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Biomedical subjects

H J Brown

Publications and source records attributed to H J Brown.

At least 19 recordsLinked to original sources

Phytoextraction of Pb and Cd from a superfund soil: effects of amendments and croppings.

In a growth chamber, maize (Zea mays) and Indian mustard (Brassica juncea) were grown over two croppings in soil from a Superfund site (PbTotal = 65,200 mg/kg and CdTotal = 52mg/kg). Soil treatments consisted of ethylenediaminetetraacetic acid, sodium citrate and composted sewage sludge, each at two rates (EDTA .05%, EDTA .2%, citrate .05%, citrate .2%, CSS 5% and CSS 10%, respectively). In most cases, the EDTA and citrate treatments were superior in terms of solubilizing soil Pb for root uptake and translocation into above-ground biomass. In the first maize crop, the EDTA .2% treatment resulted in 2,435 and 9,389mg/kg Pb in shoot and root tissues, respectively. The CSS treatments typically resulted in lowest Pb and Cd removal efficiencies. Lead remaining in the soil after two croppings was mainly associated with the carbonate, organic, and residual fractions, which represent the less bioavailable forms. Soil Cd was generally more mobile for plant uptake than soil Pb. The EDTA .2% and citrate treatments were most successful in promoting Cd uptake by both maize and mustard. Although Pb concentrations (mg/kg tissue) were lower for maize than mustard, the former removed more total Pb (0.2 mg per pot, mean over all treatments), compared to mustard (0.03 mg), by virtue of its higher biomass production.

Biodegradation, Environmental↗

Transposons Tn1696 and Tn21 and their integrons In4 and In2 have independent origins.

The first 13.6 kb of the mercury and multidrug resistance transposon Tn1696, which includes the class 1 integron In4, has been sequenced. In4 is 8.33 kb long and contains the 5'-conserved segment (5'-CS) and 2.24 kb of the 3'-conserved segment (3'-CS) flanking four integrated cassettes. The 3'-CS region is followed by one full copy and an adjacent partial copy of the insertion sequence IS6100 flanked, in inverse orientation, by two short segments (123 and 152 bp) from the outer right-hand end of class 1 integrons. This structure is representative of a distinct group of class 1 integrons that differs from In2, found in Tn21, and other related class 1 integrons. In4 does not include transposition genes but is bounded by characteristic 25-bp inverted repeats and flanked by a direct duplication of 5 bp of the target sequence, indicating that it was inserted by a transpositional mechanism. In4 lies between the resII and resI sites of a backbone mercury resistance transposon which is >99.5% identical to Tn5036. Although Tn21 and Tn1696 are both classified as members of the Tn21 subfamily of the Tn3 transposon family, the backbone mercury resistance transposons are only 79 to 96% identical. Tn21 also contains a region of about 0.7 kb not found in Tn1696. The integrons In2 and In4 carrying the antibiotic resistance genes have been inserted at different locations into distinct ancestral mercury resistance transposons. Thus, Tn21 and Tn1696 have independent histories and origins. Other transposons (Tn1403 and Tn1412) that include a class 1 integron also have independent origins. In all except Tn21, the integron is located within the res region of the backbone transposon.

Anti-Infective Agents, Local↗

Transcription activation of polyadenylated nuclear rna by rta in human herpesvirus 8/Kaposi's sarcoma-associated herpesvirus.

Human herpesvirus 8 (HHV-8) (also known as Kaposi's sarcoma-associated herpesvirus) encodes a novel noncoding polyadenylated nuclear (PAN) RNA (also known as T1.1 or nut-1) during the early phase of lytic replication. PAN RNA is the most abundant transcript of HHV-8, comprising 80% of total poly(A)-selected transcripts in HHV-8-infected cells during lytic replication. We directly measured the abundance of PAN RNA by visualizing 1.1- to 1.2- kb PAN RNA in an ethidium bromide-stained gel from poly(A)-selected RNA. We further pursued the mechanisms by which PAN RNA expression is induced to such high levels. rta, an immediate-early gene of HHV-8, is a transactivator that is sufficient and necessary to activate lytic gene expression in latently infected cells. Ectopic expression of Rta was previously shown to induce PAN RNA expression from the endogenous viral genome and activate the PAN promoter in a reporter system. Here, we have identified the Rta-responsive element (RRE) in the PAN promoter. Deletion analysis revealed that the RRE is present in a region between nucleotides -69 and -38 of the PAN promoter. A promoter construct containing the 69 nucleotides upstream of the transcription start site of the PAN promoter was activated by Rta in the absence or presence of the HHV-8 genome. Rta activated the PAN promoter up to 7,000-fold in 293T cells and 2,000-fold in B cells. Electrophoretic mobility shift assays demonstrated that Rta formed a highly stable complex with the RRE of the PAN promoter. Our study suggests that Rta can induce PAN RNA expression by direct binding of Rta to the RRE of the PAN promoter. This study has highlighted an important mechanism controlling PAN RNA expression and also provides a model system for investigating how Rta transactivates gene expression during lytic replication.

Animals↗

Tanner's story: a phenomenologic stance towards newborn death.

