1. The hepatoprotective activity of an aqueous-methanolic extract of Fumaria parviflora was investigated against paracetamol- and CCI4-induced hepatic damage. 2. Paracetamol (1 g/kg; orally) produced 100% mortality in mice; pretreatment of animals with the plant extract (500 mg/kg; orally) reduced the death rate to 50%. 3. Pretreatment of rats with plant extract (500 mg/kg, orally twice daily for 2 days) prevented (P < 0.001) the paracetamol (640 mg/kg)-induced rise in serum enzymes alkaline phosphatase (ALP) and transaminases (GOT and GPT), whereas the same dose of the extract was unable to prevent (P>> 0.05) the CCI4-induced rise in serum enzyme levels. 4. Posttreatment with 3 successive doses of the extract (500 mg/kg, 6 hourly) also restricted the paracetamol-induced hepatic damage. 5. The plant extract (500 mg/kg; orally) caused significant prolongation in pentobarbital (75 mg/ kg)-induced sleep as well as increased strychnine-induced lethality in mice (P < 0.05), suggestive of an inhibitory effect on microsomal drug metabolizing enzymes (MDME). 6. It is conceivable therefore, that Fumaria parviflora extract exhibits a selective protective effect against paracetamol-induced hepatotoxicity, probably mediated through MDME inhibition.

1. The hepatoprotective activity of aqueous-methanolic extract of Cyperus scariosus (Cyperaceae) was investigated against acetaminophen and CCl4-induced hepatic damage. 2. Acetaminophen produced 100% mortality at a dose of 1 g/kg in mice while pretreatment of animals with plant extract (500 mg/kg) reduced the death rate to 30%. 3. Acetaminophen at a dose of 640 mg/kg produced liver damage in rats as manifested by the rise in serum levels of alkaline phosphatase (ALP), glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) to 430 +/- 68, 867 +/- 305 and 732 +/- 212 IU/l (n = 10) respectively, compared to respective control values of 202 +/- 36, 59 +/- 14 and 38 +/- 7. 4. Pretreatment of rats with plant extract (500 mg/kg) significantly lowered (P < 0.05) the respective serum ALP; GOT and GPT levels to 192 +/- 31, 63 +/- 9 and 35 +/- 8. 5. The hepatotoxic dose of CCl4 (1.5 ml/kg; orally) raised serum ALP, GOT and GPT levels to 328 +/- 30, 493 +/- 102 and 357 +/- 109 IU/l (n = 10) respectively, compared to respective control values of 177 +/- 21, 106 +/- 15 and 47 +/- 12. 6. The same dose of plant extract (500 mg/kg) was able to significantly prevent (P < 0.05) CCl4-induced rise in serum enzymes and the estimated values of ALP, GOT and GPT were 220 +/- 30, 207 +/- 95 and 75 +/- 38, respectively. 7. The plant extract also prevented CCl4-induced prolongation in pentobarbital sleeping time confirming hepatoprotectivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Ochratoxin A (OTA) is a carcinogen targeting proximal tubules at the renal outer medulla (ROM) in rodents. We previously reported that OTA increased mutant frequencies of the red/gam gene (Spi(-)), primarily deletion mutations. In the present study, Spi(-) assays and mutation spectrum analyses in the Spi(-) mutants were performed using additional samples collected in our previous study. Spi(-) assay results were similar to those in our previous study, revealing large (>1kb) deletion mutations in the red/gam gene. To clarify the molecular progression from DNA damage to gene mutations, in vivo comet assays and analysis of DNA damage/repair-related mRNA and/or protein expression was performed using the ROM of gpt delta rats treated with OTA at 70, 210 or 630 µg/kg/day by gavage for 4 weeks. Western blotting and immunohistochemical staining demonstrated that OTA increased γ-H2AX expression specifically at the carcinogenic target site. In view of the results of comet assays, we suspected that OTA was capable of inducing double-strand breaks (DSBs) at the target sites. mRNA and/or protein expression levels of homologous recombination (HR) repair-related genes (Rad51, Rad18 and Brip1), but not nonhomologous end joining-related genes, were increased in response to OTA in a dose-dependent manner. Moreover, dramatic increases in the expression of genes involved in G2/M arrest (Chek1 and Wee1) and S/G2 phase (Ccna2 and Cdk1) were observed, suggesting that DSBs induced by OTA were repaired predominantly by HR repair, possibly due to OTA-specific cell cycle regulation, consequently producing large deletion mutations at the carcinogenic target site.

