A series of monoclonal antibodies was prepared against tegumental and internal antigens of Fasciola hepatica by immunizing mice with whole adult-fluke homogenates prior to harvesting the splenic lymphocytes for fusion. Preliminary screening by the Indirect Fluorescent Antibody technique indicated the occurrence of discrete groups of monoclonals differing from one another in tissue-specificity but within which IFA labelling patterns were fairly consistent. Representative hybridomas for 5 of these groups were stabilized and used to produce ascites fluid in mice. By application of an immunogold labelling technique it was possible to map the distribution of antigens for which each monoclonal antibody had affinity throughout the tissues of 4-week and 12-week flukes. Several monoclonals specifically labelled antigenic determinants on the important tegumental antigen T1. However the distribution of gold colloid labelling suggested that epitopes other than that normally exposed to the infected host were recognized; and several monoclonals specifically attached to T1 antigen in the tegument of juvenile worms only. The glycocalyx of the gut and excretory system of flukes shared T1 antigenicity with the tegument. Monoclonal antibodies were produced against an internal immunogen associated with ribosomes and heterochromatin in active protein-producing cells, and against interstitial material of adult flukes. Monoclonals against antigens in parenchymal cell cytoplasm and in mature vitelline cells were recognized but the corresponding hybridomas were not stabilized.

Animals↗

PubMed1988

Enalapril & nifedipine in essential hypertension; synergism of the hypotensive effects in combination.

Twelve male hypertensive patients who had required enalapril and nifedipine to control their blood pressure were entered into a study of modified 2 x 2 factorial design (3 week study periods) to determine the effect of each drug separately and in combination. Factorial analysis indicated that enalapril alone (20 mg/d) lowered supine blood pressure by 10 +/- 2/8 +/- 1 mmHg, nifedipine alone (30 mg/d) lowered supine blood pressure by 11 +/- 2/8 +/- 1 mmHg and there was a positive interactive effect of 10 +/- 3/7 +/- 2 mmHg (P less than 0.001) such that the combination lowered supine blood pressure by 32 +/- 3/24 +/- 2 mmHg. The effects of the individual drugs were both significant (P less than 0.001) but did not differ from each other. Enalapril and nifedipine are both effective antihypertensive drugs and in some hypertensive patients their effects appear to be synergistic.

Aged↗

PubMed1988

Simple sequence DNA associated with near sequence identity of the 3'-flanking regions of rat cytochrome P450b and P450e genes.

In rat liver, the two major phenobarbital (PB)-inducible cytochrome P450s, P450b (P450IIB1), and P450e (P450IIB2), are encoded by approximately 2.1-kb mRNAs showing more than 97% nucleotide sequence identity. Almost half of the sequence differences are concentrated in two short divergent segments in exon 7. An additional 4.8-kb P450b/P450e RNA, inducible by Aroclor and by PB, hybridizes with a classical P450b probe and with the 3' extension of the PB23 insert, a cloned P450b-like cDNA (Affolter et al., DNA 5, 209-218, 1986). The 4.8-kb form has now been detected in several rats under a variety of induction conditions. DNA sequencing of the 5' portion of the PB23 insert showed it is derived from a P450b gene. The 4.8-kb RNA hybridized with an oligonucleotide probe that recognizes P450b mRNA, but did not hybridize detectably with one that recognizes P450e mRNA. The 4.8-kb RNA and the PB23 insert doubtless represent P450b RNAs polyadenylated at a downstream site. DNA sequence analysis of the PB23 3' extension (which represents the 3' end of the P450b gene) and of the P450e gene 3'-flanking region demonstrated that the near identity of the P450b and P450e genes extends for at least 920 bp beyond the major polyadenylation site. This region was doubtless part of the original duplication that gave rise to the P450b and P450e genes. A short divergent segment is present in the 3'-flanking region of near sequence identity; the segment is embedded in simple sequence DNA that contains a mixed alternating pyrimidine/purine tract.

Animals↗

PubMed1988

A constitutive member of the rat cytochrome P450IIB subfamily: full-length coding sequence of the P450IIB3 cDNA.

The prototypic members of the rat liver cytochrome P450IIB subfamily, P450b and P450e, have long been the subjects of intense interest, in part because they are highly inducible by phenobarbital (PB). We have previously cloned and sequenced an 858-bp cDNA fragment (the PB24 insert) that encodes the carboxy-terminal portion of a P450b/P450e-like protein, henceforth referred to as P450IIB3. A Bam HI-Eco RI fragment of the PB24 insert hybridizes with a 1.9-kb mRNA present constitutively in rat liver and not inducible by PB (Affolter et al., 1986). We have now obtained, from a lambda gt11 rat liver cDNA library, cDNA inserts corresponding to the complete coding sequence of the IIB3 mRNA. The 491-amino acid IIB3 protein sequence, deduced from the cDNA sequence, is 77% identical to that of P450b. Northern blot analysis, with a IIB3-specific oligonucleotide probe, confirmed the constitutive presence of the polyadenylated 1.9-kb IIB3 mRNA in male rat liver. The IIB3 mRNA was undetectable in the lung, kidney, and prostate. It was constitutively present, and not inducible by PB, in female rat liver. Our results demonstrate unequivocally the existence of a constitutive member of the rat P450IIB subfamily. The remarkable inducibility of the P450b/P450e genes is in striking contrast to the absence of a PB effect on IIB3 gene expression. The molecular basis for this difference remains to be revealed.

