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PubMed2005

L-Arginine prevents air embolism-induced acute lung injury in rats.

OBJECTIVE: Pulmonary air embolism, causing vessel obstruction and primary or secondary reactions of blood, can lead to acute lung injury. In addition, nitric oxide has been known to play a key role in various causes of lung injury. In this study we employed the isolated rat lung model to investigate the effects of l-arginine on air embolism-induced lung injury. DESIGN: Randomized, controlled study. SETTING: Animal-care facility procedure room. SUBJECTS: Forty-two adult male Sprague-Dawley rats each weighing 250-350 g. INTERVENTIONS: Infusion of air at the rate of 0.25 mL/min for 1 min into the pulmonary artery in isolated and perfused rat lung resulted in pulmonary hypertension and lung edema. Air embolism elicited a significant increase in microvascular permeability as measured by the capillary filtration coefficient, lung weight gain, lung weight-to-body weight ratio, pulmonary arterial pressure, and protein concentration of bronchoalveolar lavage fluid. MEASUREMENTS AND MAIN RESULTS: Pretreatment with L-arginine (4 mmol/L) significantly attenuated the acute lung injury induced by air embolism as shown by a significant decrease in all of the assessed variables but did not alter the pulmonary arterial pressure (p < .05). The protective effect of l-arginine was blocked when N(G)-nitro-L-arginine methyl ester (5 mmol/L) was added. Pretreatment with N(G)-nitro-L-arginine methyl ester exacerbated air embolism-induced lung injury. CONCLUSIONS: Our findings suggest that L-arginine can prevent air embolism-induced lung injury.

Acute Disease↗

PubMed1990

Comparative evaluation on mouse nasal immunogenicity of arylmethane-, xanthene-, quinone-imine-, and acridine-dye-inactivated Sendai virus vaccines.

Twenty-seven kinds of organic dye-inactivated Sendai virus vaccines were prepared by treatment in dark at 23 C for 2 months or more, and selected with the high HA titers as a guide. Their nasal immunogenicities were examined in mice by contact infection and immunofluorescent method, and the relative merits of the dye-inactivants were determined. The strongest protection was elicited with acriflavine-, auramine O-, eosin Y-, neutral red-, night blue-, patent blue V-, thymol blue-, uranin-, and xylene cyanol FF-treated vaccines. Middling protective efficacy was induced by use of erio green B-, malachite green-, methyl green-, proflavine-, pyronin B-, and thionin-inactivated vaccines. Dye-inactivated vaccines that resulted in the weakest protection were Bindschedler's green-, bromothymol blue-, erythrosin B-, ethyl violet-, gallein-, light green SF yellowish-, methyl violet-, new methylene blue N-, phenol red-, rhodamine 6G-, spirit blue- and victoria blue B-treated ones. Serum HI titers developed by nasal vaccination were variable, and rose still more in most vaccinated groups postexposure. Elicitation of the most effective nasal immunogenicity in dye-inactivated vaccines appeared to depend on selective modification of capsid protein or ribose in viral core with dyes possessing definite functions, despite the different molecular structures.

Animals↗

PubMed2005

Nitric oxide synthase inhibition reduces the O2 cost of force development in rat hindlimb muscles pump perfused at matched convective O2 delivery.