The elevated serum glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) rate among people with intellectual disabilities (ID) is unknown and have not been sufficiently studies. The present paper aims to provide the profile of GOT and GPT, and their associated relationship with other biochemical levels of children or adolescents with ID. A cross-sectional design was conducted in three Taiwanese public special schools to analyze annual health examination chart of students with ID. There were 1041 aged 3-21 years children and adolescents with ID participated in the study. The results show elevated rate of GOT and GPT were 3.7% and 7.2%, the study indicates the elevated GPT in children and adolescents with ID is higher than the general school aged children in Taiwan. In multiple linear regression models show that the factors of BMI, HBsAg, TC and UA can significantly explain the GOT value (R(2)=0.275). Those factors of gender, BMI, HBsAg, TC and UA can significantly explain 44.4% variation of GPT value (R(2)=0.444). To prevent the further liver disease burden in people with ID, the study highlights that the health care professionals should assess liver functions of this group of people, and to inform their caregivers the importance of implement regular liver health check-up.

Dimethylformaide (DMF) is a major solvent predominately used in synthetic leather and resin production. Many human and animal studies have linked the cause of hepatoxicity to DMF. Previously, the authors demonstrated the significant dose-response relationship between abnormal liver function tests and DMF exposure and the interaction with hepatitis B virus (HBV) infection in Taiwanese workers. Because the toxic effect of various chemicals can be modified by metabolic traits, the study also investigated the influence of the glutathione S-transferases (GSTM1 and GSTT1) on the toxic effect of DMF. The average DMF exposure concentration was 23.87 ppm (range 5.2-86.6 ppm) in the high-exposure >>/=5 ppm) group and 2.41 ppm (range 0.9-4.3 ppm) in the low-exposure (<5 ppm) group. There were 13 of 44 (29.6%) abnormal liver function tests (elevations of either glutamate oxaloacetate transaminase (GOT) or glutamate pyruvate transaminase (GPT)) among the high DMF exposure workers, two of 22 (9.1%) abnormal liver function tests among the low DMF exposure workers. Chronic liver disease as determined by ultrasonography was present in seven of 44 (15.9%) high DMF exposure workers, and 0 of 22 (0%) low DMF exposure workers. There were 11 of 34 (32.4%) abnormal liver function tests among the GSTT1 null genotype workers, and four of 32 (12.5%) abnormal liver function tests among the GSTT1-positive genotype workers. Compared with the low DMF exposure workers, the adjusted odds ratio and 95% confidence intervals for abnormal liver function tests was 6.78 (0.94-48.7) for the high DMF exposure workers. Compared with the GSTT1-positive genotype workers, the adjusted odds ratio and 95% confidence intervals for abnormal liver function tests was 4.41 (1.15-16.9) for the GSTT1 null genotype workers. Compared with the low DMF group with GSTT1-positive genotype workers, the odds ratio (adjusted for HBV status) of abnormal liver function test was 12.38, 95% CI=(1.04-146.9) for the high DMF group with GSTT1 null genotype workers. This study indicates that abnormal liver function and chronic liver disease are associated with DMF exposure, and there are more than multiplicative interaction effects on abnormal liver function tests between the DMF exposure and the GSTT1 genotype.

OBJECTIVE

Impaired Theory of Mind (ToM) is found in adults with schizophrenia and is associated with paranoid symptoms. Insecure attachment is proposed to underlie impaired ToM as well as paranoia. Insight into associations between insecure attachment and impaired ToM skills may help clinicians and patients to understand interpersonal difficulties and use this knowledge to improve recovery. This study used a visual perspective-taking task to investigate whether cognitive ToM is already impaired in adolescents with early psychosis as compared to controls. Also investigated was whether perspective-taking and paranoia are associated with insecure (adult) attachment.

METHODS

Thirty-two adolescent patients with early psychosis and 78 healthy controls participated in this cross-sectional study design and completed the level 1 perspective-taking task, psychopathology assessments (CAPE, PANSS), paranoid thoughts (GPTS), attachment style (PAM) and the WASI vocabulary.

RESULTS

Patients did not significantly differ in level-1 perspective-taking behaviour compared to healthy controls. No significant associations were found between perspective-taking, paranoia and attachment. Insecure attachment was significantly related to paranoid thoughts, after controlling for illness-related symptoms.