Amino Acid Sequence↗

PubMed1988

Transplacental induction of cytochromes P-450IA1 and P-450IA2 by polycyclic aromatic carcinogens: TCDD-binding protein level as the rate-limiting step.

Induction of cytochromes P-450c and P-450d have been compared in fetal and adult rat liver. A single dose of 3-methylcholanthrene (MC) 16 h before death, resulted in a pronounced accumulation of both mRNAs in adult liver. In contrast, treatment of fetuses with a single dose of MC did not increase the hepatic content in P-450c and P-450d mRNAs, whereas a 3-day treatment gave rise to a considerable accumulation of mRNAs. The fetal rat liver content in 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD)-binding protein was extremely low compared to the adult content. Pretreatment of fetuses with phenobarbital potentiated the inducing effect of MC upon P-450c and P-450d mRNA accumulation in relation to the duration of pretreatment, as well as increasing the hepatic content in TCDD-binding protein. Data strongly suggest that the hepatic TCDD-binding protein level is the rate-limiting step in MC induction of P-450c and P-450d in fetal but not in adult rat liver. In addition, phenobarbital and MC are potent inducers of the TCDD-binding protein in the fetal rat liver.

Animals↗

PubMed1988

Interaction of slow-channel calcium blocking drugs with sodium restriction, diuretics and angiotensin converting enzyme inhibitors.

The interactions of nifedipine with sodium restriction, diuretics and enalapril were studied using a 2 x 2 factorial design. Nifedipine lowered blood pressure to a greater extent than sodium restriction or hydrochlorothiazide. With both of these therapies there was a negative interactive term, which indicated that their combination had no greater effect than the use of nifedipine alone. Enalapril and nifedipine lowered blood pressure by 10 +/- 2/8 +/- 1 and 11 +/- 3/8 +/- 1 mmHg, respectively. The combination lowered blood pressure by 32 +/- 3/24 +/- 2 mmHg. The reasons for these negative and positive interactions are not clear, but may relate to interactions that regulate the availability of calcium for initiation of contraction in smooth muscle cells of the arterioles.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1988

Clinical strategies for obesity management.

Explore the source record for details and available documents.

Clinical Trials as Topic↗

PubMed1988

[Not Available].

Explore the source record for details and available documents.

Germany↗

PubMed1988

Interaction in hypertensive man between sodium intake, converting enzyme inhibitor (enalapril), plasma renin and blood pressure control.

Sixteen patients with hypertension entered a study in which the effects of enalapril were compared with sodium restriction, with the two in combination and with placebo using a balanced randomized double-crossover design. Each patient had four treatment phases of two weeks, duration which comprised a 2 x 2 factorial design as well as an initial period on sodium restriction and enalapril placebo. All patients received a reduced sodium diet and sodium intake was altered by slow Na tablets. Increasing sodium intake raised blood pressure similarly whether patients were receiving enalapril or its placebo. Enalapril lowered blood pressure to a similar extent in patients on either a low and high sodium intake. The combination of a low sodium intake and enalapril was additive and there was no interactive effect between the two therapies whether assessed by a linear or a logarithmic method. Plasma renin was increased by enalapril and lowered by increased sodium intake. These effects were additive and there was no interactive effect. Neither the initial plasma renin nor the rise in renin predicted which patients would respond to enalapril. Enalapril was an effective antihypertensive agent and its blood pressure-lowering effect and that of sodium restriction were additive.

Aged↗

PubMed1988

Clinical evaluation of a DNA probe assay for the Philadelphia (Ph1) translocation in chronic myelogenous leukemia.

We report the clinical evaluation of an improved DNA probe assay for the characteristic genetic marker of human CML, observed by cytogenetics and designated the Philadelphia chromosome (Ph1). The Ph1 chromosome results from the fusion of c-abl proto-oncogene sequences from chromosome 9 to phl gene sequence on chromosome 22. (The phl gene is often referred to as bcr. However, for clarity we prefer to reserve the designation "bcr" for the region within the phl gene in which translocation breakpoints have been found to occur. We also find it useful to distinguish between two such regions in phl, bcr-210 and bcr-190, named after the 210- and 190-kDa phl/abl fusion proteins resulting from translocations with breakpoints in the respective regions. We refer to the corresponding chromosomal translocations as Ph1(bcr-210) and Ph1(bcr-190).) DNA, extracted from peripheral blood (PB) or bone marrow (BM) and digested with restriction endonuclease BglII, is hybridized with a probe (phl/bcr-3) spanning a breakpoint cluster region within phl. Rearrangements are revealed by the presence of one or two novel junction fragments. Clinical specimens from leukemic patients with active disease were compared by cytogenetic and DNA probe analysis at seven centers in the United States and Europe. The probe assay identified the phl rearrangement in 190 of 191 cases of Ph1-positive CML, as well as in 12 of 27 clinically diagnosed CML specimens lacking a typical Ph1 chromosome. DNA rearrangements also were seen in two of six cases of Ph1-positive ALL. No false positive results were obtained among 93 non-leukemic controls. Mixing experiments showed that the DNA probe assay can detect as few as 1% leukemic cells in a specimen. A preliminary study of CML patients in remission after allogeneic BM transplantation revealed a small fraction of residual Ph1-positive leukemic cells in a significant number of such patients.

Blotting, Southern↗

PubMed1988

Assessing the value of employee training.

Scarce economic resources make cost-benefit assessment of employee training programs an important issue. It is helpful to review the role evaluation plays in training and apply cost-benefit assessment to management development programming.

Cost-Benefit Analysis↗