Nitric oxide (NO) is a physiological mediator of skeletal muscle function. Specifically, NO affects cellular respiration and muscle contractility; however, the reduced blood flow and convective O2 delivery that result from impaired vasodilatation when NO synthase (NOS) is inhibited in vivo have obscured past interpretations of the effects of NO. Therefore, we studied the effect of NOS inhibition in an in situ pump-perfused rat hindlimb to test the hypothesis that NOS inhibition would improve contractile and aerobic metabolic performance. Pump perfusion permitted matching of convective O2 delivery (516 +/- 16 micromol O2 min(-1) (100 g)(-1); mean +/- s.e.m.) between groups, allowing us to investigate the effects of NOS inhibition independent of this variable. Three groups were studied. The perfusate of one group was treated with both adenosine (0.01 mm) and the NOS inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME; 1 mm). Adenosine is a vasodilator that can act through both NO-dependent and -independent pathways; the NO-independent vasodilatory action of adenosine allowed us to match the perfusion rate and convective O2 delivery in this L-NAME group to those of the other groups. In the second group the perfusate was treated with adenosine only (Ado). In the third group the perfusate received no treatment and served as a control (Con). Oxygen consumption (VO2) was on average 26 and 14% lower during the contraction bout in L-NAME and Ado, respectively, versus Con. In Ado, lactate efflux was similar to Con and force was reduced in proportion to versus Con, whereas L-NAME was associated with a 32% lower lactate efflux and similar force to Con. Therefore, the lower :force development ratio in the L-NAME group demonstrates that the O2 cost of force development is reduced by NOS inhibition independent of convective O2 delivery.

Adenosine↗

PubMed1998

Microcosm enrichment of biphenyl-degrading microbial communities from soils and sediments.

A microcosm enrichment approach was employed to isolate bacteria which are representative of long-term biphenyl-adapted microbial communities. Growth of microorganisms was stimulated by incubating soil and sediment samples from polluted and nonpolluted sites with biphenyl crystals. After 6 months, stable population densities between 8 x 10(9) and 2 x 10(11) CFU/ml were established in the microcosms, and a large percentage of the organisms were able to grow on biphenyl-containing minimal medium plates. A total of 177 biphenyl-degrading strains were subsequently isolated and characterized by their ability to grow on biphenyl in liquid culture and to accumulate a yellow meta cleavage product when they were sprayed with dihydroxybiphenyl. Isolates were identified by using a polyphasic approach, including fatty acid methyl ester (FAME) analysis, 16S rRNA gene sequence comparison, sodium dodecyl sulfate-polyacrylamide gel electrophoresis of whole-cell proteins, and genomic fingerprinting based on sequence variability in the 16S-23S ribosomal DNA intergenic spacer region. In all of the microcosms, isolates identified as Rhodococcus opacus dominated the cultivable microbial community, comprising a cluster of 137 isolates with very similar FAME profiles (Euclidean distances, <10) and identical 16S rRNA gene sequences. The R. opacus isolates from the different microcosms studied could not be distinguished from each other by any of the fingerprint methods used. In addition, three other FAME clusters were found in one or two of the microcosms analyzed; these clusters could be assigned to Alcaligenes sp., Terrabacter sp., and Bacillus thuringiensis on the basis of their FAME profiles and/or comparisons of the 16S rRNA gene sequences of representatives. Thus, the microcosm enrichments were strongly dominated by gram-positive bacteria, especially the species R. opacus, independent of the pollution history of the original sample. R. opacus, therefore, is a promising candidate for development of effective long-term inocula for polychlorinated biphenyl bioremediation.

Bacterial Typing Techniques↗

PubMed2001

Pathology and pathogenesis of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver and among the most common cancers worldwide. The distribution pattern of HCC shows geographical variation and its pathogenesis is multifactorial. Environmental, infectious, nutritional, metabolic, and endocrine factors contribute directly or indirectly to hepatocarcinogenesis. The synchronous occurrence of different risk factors, such as chronic viral hepatitis B and C, aflatoxin exposure, alcohol consumption or iron overload, in a single patient or patient population further increases the risk. HCC is commonly associated with chronic hepatitis and liver cirrhosis. Different genes have been implicated in the pathogenesis of HCC, and may be divided into four major groups: genes regulating DNA damage response; genes involved in cell cycle control; genes involved in growth inhibition and apoptosis, and genes responsible for cell-cell interaction and signal transduction. Hepatocarcinogenesis is mediated by loss of heterozygosity, somatic mutation, de novo methylation, and/or functional inactivation. As yet, there is no evidence for an ordered sequence of genomic events leading to hepatocarcinogenesis. The pattern of genomic alterations shows great variability, often between two different HCCs from a single patient. HCC evolves from precancerous lesions, and well-differentiated HCC further progresses to a less differentiated form. However, there is still great need for the definition of objective morphological, phenotypic and genetic markers for the progression of HCC.

