemented in vivo. The osteosarcoma MG-63 cells were transfected by the Ad-Asc-myc in vitro, and Wright staining, Acridine Orange staining, Western Blot, MTT, Flow Cytometry (FCM) were used to study cell morphology, expression of c-myc protein, tumor cell proliferation in vitro, apoptosis and cell cycle change. RESULTS: Ad-Asc-myc encoding antisense c-myc fragment was obtained with the titer of 2 x 10(9) pfu/ml. Ad-Asc-myc down-regulated the expression of c-myc protein after transfected MG-63 cells for 48 h, combined with the treatment of 2.0, 5.0 microg/ml cisplatin for 2 h could inhibit tumor cells proliferation in vitro by 33.4% and 54.2% respectively, which were significantly difference compared with control recombinant adenovirus (Ad-LacZ) groups (P < 0.05). Acridine Orange staining and FCM analysis showed that Ad-Asc-myc could induce apoptosis of transfected cells, which was enhanced by the treatment of cisplatin cell. Cycle analysis showed that obvious G2/M phase arrested in transfected cells. CONCLUSION: Ad-Asc-myc increases the chemotherapy sensitivity of osteosarcoma MG-63 cells to cisplatin as well as induced apoptosis.

Adenoviruses, Human↗

PubMed2005

Cervical cytological screening and management in pregnant and postpartum women.

OBJECTIVE: To examine and follow up cervical cytology of pregnant and postpartum women and study their cytopathologic characteristics, so as to determine screening and managing programs for abnormal cervical cytology. METHODS: Totally 5296 patients in pregnancy and postpartum, in which 3729 by computer-assisted cytology test and 1567 by liquid-based monolayers cytology test, were examined and diagnosed by the Bethesda System made in 2001. Those proven epithelial abnormalities patients were followed up until the lesions regressed to normal. The remaining patients, who exhibited persistent abnormalities or progression, were given further examinations. RESULTS: The positive rate of cervical cytological test was 8.72% (462/5296), including squamous carcinoma (SCA) 1 case (0.02%), high grade squamous intraepithelial lesion (HSIL) 34 cases (0.64%), low grade squamous intraepithelial lesion (LSIL) 145 cases (2.74%), atypical glandular cells (AGC) 5 cases (0.09%), atypical squamous cells cannot exclude HSIL (ASC-H) 14 cases (0.26%), atypical squamous cells of undetermined significance (ASC-US) 263 cases (4.97%). The 419 proven cytological abnormality cases were followed up successfully. The total transnegative rate in three months was 73.74% (309/419), in which 303 cases (72.32%) persisted normal status for more than six months after regression. And the transnegative rate of ASC-US, ASC-H, AGC, LSIL, and HSIL were 79.56%, 64.29%, 100%, 72.14% and 44.12%, respectively. Forty-six cases received biopsy directed by colposcopy. The distribution of coincidence of cytopathologic and histopathologic diagnosis was: SCA 1 case (100%), HSIL 10 cases (76.92%), LSIL 13 cases (65%), ASC-H 2 cases (50%), ASC-US 3 cases (37.50%), total 29 cases (63.04%). CONCLUSIONS: We should cast more attention to screening cervix lesions in pregnant and postpartum women. Their cytopathologic characteristics are liable to make the clinician give a false positive diagnosis. So we propose to follow up them closely and to lower the indication of biopsy.

Adult↗

PubMed2006

[Influence of gastric juice pH on the metabolism of vitamin C in gastric mucosa and juice].

UNLABELLED: Vitamin C is present as ascorbic acid (Asc) with antioxidative properties and as its oxidation product dehydroascorbic acid (dAsc). Asc is actively transported from blood to gastric juice where it prevents formation of carcinogenic nitrosamines and protects mucosa from reactive oxygen species. Another important function of gastric mucosa is proton pump-dependent secretion of hydrochloric acid. The pump maintains high pH gradient between gastric juice and plasma. The aim of the work was to analyse relations between gastric juice pH and concentrations of Asc and dAsc in plasma, gastric mucosa and juice as well as other factors modifying metabolism of vitamin C and function of gastric mucosa. MATERIALS AND METHODS: 31 patients were subjected to diagnostic endoscopy due to dyspepsia. Concentrations of Asc and dAsc were measured in plasma, gastric mucosa and juice with HPLC method. pH of gastric juice was determined. Histopathology examination of mucosa and urease test for Helicobacter pylori were performed. Data concerning dyspeptic symptoms and used drugs, including vitamin C preparations, were collected. RESULTS: Patients taking vitamin C preparations had significantly lower gastric juice pH values than the others (median 2.2 vs 5.4; p < 0.01). Treatment with vitamin C preparations was also associated with higher Asc concentrations in gastric juice (median 16.6 vs. 1.8 micromol/L; p < 0.09); the difference was statistically significant in the subgroup of patients with gastritis (median 16.6 vs. 0.1 micromol/L; p < 0.04). Strong negative correlations of pH with Asc (Rs = -0.67; p < 0.001) and dAsc (Rs = -0.48; p < 0.01) concentrations were observed in gastric juice. Positive correlation of pH and relative dAsc content expressed as percent of total vitamin C concentration in gastric juice was also statistically significant (Rs = +0.48; p < 0.05). CONCLUSIONS: Performance of the proton pump and vitamin C metabolism in the stomach are closely mutually connected. Modification of hydrochloric acid secretion may affect gastric juice vitamin C concentration. Potentially disadvantageous influence of antisecretory drugs on the mechanisms of antioxidative protection in the stomach needs further investigation.