CONCLUSIONS

No impairment of level-1 perspective-taking was found in adolescent patients with early psychosis compared to healthy controls. Results indicate that level-1 perspective-taking is not impaired during the early stages of psychotic illness. The association between paranoia and attachment support previous findings and provide further insight into the nature of psychotic symptoms. Understanding the role of attachment in paranoia may help patients and their care workers to gain insight into the reasons for the development or persistence of symptoms. Future research should compare early psychosis samples with more chronic samples to explore whether perspective-taking deteriorates during the course of the illness.

Circulating desialylated glycoprotein level in acute hepatitis was studied by using the competitive binding assay reported by us. Statistically significant differences of the level among acute hepatitis in the peak of illness, fulminating hepatitis and normal subjects were observed. The desialylated glycoprotein level in acute hepatitis was elevated associating with S-GPT and serum bilirubin levels, and it returned to the normal range before S-GPT and serum bilirubin were normalized. The desialylated glycoprotein in a fulminant hepatitis was increasing associated with bilirubin even when S-GPT was decreasing.

The effect of a nucleoside-nucleotide mixture on liver injury of rats induced by D-galactosamine was studied by examining changes in function and histopathology of the liver. Animals with liver damage received total parenteral nutrition with glucose and amino acids supplemented with a nucleoside-nucleotide mixture containing inosine, cytidine, GMP, uridine and thymidine, or with uridine which inhibits galactosamine injury, or with liver cell extract containing flavin adenine dinucleotide and nucleic acid derivatives. As control, animals with liver damage received total parenteral nutrition with glucose and amino acids only. The serum GOT and GPT concentrations were significantly lower in the group supplemented with nucleoside-nucleotide mixture than those in other groups. A large dose (1.2 g/kg) of uridine inhibited liver injury, but a lower dose (0.14 g/kg) did not have any effect, whereas nucleoside-nucleotide mixture containing the same amount of uridine inhibited the injury. Liver cell extract also did not improve liver function. Thus infusion of a physiological and balanced mixture of nucleosides or nucleotides may improve liver function in rats with liver injury.

Alpha and beta interferons control expression of a selectable marker in the human hypoxanthine phosphoribosyltransferase-negative cell line 2fTGH, in which transcription of gpt is regulated by the upstream region of an interferon-responsive human gene. Selection of mutagenized 2fTGH cells in hypoxanthine-aminopterin-thymidine medium yielded mutants in one recessive (C1) and two dominant (C2 and C3) complementation groups. The mutants constitutively expressed low levels of beta interferon (C1), alpha interferon (C2), or both (C3).

The disadvantages of using human cultured cells for biochemical and genetic studies are their limited lifespan in vitro and their lack of chemical selection markers. These problems are now overcome by transfecting human cultured fibroblasts with the pSV3-gpt and pSV3-neo plasmid DNA which carry genes coding for the immortalizing SV40 large T-antigen and dominant selection markers. Transformed human fibroblasts were obtained at a frequency of about 10(-5) with both selection systems. These transformed cells showed a twofold increase in growth rate and three to tenfold increase in cell number at confluence. The improved growth characteristics were associated with the expression of the SV40 T-antigen detected with immunoprecipitation. These cell lines also changed from their usual spindle shapes to an epithelioid morphology characteristic of transformed cells. From 60 to 100% of the cells transfected with pSV3 plasmid DNA demonstrated numerical and structural abnormalities in their karyotypes. Cells transfected with DNA from a similar plasmid, pSV2-neo, which differed from the pSV3-neo plasmid only by missing the sequence encoding the complete early region of SV40, neither expressed T-antigen nor showed any change in morphology, improvement in growth characteristics or abnormalities in karyotype. However, they were still selectable with the aminoglycoside G-418. Therefore, by appropriate choice of vector plasmids, dominant selection markers and improved growth characteristics can be imparted separately or simultaneously to human fibroblasts. The morphological, biochemical and chromosomal changes resulting from such transformations must be recognized in using this approach for biochemical and genetic studies.