Apoptosis↗

PubMed2004

Effects of psyllium on plasma total and lipoprotein cholesterol and hepatic cholesterol in hamsters fed n-3 PUFA or n-6 PUFA with high cholesterol levels.

This study was conducted to determine whether psyllium is known to alter cholesterol metabolism modulate the hypercholesterolemic effect of a high cholesterol, n-3 polyunsaturated fatty acids (PUFA) diet in hamsters. Concentrations of plasma, hepatic total cholesterol and lipoprotein cholesterol were measured in male hamsters fed an n-3 PUFA plus psyllium (8%, wt/wt) diet combined with variable levels of cholesterol (0, 0.05, 0.1%, wt/wt) or a cholesterol-enriched (0.2%, wt/wt) n-3 PUFA or n-6 PUFA diet that contained either 8% methyl cellulose or psyllium for 4 weeks. In the n-3 PUFA-fed hamsters, we have found that psyllium was able to reduce plasma total cholesterol and low density lipoprotein (LDL)-cholesterol significantly when 0.1% cholesterol was added to the diet. In contrast, the effects of psyllium were not seen in the n-3 PUFA-fed hamsters without dietary cholesterol or with 0.05% dietary cholesterol. However, no matter in the presence of psyllium or not, the increase of plasma total cholesterol, very-low-density lipoprotein (VLDL)-cholesterol, LDL-cholesterol and high-density lipoprotein (HDL)-cholesterol levels was depend on the content of dietary cholesterol. Although the cholesterol diet increased the liver total cholesterol level, 80 g psyllium/kg diet resulted in a significantly lower concentration of liver total cholesterol in the cholesterol-fed hamsters. In the second experiment, we have also found that psyllium feeding lowered significantly plasma total cholesterol and VLDL-cholesterol concentrations in hamsters fed n-3 PUFA but not in those fed n-6 PUFA. However, the levels of plasma total cholesterol, VLDL-cholesterol and LDL-cholesterol levels of the (n-6) PUFA-fed hamsters were significantly lower than those in the (n-3) PUFA-fed hamsters in the absence or presence of dietary psyllium. Our data also showed that hamsters fed both high-cholesterol n-3 PUFA and n-6 PUFA diets had a significant decrease in hepatic cholesterol with intake of psyllium. Liver total cholesterol concentrations were significantly lower in n-3 PUFA-fed hamsters compared with the n-6 PUFA-fed groups. Therefore, these data may contribute to understanding the interactive effect of psyllium and cholesterol or the type of fat on plasma and liver cholesterol in hamsters.

Animals↗

PubMed2003

Nitric oxide produced by the enterocyte is involved in the cellular regulation of ion transport.

The role of nitric oxide (NO) in the intestinal basal ion transport and under conditions of enterotoxin-induced ion secretion is controversial. Namely it is not clear whether NO enhances or counteracts intestinal ion secretion and whether the effects on transport result from a direct interaction with the enterocyte. The cell origin of NO is also unclear. We have tested the hypothesis that NO produced by the enterocyte directly regulates ion transport processes either in basal condition or in response to cholera toxin-induced secretion. Electrical variables reflecting transepithelial ion transport were measured in Caco-2 cell monolayers mounted in Ussing chambers exposed to the NO synthase inhibitor Nomega-nitro-l-arginine methyl ester, in the presence or absence of cholera toxin. cAMP concentrations were also measured. NO release was determined by nitrite-nitrate concentration. NO synthase activities were assayed by Western blot analysis. Nomega-nitro-l-arginine methyl ester had a secretory effect, as judged by increased basal short-circuit current and cAMP concentration. It also increased cholera toxin-induced electrical response and cAMP production. Either cholera toxin or the cAMP analog 8-bromo-cAMP induced a rapidly progressive and Ca2+-dependent increase in NO concentration, suggesting a homeostatic up-regulation of the constitutive form of NO synthase. Western blot analysis showed an increase in constitutive NO synthase enzyme isoform. These results indicate that the enterocyte regulates its own ion transport processes, either in basal condition or in the presence of active secretion, through the activation of a constitutive NO synthase-NO pathway, functioning as a braking force of cAMP-induced ion secretion.