Ascorbic Acid↗

PubMed2006

[Use of high-risk human papillomavirus DNA testing to deal with atypical squamous cells undetermined significance and low squamous intraepithelial lesion].

OBJECTIVE: To explore the role of high-risk human papillomavirus (HPV) DNA testing in improvement of recognition of cervical intraepithelial lesions (CIN) 2, 3 or cervical cancer confirmed by biopsy in women with abnormal cervical cytology including atypical squamous cells undetermined significance (ASC-US) and low squamous intraepithelial lesion (LSIL). METHODS: Total 940 patients with abnormal cervical liquid-based cytology including ASC-US and LSIL were included in this study. Hybrid capture II assay was applied in the high-risk HPV detection. The cervical pathologic diagnoses were obtained under colposcopy guided biopsy. RESULTS: Of the 940 cases, 497 were ASC-US, and 443 LSIL. With pathological diagnosis of cervical biopsy, 417 cases were chronic inflammation, 315 condyloma, 124 CIN 1, 65 CIN 2, 19 CIN 3 or cervical cancer. The positive rate of high-risk HPV DNA in groups of ASC-US and LSIL were 59.6% and 84.9%, respectively. In each group of abnormal cytology, detection rates of CIN 2, 3 or cervical cancer in patients with positive HPV DNA were 8.8% and 14.1%, respectively, which were higher than those with negative HPV DNA (0.2% and 6.0%, P < 0.05). In group of ASC-US, high-risk HPV DNA test had a negative predictive value of 99.5%; detection rates of CIN 2, 3 or cervical cancer in patients with HPV DNA virus load 1-9.99 and > or = 10 was 1.6% and 10.7%, respectively. CONCLUSION: High-risk HPV DNA test were helpful to improve the detection rates of CIN 2, 3 or cervical cancer in patients with ASC-US.

Carcinoma, Squamous Cell↗

PubMed1989

[Circulating mature NK (Leu11+) cells positive for IL2 receptor and HLA-DR in patients with various liver diseases and asymptomatic HBsAg carriers].

IL2R+ Leu11+ cells (A) and HLADR+ Leu11+ cells (B) of peripheral blood in patients with various liver diseases and ASCs were measured using double colour immunofluorescence assay of MoAb with FACS flow cytometry. 1) The mean % of IL2R+ Leu11+ cells which was 0.5 +/- 0.2 in healthy controls, decreased significantly in HCC in comparison with CALD, ASC and healthy controls, and in ASC rather than in healthy controls. They (A) were less than 0.1% in eight of thirteen cases with HCC, in one of twenty cases with CALD and of eleven ASCs, respectively. 2) In the mean % of HLADR+ Leu11+ cells which was 2.9 +/- 1.8 in healthy controls there was not a significant difference among HCC, CALD, ASC, AH and healthy controls. They (B) were less than 0.1% only in one case with HCC. 3) The value of fluorescence intensity of IL2R on IL2R+ Leu11+ cells reduced in B-CALD, ASC, AH and HCC, and one of HLADR on HLADR+ Leu11+ cells increased in CALD. These results suggested that the decrease of IL2R+ Leu11+ cells was due to the existence of HCC.

Antigens, Differentiation↗

PubMed1988

The otolithic origin of the vertical vestibuloocular reflex following bilateral blockage of the vertical semicircular canals in the rabbit.

The influence of bilateral plugs of the anterior and posterior semicircular canals (ASCs, PSCs) on the vertical vestibuloocular reflex (VVOR-0) of the rabbit, oscillated about the longitudinal axis maintained in a horizontal orientation, was studied. Bilateral plugs of either the ASCs or PSCs reduced the gain of the VVOR-0 evoked by stimulus frequencies above 0.005 Hz, but left a residual gain of the VVOR at higher stimulus frequencies that could be attributed to the remaining vertical canals and utricular otoliths. Bilateral plugs of both the ASCs and PSCs totally eliminated the canal component of the VVOR-0, as determined from measurements made when the animal was oriented at 90 degrees ("nose up") with respect to the earth horizontal axis, eliminating changes in the gravitational vector acting on the utricular maculae (VVOR-90). Bilateral plugs of both the ASCs and PSCs also eliminated the nonlinear increase in gain observed at intermediate frequencies in intact rabbits when oscillated about a supine orientation (VVOR-180). The contribution of the utricular otolith to the VVOR-0 in rabbits with both the ASCs and PSCs plugged was compared with the predicted otolith contribution based on the assumption of linear summation of semicircular canal and utricular signals. The assumption of linear summation appears to be incorrect. Bilateral plugs of the ASCs and PSCs increased the latency and the time constant of vertical eye movements evoked by step-roll stimulation about the longitudinal axis maintained in a horizontal orientation.