A cDNA clone isolated from Chinese hamster ovary cells conferred elevated GlcNAc-1-P-transferase (GPT) activity and resistance to tunicamycin in transfected cells (Zhu, X., and Lehrman, M. A. (1990) J. Biol. Chem. 265, 14250-14255). It had been assumed that this cDNA, termed TRG for tunicamycin resistance gene, encoded GPT enzyme. However, other functions were not ruled out. Thus, by one of several mechanisms, the TRG protein could have instead functioned by activation of the transfected host's endogenous GPT enzyme. To analyze the biochemical function of the TRG protein, hamster TRG cDNA was stably expressed at high levels in Chinese hamster ovary cells. In addition, several antipeptide polyclonal antibodies directed against the predicted TRG protein were obtained. With these tools in hand, experiments were performed to test the hypothesis that the TRG encodes GPT enzyme, as well as to rule out other possible functions for the TRG protein. These experiments included examination of the effects of solubilization of membranes on TRG-dependent GPT activity, the apparent binding of tunicamycin to the TRG protein, and the immunoadsorption of GPT activity with TRG protein-specific antibodies. From these results, we conclude that the hamster TRG most likely encodes GPT enzyme.

We developed a positive selection method for recovering Marek's disease virus (MDV) recombinants. The Escherichia coli xanthine-guanine phosphoribosyltransferase gene (gpt), under the control of the major immediate-early promoter from cytomegalovirus, was inserted into the inverted repeats flanking the unique long (UL) region of a non-pathogenic serotype 2 MDV strain 281MI/1. In a second demonstration of the usefulness of the positive selection system, the gpt gene was inserted into the inverted repeats flanking the unique short (US) region of the turkey herpesvirus (HVT) strain FC126. The targeted insertion site in 281MI/1 was in a previously established nonessential site for virus replication. The targeted insertion site for FC126, at the junction of the UL and US regions, is a nonessential site for in vitro replication of herpes simplex virus. Recombinant viruses were easily selected by incubating the transfected cells in mycophenolic acid (MPA)-containing medium. Purification of recombinants resulted from a series of trypsinization and sonication steps combined with the culturing of virus in MPA-containing medium to inhibit wild-type virus replication. This simple technique for recovering MDV and HVT recombinants should increase the efficiency of identifying nonessential sites and gene function analysis by insertional mutagenesis.

Genes have been cloned from Salmonella typhimurium which when present on the multicopy plasmid pBR322 in the E. coli strain NT31 confer a Gua+ phenotype on this strain. NT31 is a purE gpt double mutant and it was expected that a Gua+ phenotype could be conferred on it by the cloning of either gpt or purE. It was, however found that in addition to these two loci the molecular cloning of another gene, which has been identified as hpt, in pBR322 confers a Gua+ phenotype on NT31. This result is explained by the overproduction of the hpt gene product, hypoxanthine phosphoribosyl transferase, which compensates for the lack of the gpt product guanine-xanthine phosphoribosyl transferase. Restriction analysis of the three loci, gpt, hpt and purE is also presented.

Salmonella typhimurium strain GP660 (proAB-gpt deletion, purE) lacks guanine phosphoribosyltransferase and hence cannot utilize guanine as a purine source and is resistant to inhibition by 8-azaguanine. Strain GP660 was mutagenized and a derivative strain (GP36) was isolated for utilization of guanine and hypoxanthine, but not xanthine, as purine sources. This alteration was designated sug. The strain was then sensitive to inhibition by 8-azaguanine. Column chromatographic analysis revealed the altered phosphoribosyltransferase peaks for both hypoxanthine and guanine to be located together, in the same position as hypoxanthine phosphoribosyltransferase (hpt gene product) of the wild-type strain. Genetic analysis showed the sug mutation to be allelic with hpt. Therefore sug represented a modification of the substrate specificity of the hpt gene product.