Biological Transport↗

PubMed1990

Structure of the lipophosphoglycan from Leishmania major.

The major cell surface glycoconjugate of the parasitic protozoan Leishmania major is a heterogeneous lipophosphoglycan. It has a tripartite structure, consisting of a phosphoglycan (Mr 5,000-40,000), a variably phosphorylated hexasaccharide glycan core, and a lysoalkylphosphatidylinositol (lysoalkyl-PI) lipid anchor. The structures of the phosphoglycan and the hexasaccharide core were determined by monosaccharide analysis, methylation analysis, fast atom bombardment-mass spectrometry, one- and two-dimensional 500-MHz (correlated spectroscopy (COSY), homonuclear Hartmann-Hahn spectroscopy (HOHAHA] 1H NMR spectroscopy, and exoglycosidase digestions. The phosphoglycan consists of eight types of phosphorylated oligosaccharide repeats which have the general structure, [formula: see text] where R = H, Galp(beta 1-3), Galp(beta 1-3)Galp(beta 1-3), Arap(alpha 1-2)Galp(beta 1-3), Glcp(beta 1-3)Galp(beta 1-3), Galp(beta 1-3)Galp(beta 1-3)Galp(beta 1-3), Arap(alpha 1-2)Galp(beta 1-3)Galp(beta 1-3), or Arap(alpha 1-2)Galp(beta 1-3)Galp(beta 1-3)Galp(beta 1-3)Galp(beta 1-3), and where all the monosaccharides, including arabinose, are in the D-configuration. The average number of repeat units/molecule (n) is 27. Data are presented which suggest that the nonreducing terminus of the phosphoglycan is capped exclusively with the neutral disaccharide Manp(alpha 1-2)Manp alpha 1-. The structure of the glycan core was determined to be, [formula: see text] where approximately 60% of the mannose residues distal to the glucosamine are phosphorylated and where the inositol is part of the lysoalkyl-PI lipid moiety containing predominantly 24:0 and 26:0 alkyl chains. The unusual galactofuranose residue is in the beta-configuration, correcting a previous report where this residue was identified as alpha Galf. Although most of the phosphorylated repeat units are attached to the terminal galactose 6-phosphate of the core to form a linear lipophosphoglycan (LPG) molecule, some of the mannose 6-phosphate residues may also be substituted to form a Y-shaped molecule. The L. major LPG is more complex than the previously characterized LPG from Leishmania donovani, although both LPGs have the same repeating backbone structure and glycolipid anchor. Finally we show that the LPG anchor is structurally related to the major glycolipid species of L. major, indicating that some of these glycolipids may have a function as precursors to LPG.

Animals↗

PubMed1983

Ion-pair partition chromatography of mefenamic acid with tetraalkylammonium cations: development of analytical method from extraction data.

The ion-pair partition properties of mefenamic acid with the methyl, ethyl, n-propyl, and n-butyl homologs of tetraalkylammonium cation were studied in relation to a model of an assay procedure for acidic drugs. Variables studied included identity and concentration of pairing ion and composition of extracting solvents. Resulting data were used to develop a partition chromatographic assay procedure. Standard recoveries averaged 99.01 +/- 0.82%. Assays of commercial capsules were reproducible.

Capsules↗

PubMed1996

Severe and mild mutations in cis for the methylenetetrahydrofolate reductase (MTHFR) gene, and description of five novel mutations in MTHFR.