Animals↗

PubMed1981

The primary immune response of brown trout (Salmo trutta) to cellular and soluble antigens: Enumeration of antibody-secreting and antigen-binding cells, and the production of antibody.

Significantly increased numbers (P less than 0.01) of antigen-binding (ABC) and antibody-secreting cells (ASC) were stimulated, in the spleen and the anterior kidney (AK) of the brown trout (Salmo trutta), by a single intraperitoneal injection of Salmonella typhimurium lipopolysaccharide (LPS), keyhole limpet haemocyanin (KLH), sheep red blood cells (SRBC) or KLH- or LPS-coated SRBC. With the exception of the SRBC group, the spleens contained more AVC and ASC per 10(6) lymphoid cells than the AK. Fewer ASC were found when guinea pig complement was used than with salmon serum; with 3 exceptions the differences were significant. In both organs, ABC and ASC were detected between 2 and 4 days after injection and maxima were reached between day 14 and day 18 in most of the experimental groups. However, with fish immunised with SRBC, ABC and ASC first occurred on day 6 and peak counts were obtained on day 12. In all groups the counts had returned to background levels by day 28. The coupling of LPS or KLH tro SRBC, with one exception, significantly increased the numbers of ABC and ASC (p less than 0.02) compared to when uncoated SRBC, LPS or KLH were injected. There was no significant change when the ABC results for antigen-coated SRBC were compared to those obtained when LPS was injected by itself. Following antigenic stimulation there were significant increases (p less than 0.05) in most cases in both the spleen and the AK to body weight ratios. There were significant differences in both the spleen and the AK to bodyweight ratios. There were significant differences (p less than 0.001) between KLH and KLH-SRBC (spleen and AK), LPS and LPS-SRBC (spleen and AK) and SRBC and LPS-SRBC (AK alone). Antibodies were detected 2 to 8 days after sensitised cells were first found and reached maxima 5 to 16 days after the cellular responses. The titres obtained with experimental sera were significantly different (p less than 0.001) compared to the appropriate control groups.

Animals↗

PubMed1996

Inhibition of hepatocellular carcinoma development and erythrocyte polyamine levels in ODS rats fed on 3'-methyl-4-dimethylaminoazobenzene by hemicalcium ascorbate, 2-O-octadecylascorbic acid, and ascorbyl palmitate.

We examined the modifying effect of hemicalcium ascorbate (Ca-Asc), and its lipophilic derivatives, 2-O-octadecylascorbic acid (CV-3611) and ascorbyl palmitate (AscP), on hepatocarcinogenesis by 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) in ODS rats (a mutant unable to synthesize ascorbic acid). Male 14-week-old ODS rats were given a modified AIN-A diet or the diet containing 0.06% 3'-Me-DAB, and drinking water containing 0.1% ascorbic acid. Rats were divided into the following eight groups: Group 1, no treatment (basal diet alone); Group 2, Ca-Asc; Group 3, CV-3611; Group 4, AscP;Group 5, 3'-Me-DAB; Group 6, 3'-Me-DAB + Ca-Asc; Group 7, 3'-Me-DAB + CV-3611; and Group 8, 3'-Me-DAB + AscP. Ca-Asc (2 g/kg), CV-3611 (0.2 g/kg), and AscP (0.6 g/kg) was administered once every day by gavage. 3'-Me-DAB was given in the basal diet. After 17 weeks, animals were killed by exsanguination, and the liver was weighed and processed for histological examination. Treatment by CV-3611 exerted a marked inhibitory effect on the development of 3'-Me-DAB-induced hepatocellular carcinomas (HCC) as measured by multiplicity. Although less effective than CV-3611, Ca-Asc and AscP also showed inhibitory effect. We have also studied the correlation of erythrocyte (RBC) polyamine levels and HCC development. RBC polyamine levels were inhibited by Ca-Asc and its derivatives, indicating it may be a marker of hepatocarcinogenesis.

Animals↗

PubMed1996

Change in ascorbate radical production in an irradiated experimental tumor with increased tumor size.

We have reported that ascorbate radical (Asc.-) could serve as an indicator of the amount of hydroxyl radical and superoxide produced by irradiation in vivo. Using this method, we investigated the relationship between tumor size and Asc.- production after irradiation (10 Gy) and between tumor size and the radical-scavenging ability of WR-2721 (300 mg/kg). Asc.- was measured in normal muscle and SCC-VII tumors transplanted into mice (n = 6). In tumors, the increase in Asc.- significantly decreased with increasing tumor size (r = -0.483; P < 0.05). The increase in Asc.- production after irradiation was more inhibited by WR-2721 in normal muscle tissue than in tumor tissue at various sizes. In tumors, the increase in Asc.- was less inhibited by WR-2721 with increasing tumor size. These results demonstrate that the increase in radical production after irradiation and drug distribution decreased with increasing tumor size and that WR-2721 has excellent differential protection. This method is expected to measure changes in the amounts of local hydroxyl radical and superoxide modified by a change of tumor environment or drug administration.

Amifostine↗