1. The present study addresses the possibility of the existence of different kinin B2 receptor subtypes in the guinea-pig by evaluating the affinity of peptide and nonpeptide receptor antagonists. For this purpose, jugular vein rings, ileum segments, lung parenchymal and trachea strips were set up in organ baths for isometric tension measurements. The experiments were conducted in the presence o indomethacin (3 microM), atropine (10 microM) and captopril (10 microM). 2. BK contracted jugular vein (JV), ileum (GPI), parenchyma (LP) and trachea (GPT) with an EC50 of 13.2 +/- 1.4 nM (n=27), 11.2 +/- 2.1 (n=26), 23.6 +/- 6.3 (n=26), and 33.0 +/- 6.5 (n=27), respectively. Thiorphan, a neutral endopeptidase (EC 3.4.34.11) inhibitor and MERGETPA (DL-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid), a carboxypeptidase inhibitor, had no effect on the BK-induced contractions of JV, GPI and LP. In the GPT, thiorpan potentiated the contractile response to BK and was thus added in the corresponding experiments. 3. The peptide B2 receptor antagonist, Hoe 140 and the nonpeptide compound, WIN 64338, behaved as noncompetitive antagonists against contractile responses to cumulative BK in the four tissues although Hoe 140 appeared as a competitive inhibitor in the GPT only. IN order to compare the inhibitory potency of these compounds between tissues, pKB values were determined. Mean values of pKB for Hoe 140 were 8.05 +/- 0.07, 8.43 +/- 0.11, 8.13 +/- 0.18, and 8.52 +/- 0. 25 in the JV, GPI, GPT and LP, respectively. WIN 64338 gave mean pKB values of 6.89 +/- 0.10, 7.57 +/- 0.12, 7.36 +/- 0.12 adn 7.51 +/- 0.28 in the JV, GPI, LP and GPT, respectively. 4. D-Arg [Hyp3, D-Phe7, Leu8]BK and D-Arg[Hyp3, D-Phe7]BK (NPC 567) inhibited in a competitive fashion the concentration-response curves to BK. Values of pA2for each compound were not significantly different in the four tissues and were between 5.81 and 6.31 for D-Arg [Hyp3, D-Phe7, Leu8]BK and between 5.55 and 5.65 for NPC 567.

Metallothionein (MT) is induced in the liver not only by heavy metals, but also by stress such as starvation. However, the meaning of the induced MT during starvation has never been clear. In this study, we investigated the relationship between changes in hepatic MT synthesis and the hepatic damage that occurs during starvation. MT synthesis was assessed by measuring MT contents and the expression of the MT gene in the liver. The hepatic damage was assessed by measuring glutamic pyruvic transaminase (GPT) and glutamic oxaloacetic transaminase (GOT) activities in the serum. MT synthesis in the liver increased over the normal level by starvation, but decreased under the normal level by refeeding after starvation. Both GPT and GOT activities of the refeeding group were higher than those of the control group. However, MT synthesis increased by a subcutaneous injection with CdCl(2) (1 mg Cd /kg) at the same time as refeeding after starvation. At this point, GOT activity decreased until it reached the normal level. MT synthesis decreased by refeeding after starvation, and from the results found in this study, we proposed the hypothesis that the liver damage caused by refeeding after starvation might be due to the decrease in the synthesis of a sufficient amount of MT induced by metals.

OBJECTIVE

We wished to determine the relation between liver function, beta-, and omega-, and omega-1-oxidation metabolites and 4-en-valproate (VPA).

METHODS

We measured the serum levels of VPA and its metabolites in children and adolescent receiving high-dose VPA plus phenytoin (PHT) therapy using gas chromatography-mass spectrometry with selected ion monitoring (GC/MS/ SIM).

RESULTS

In high-dose VPA plus PHT polytherapy, the total VPA serum concentration was distinctly low, the concentrations of total beta-oxidation metabolites were decreased, the percentage values of VPA (percent of VPA) of total beta-oxidation metabolites were increased, and the E-2-en-VPA/3-keto-VPA ratios were decreased, as compared with those in high-dose VPA monotherapy. In high-dose VPA plus PHT polytherapy, 4-en-VPA (microM) was decreased and the concentrations of [omega + (omega-1)]-oxidation metabolites (microM) were decreased as compared with those in high-dose VPA monotherapy. In high-dose VPA plus PHT, serum glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT) and lactic dehydrogenase (LDH) did not correlate significantly with the ¿beta/omega + (omega-1)¿ metabolites ratio and 4-en-VPA levels, but serum GOT, GPT, and LDH were increased as compared with those in high-dose VPA therapy. We were not able to establish a significant relation between the formation of metabolites of VPA metabolites and liver dysfunction in patients receiving high-dose VPA and PHT concurrently.

CONCLUSIONS

Metabolic levels do not appear to be a reliable predictor of hepatotoxicity in children receiving pharmacological antiepileptic drug (AED) therapy.

BACKGROUND

Gastrointestinal (GI) hormones regulate several GI functions, including the proliferation and repair of normal mucosa, and hormone receptors may therefore be implicated in the growth, invasion, and metastasis of cancers of the GI tract. The aim of this study was to determine the cellular distribution of gastrin in intestinal-type gastric cancers, and to determine its relationship to outcomes after R0 gastrectomy.

METHODS

Eighty-six consecutive patients undergoing R0 gastrectomy for adenocarcinoma were studied. Normal gastric mucosa and tumor were stained for gastrin and their specific cellular distribution was determined.