Methylenetetrahydrofolate reductase (MTHFR) catalyzes the synthesis of 5-methyltetrahydrofolate, a methyl donor in the conversion of homocysteine to methionine. Patients with severe MTHFR deficiency have hyperhomocysteinemia, hypomethioninemia, and a range of neurological and vascular findings with a variable age at onset. We have previously described nine mutations in patients with severe MTHFR deficiency. A mild form of MTHFR deficiency, associated with a thermolabile enzyme, has been proposed as a genetic risk factor for cardiovascular disease and for neural tube defects. We have shown that a common missense mutation (an alanine-to-valine substitution) encodes this thermolabile variant. We now report an additional five mutations causing severe MTHFR deficiency and an analysis of genotype (alanine/valine status) and enzyme thermolability in 22 patients with this inborn error of metabolism. Six of these patients have four mutations in the MTHFR gene-two rare mutations causing severe deficiency and two mutations for the common alanine-to-valine mutation that results in thermolability. Even in severe MTHFR deficiency, the thermolabile variant is frequently observed, and there is a strong relationship between the presence of this variant and increased enzyme thermolability.

Adolescent↗

PubMed2000

Sensitivity analysis of mercury human exposure.

We present a comprehensive analysis of the sensitivity of mercury (Hg) human exposure to environmental variables using a multimedia model of the fate and transport of Hg in the environment. The results of the analysis show that the Hg dose is most sensitive to the lake pH, the burial rate of Hg adsorbed to sediments, and the chemical speciation of Hg emissions to the atmosphere. The lake pH has a strong non-linear effect on the methylation rate and bioaccumulation of Hg in fish. The burial of sediments is a major pathway for removing Hg from the lake cycling. The speciation of Hg emissions is important because Hg(II) is deposited much more rapidly than Hg(0). These results highlight the importance of key variables that should be investigated through well-designed field programs, so that we can minimize the overall uncertainties associated with the modeling of mercury fate and transport.

Confounding Factors, Epidemiologic↗

PubMed1975

Genetic variability of Chlamydomonas reinhardtii induced by six urea derivatives.

The lethal and mutagenic effect of six urea derivatives applied to the cells of Chlamydomonas reinhardtii Dang was investigated. The mutagenic effect of two N-alkylnitroso derivatives (N-methyl-N-nitroso- and N-ethyl-N-nitrosourea), two monoalkyl derivatives (N-methyl- and N-ethylurea) and two dialkyl derivatives (N,N'-dimethyl- and N,N'-diethylurea) was compared at equal molar concentrations and different cell survival or at equitoxic concentrations, i.e. at equal survival. The former type of appraisal shows the alkylnitroso derivatives to be strong mutagenic agents, exceeding in their effect several times both monoalkyl- and dialkyl derivatives. MNU is seen to be a stronger mutagen than ENU. Alkyl derivatives are generally weak mutagens, the strongest being DEU and the least potent DMU. On using the latter type of evaluation MNU is seen to be clearly the strongest mutagen while the other five compounds, including ENU, have, at equitoxic concentrations, approximately the same effect.

Chlamydomonas↗

PubMed2003

Acute and subchronic MPTP administration differentially affects striatal glutamate synaptic function.

We previously reported that 1 month following unilateral loss (>95%) of striatal dopamine, there is an increase in striatal glutamate function as measured by in vivo microdialysis and quantitative immuno-gold electron microscopy, Neuroscience 88, 1-16). The goal of this study was to determine the effect of bilateral loss of striatal dopamine on striatal glutamate function following acute or subchronic administration of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to C57/B6J mice. Animals were administered either single injections (ip) of 30 mg/kg/day for 7 days (subchronically treated group) or 20 mg/kg x 4 doses every 2 h (acutely treated group) of the toxin or saline. One month following the first injection, there was a 44 and 65% loss in the relative density of tyrosine hydroxylase (TH) immunolabeling within the dorsolateral striatum in the subchronically and acutely MPTP-treated groups compared to the saline group, respectively. There was a decrease in the basal level of extracellular glutamate within the striatum in the subchronically MPTP-treated animals compared to an increase in the acutely treated group in relationship to the saline group. Ultrastructurally, only in the acutely MPTP-treated group was there a decrease in the density of glutamate immunolabeling within nerve terminals associated with an asymmetrical synaptic contact in the dorsolateral striatum compared to either the subchronic or saline groups. In addition, there was a decrease in the relative density of GluR-2/3 subunit immunolabeling within the dorsolateral striatum in the acute MPTP compared to the saline group. These data indicate that differences in striatal glutamate function appear to be associated with the dosing interval of MPTP administration and the variable loss of striatal TH immunolabeling.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1989

Predominant immunoglobulin gene rearrangements in two patients with immunodeficiency: restricted use of V gene segments and DNA hypermethylation.

The majority of common variable immunodeficiencies (CVID) is caused by intrinsic B cell defects which impede distinct stages of B cell differentiation. B cell differentiation is accompanied by the rearrangement of immunoglobulin (Ig) genes. The first step in the rearrangement process is the assembly of IgH genes, and subsequently, IgL genes are rearranged. During B cell maturation, Ig genes are demethylated in a stepwise, locus-specific manner. Here, we examined the Ig gene rearrangements of four patients with classical CVID and of one child suffering from an unusual immunodeficiency associated with CD5+ B cell lymphocytosis. In one of the four adult patients with CVID, we observed a predominant type of VHDJH-gene rearrangement. In the child, different polyclonal VHDJH-gene rearrangements were found together with a predominant type of kappa light chain gene rearrangement. The rearranged kappa chain genes were methylated (as in the pre-B cell stage). These findings together with the cell phenotype analysis and the clinical course of the disease in the child suggests that in some patients with primary immunodeficiency a maturation arrest may occur in B cells leading to a predominant Ig V gene rearrangement.

Adolescent↗

PubMed1996

Effects of 5-HT4 receptor antagonists on rat behaviour in the elevated plus-maze test.

The anxiolytic-like effects of a variety of 5-HT receptor agonists and antagonists have been intensively studied in animal models. However, no direct effects of agents modulating 5-HT4 receptors have been reported, in spite of their suggestive location in the brain. The objective of the present study was the determination of the effects of two selective 5-HT4 receptor antagonists, SB 204070 [1-butyl-4-piperidinylmethyl)-8-amino-7-chloro-1,4-benzodioxan-5-carboxylate] and GR 113808 [[1-[2-methylsulphonyl)amino]ethyl]-4-piperidinyl]methyl 1-methyl-1 H-indole-3-carboxylate], in the elevated plus-maze test in rats. Results have shown that both 5-HT4 receptor antagonists exhibit an anxiolytic-like profile, although only at the dose of 1.0 mg/kg (s.c.). At this dose, both compounds significantly increased the percentage of time spent in open arms exploration, while other variables evaluated remained unaffected at the dose range tested. Results suggest that 5-HT4 receptor antagonists could have some anxiolytic-like properties, although their effects seem more limited and less consistent than those presented by classic anxiolytics, such as diazepam. However, they are similar to those exhibited by granisetron [endo-1-methyl-N-(9-methyl-9-azabicyclo[3.3.1]non-3-yl)-1 H-indazole-3-carboxamide], a 5-HT3 receptor antagonist.

Animals↗

PubMedDate not supplied

Transcription of integrated MMTV LTR DNA in fibroblast clones is not associated with DNA methylation but with the integration site.