RESULTS

The duration of survival of patients whose tumors exhibited well-differentiated gastrin-positive tumor (GPT) cells (n = 12) was significantly poorer than that of patients whose tumors were GPT-negative (5-year survival, 30% vs 54%; P = 0.037). Patients with GPT-positive intestinal-type gastric cancer (5 of 47 patients) had the poorest survival of all (median, 14 months; 5-year survival, 0%; P = 0.006). In a multivariate analysis, only lymph node metastases (hazard ratio [HR], 2.13; 95% confidence interval [CI], 1.2 to 3.79; P = 0.01) and the presence of GPT cells (HR, 6.61; 95% CI, 1.74 to 25.09; P = 0.01) were independently and significantly associated with durations of survival in patients with intestinal-type gastric cancer.

CONCLUSIONS

The presence of GPT cells in patients with gastric adenocarcinoma is a significant and independent prognostic indicator.

Heterocyclic amines (HCAs) have been shown to induce tumors in several organs of rodents, but except for MeIQ and PhIP, other HCAs such as MeIQx and IQ consistently failed to induce colon tumors in mice, whereas MeIQ, IQ, and PhIP exerted colon tumorigenicity in rats. Recently, we found that dietary MeIQx induces genotoxicity in the colon as well as the liver of two different types of reporter gene transgenic mice at subcarcinogenic doses such as 300 ppm. However, in the present study, dietary MeIQx did not significantly induce any tumors in C57BL/6J mice or gpt delta mice even when fed at 300 ppm for 78 weeks, suggesting that the treatment of MeIQx alone was not sufficient to promote colon tumors. In order to clarify a possibility whether such HCAs can induce colon tumors, C57BL/6J mice were fed MeIQx, IQ, or PhIP at a dose of 300 ppm for 12 weeks and, thereafter, twice received 1-week treatment with dextran sulfate sodium (DSS), 2 weeks apart. After 20 weeks, colon tumors including adenocarcinomas were found at incidences of 22%, 24%, and 45% in the groups receiving MeIQx, IQ, and PhIP, respectively, which were significantly (p < 0.05 or 0.01) different from the DSS alone value (0%). Thus our results clearly indicate that, in addition to PhIP, MeIQx and IQ can induce colon tumors in mice under an experimental condition promoting colon tumors.

UNASSIGNED

The Collaborative Ocular Melanoma Study (COMS) established modern treatment recommendations for uveal melanoma. We aim to evaluate patterns of care and survival outcomes in the time after COMS.

UNASSIGNED

The retrospective study population includes 2,611 patients in the SEER database treated for uveal melanoma between 2004-2013. Patients stage were T1-4N0M0. Data analyzed included age, clinical stage, tumor size, race, and treatment. Treatments included enucleation (EN) and globe preserving therapy (GPT), which consisted of limited surgical resection or ablation (LSRA), external beam radiation (EBRT), or brachytherapy (BT). Patients treated with radiation may receive radiation therapy alone (RTA) or radiation therapy and supplemental laser therapy (RT+SLT). We evaluated disease specific survival (DSS) and overall survival (OS) using log-rank statistics, and Cox univariate and multivariate analysis.

UNASSIGNED

The median follow-up was 44 months. Treatment strategy was EN in 538 (20.6%) patients, LSRA in 80 (3.1%), EBRT in 609 (23.3%), and BT in 1,384 (53.0%). 1,876 patients received RTA and 117 received RT+SLT. Enucleation was associated with inferior DSS and OS compared to GPT in multivariate analysis (MVA) (p < 0.01). Limited surgical resection or ablation and radiation had similar DSS and OS. Brachytherapy and EBRT had similar DSS and OS. Radiation therapy and supplemental laser therapy was associated with improved DSS compared to RTA in UVA (p = 0.03), but not MVA. The 5-year DSS for enucleation, RTA, and RT+SLT were 66.7%, 87.0%, and 94.7% (p < 0.01), respectively.

UNASSIGNED

Globe preserving treatments such as limited surgery or radiation are commonly utilized alternatives to enucleation, and resulted in favorable survival outcomes. Additional research is required to compare the outcomes of the various globe preserving treatment strategies.