By transfecting 3T3 TK- fibroblasts with a plasmid DNA containing the MMTV LTR promotor and the thymidine kinase gene, we have isolated TK+ clones that contain only one copy of the recombinant DNA. The newly acquired DNA is integrated at different sites in each TK+ clones and can be amplified as a tandem repeat in some cases. The basal level of expression of the newly acquired LTR sequence is variable among the TK+ clones studied. Among those producing detectable amounts of MMTV RNA, we found that transcription is initiated from the LTR promotor and that the synthesis is stimulated by a short dexamethasone treatment. In addition, the presence of tandem repeated LTR DNA does not amplify the MMTV RNA synthesis. Endogenous LTR sequences have been found to be methylated, whereas we show that the newly integrated sequences, both as single copy and tandem repeats, remain unmethylated. Thus, non-methylation of MMTV LTR DNA is necessary but not significant to allow its transcription. Our results suggest that the level of LTR promotor activity could be modulated by the nature of its integration site within the cellular genome.

Animals↗

PubMed2000

O-glycan variability of egg-jelly mucins from Xenopus laevis: characterization of four phenotypes that differ by the terminal glycosylation of their mucins.

Eggs from Xenopus laevis are surrounded by several layers of jelly that are needed for proper fertilization. Jelly coat is composed of high-molecular-mass glycoconjugates to which are bound many globular proteins. O-glycans released from the jelly coat of X. laevis have been partially described in previous studies. In this study, we compared the glycosylation pattern of the egg jelly coat isolated from six specimens of X. laevis. The O-glycans were released from jelly coats by alkali/borohydride treatment. Structural characterization was performed through a combination of one- and two-dimensional (1)H-NMR and methylation analysis. This allowed the description of a new family of sulphated O-glycans present in jelly coats of all X. laevis. However, the jelly O-glycans showed a low extent of polymorphism between specimens. This intra-specific variability was restricted to the terminal substitution of O-linked oligosaccharides. The differential expression of two glycosyltransferase [an alpha-(1-->4) galactosyltransferase and an alpha-(1-->3) fucosyltransferase] activities resulted in the characterization of four phenotypes of X. laevis. Furthermore, electrophoretic analysis suggested that the high-molecular-mass fraction of jelly coat was mostly composed of mucin-type glycoproteins. Blot analysis with lectins confirmed that the glycan variability was borne by these mucin-type components. However, fertilization assays suggested that the glycan polymorphism had no repercussion on egg fertilizability.

Animals↗

PubMed1984

Primary liver cancer. An Eastern Cooperative Oncology Group Trial.

One hundred ninety-two patients with unresectable primary liver cancer studied by members of the Eastern Cooperative Oncology Group (ECOG) were evaluable in a prospectively randomized clinical trial. Patient discriminants such as performance status were carefully evaluated to assess their influence on prognosis and to evaluate the importance of patient status on response and survival. Patients who were totally bedridden or with signs of overt liver failure were not entered on study. The median survival time for all evaluable previously untreated patients was 17 weeks (19 weeks for North American and European, and 10 weeks for South African black patients). Among the South African patients, however, there was a significantly larger proportion with an initially poor performance status. Prognostic variables (performance status, jaundice, and reduced appetite) dominate any differences among the treatments studied. Among North American and European patients on intravenous (IV) 5-fluorouracil (5-FU) + Methyl-CCNU (MeCCNU) + Adriamycin (ADM, doxorubicin), the 19% response rate is offset by 63% with severe toxicity and a median survival time of only 17 weeks, making this treatment unacceptable clinically. The median survival time of North American and European patients treated with IV 5-FU +/- MeCCNU was 28 weeks in contrast to a median survival time of 12 weeks with ADM (P less than or equal to 0.01). EST 2273 was the ECOG study of patients with primary liver cancer. The results of the first part of the trial were published in 1978. This report updates those findings and reports the results of patients entered subsequently on the second part of that study after it was amended in 1979. With more than 300 evaluable patients in EST 2273, this duet of studies is the largest ever conducted in patients with primary liver cancer, and draws a new baseline from which to measure the disease and its response to treatment.

Adenoma, Bile Duct↗