Previous successful transplantations of human tumour cells into athymic nude mice have been described when cells were injected with a reconstituted basement membrane (matrigel). We have compared the development and the histology of tumours following injection with matrigel or with culture medium of a panel of tumour cells exhibiting different degrees of tumorigenicity. Two cell lines (MCF7 and MCF7/6) required matrigel in order to form tumours. When inoculated with matrigel, all the other cell lines tested [MCF7 gpt, MCF7ras, MCF7(AZ), MCF7(AZ)TD5, MDA-MB 231, HT1080] showed increased tumour take and reduced latency period. Human primary tumours (melanoma, breast and colon cancers) were transplanted successfully into nude mice, in the presence of matrigel. Breast primary tumours or cell lines gave rise to poorly differentiated carcinomas. The other tumours presented histopathological patterns typical of differentiated human cancers.

Bass gill microsomal preparations contain a Mg2+-dependent Na+-stimulated ATPase activity in the absence of K+, whose characteristics are compared with those of the (Na+ + K+)-ATPase of the same preparations. The activity at 30 degrees C is 11.3 mumol Pi X mg-1 protein X hr-1 under optimal conditions (5 mM MgATP, 75 mM Na+, 75 mM HEPES, pH 6.0) and exhibits a lower pH optimum than the (Na+ + K+)-ATPase. The Na+ stimulation of ATPase is only 17% inhibited by 10-3M ouabain and completely abolished by 2.5 mM ethacrinic acid which on the contrary cause, respectively, 100% and 34% inhibition of the (Na+ + K+)-ATPase. Both Na+-and (Na+ + K+)-stimulated activities can hydrolyze nucleotides other than ATP in the efficiency order ATP greater than CTP greater than UTP greater than GTP and ATP greater than CTP greater than GPT greater than UTP, respectively. In the presence of 10(-3)M ouabain millimolar concentrations of K+ ion lower the Na+ activation (90% inhibition at 40 mM K+). The Na+-ATPase is less sensitive than (Na+ + K+)-ATPase to the Ca2+ induced inhibition as the former is only 57.5% inhibited by a concentration of 1 X 10(-2)M which completely suppresses the latter. The thermosensitivity follows the order Mg2+--greater than (Na+ + K+)--greater than Na+-ATPase. A similar break of the Arrhenius plot of the three enzymes is found. Only some of these characteristics do coincide with those of a Na+-ATPase described elsewhere. A presumptive physiological role of Na+-ATPase activity in seawater adapted teleost gills is suggested.

The molecular mechanisms of ethyl methanesulfonate-induced reversion in mammalian cells were studied by using as a target a gpt gene that was integrated chromosomally as part of a shuttle vector. Murine cells containing mutant gpt genes with single base changes were mutagenized with ethyl methanesulfonate, and revertant colonies were isolated. Ethyl methanesulfonate failed to increase the frequency of revertants for cell lines with mutant gpt genes carrying GC----AT transitions or AT----TA transversions, whereas it increased the frequency 50-fold to greater than 800-fold for cell lines with mutant gpt genes carrying AT----GC transitions and for one cell line with a GC----CG transversion. The gpt genes of 15 independent revertants derived from the ethyl methanesulfonate-revertible cell lines were recovered and sequenced. All revertants derived from cell lines with AT----GC transitions had mutated back to the wild-type gpt sequence via GC----AT transitions at their original sites of mutation. Five of six revertants derived from the cell line carrying a gpt gene with a GC----CG transversion had mutated via GC----AT transition at the site of the original mutation or at the adjacent base in the same triplet; these changes generated non-wild-type DNA sequences that code for non-wild-type amino acids that are apparently compatible with xanthine-guanine phosphoribosyltransferase activity. The sixth revertant had mutated via CG----GC transversion back to the wild-type sequence. The results of this study define certain amino acid substitutions in the xanthine-guanine phosphoribosyltransferase polypeptide that are compatible with enzyme activity. These results also establish mutagen-induced reversion analysis as a sensitive and specific assay for mutagenesis in mammalian cells.

Peak levels of carbon tetrachloride (CCl4) as determined by head-space gas chromatography were observed 3-6 h following an acute oral dose of CCl4 in the blood, liver and fat of rats. Subsequently, there was a rapid decline of CCl4 levels. Conversely, serum activities of enzymes originating from the liver such as glutamate oxalacetate transaminase (GOT), glutamate pyruvate transaminase (GPT) and glutamate dehydrogenase (GDH) increased considerably and showed activity peaks between 12-48 h following CCl4 administration, indicating a delayed response of CCl4 on the activity levels of enzymes in the blood.