A phenomenologic stance is explored as a perspective from which to develop personal knowledge for nursing with families experiencing perinatal loss. The author's experience of newborn death is analyzed using van Manen's existential themes. An essential theme--validating motherhood--emerges from an analysis based on van Manen's lifeworld existential themes. Phenomenologic reflection is presented as a path to self-understanding and reflection, which may inform personal knowledge for nursing practice and the relationships nurses nurture with families.

Adaptation, Psychological↗

The integrons In0, In2, and In5 are defective transposon derivatives.

The class 1 integrons In0, In2, and In5, found in different locations in pVS1, Tn21, and pSCH884, have closely related structures. All three integrons contain an insertion sequence, IS1326, that is a new member of the IS21 family. IS1326 has caused deletions of adjacent 3'-conserved segment and transposition module sequences, and all three integrons retain a complete copy of only one of four genes required for transposition of related transposons and are thus defective transposon derivatives. In2 contains an additional insertion sequence, IS1353, located within IS1326. IS1353 is a member of the IS3 family and appears to have been acquired after the integron was inserted into an ancestral mercury resistance transposon to create the ancestor of Tn21 and several other transposons that are close relatives of Tn21.

Amino Acid Sequence↗

An inhibitor domain in c-Fos regulates activation domains containing the HOB1 motif.

The c-Fos protein has three activation modules at its C-terminus, two of which contain motifs (HOB1 and HOB2) which are also present in the activation domains of c-Jun. Here we show the existence of two additional activation modules at the N-terminus of c-Fos, one of which contains a second HOB1 motif (HOB1-N). The N-terminus also contains an inhibitor domain (ID1) which silences HOB1 activity. GAL4 fusion experiments showed that ID1 can specifically silence HOB1-containing activation domains from c-Fos or c-Jun when linked in cis, but will not affect other distinct activation domains. The c-Fos related protein, FosB, also contains an inhibitor domain. Mutagenic and deletion analyses identify an inhibitor motif (IM1) conserved between c-Fos and FosB, which is required for inhibitor function. Mutagenesis of IM1 enhances the ability of c-Fos to activate an AP1 bearing promoter. Finally, squelching experiments suggest that c-Fos ID1 binds a limiting protein involved in inhibition. These results demonstrate the existence of a new class of inhibitor domain within transcriptional activators, which acts in a sequence specific manner to inhibit a subset of activation domains.

Amino Acid Sequence↗

Phosphorylation of the c-Fos and c-Jun HOB1 motif stimulates its activation capacity.

The c-Fos and c-Jun proteins bind an AP1 site and activate transcription synergistically. These two proteins have a common activation domain which has two co-operating motifs, HOB1 and HOB2. The HOB1 motif of c-Jun includes S73 which is required for Ha-Ras-induced super-activation and phosphorylation by MAP kinase-like enzymes. Since c-Fos HOB1 has a conserved Thr residue (T232) analogous to c-Jun S73 we have proposed that c-Fos HOB1 will be regulated in the same way as c-Jun HOB1. Here we show that the HOB1-containing activation domain of c-Fos is stimulated by Ha-Ras in vivo and phosphorylated by a MAP kinase family member in vitro and that mutating T232 to Ala abolishes both functions. Collectively these results suggest that phosphorylation of the HOB1 motif increases its activation capacity. To provide direct evidence for this we change the context of c-Fos T232 to a PKA recognition site, and show that HOB1 activity is now stimulated by the catalytic subunit of PKA. This 'PKA specificity' experiment represents a novel and powerful way to analyse phosphorylation events involved in a variety of biological functions.

Amino Acid Sequence↗

Integrons found in different locations have identical 5' ends but variable 3' ends.

The positions of the outer boundaries of the 5'- and 3'-conserved segment sequences of integrons found at several different locations have been determined. The position of the 5' end of the 5'-conserved segment is the same for six independently located integrons, In1 (R46), In2 (Tn21), In3 (R388), In4 (Tn1696), In5 (pSCH884), and In0 (pVS1). However, the extent of the 3'-conserved segment differs in each integron. The sequences of In2 and In0 diverge first from the conserved sequence, and their divergence point corresponds to the 3'-conserved segment endpoint defined previously (H.W. Stokes and R.M. Hall, Mol. Microbiol. 3:1669-1683, 1989), which now represents the endpoint of a 359-base deletion in In0 and In2. The sequence identity in In3, In1, In4, and In5 extends beyond this point, but each sequence diverges from the conserved sequence at a different point within a short region. Insertions of IS6100 were identified adjacent to the end of the conserved region in In1 and 123 bases beyond the divergence point of In4. These 123 bases are identical to the sequence found at the mer end of the 11.2-kb insertion in Tn21 but are inverted. In5 and In0 are bounded by the same 25-base inverted repeat that bounds the 11.2-kb insert in Tn21, and this insert now corresponds to In2. However, while In0, In2, and In5 have features characteristic of transposable elements, differences in the structures of these three integrons and the absence of evidence of mobility currently preclude the identification of all of the sequences associated with a functional transposon of this type.

Base Sequence↗

Primary structure of a Plasmodium falciparum rhoptry antigen.

The high-molecular-weight rhoptry complex of Plasmodium falciparum consists of 3 non-covalently associated polypeptides of 150, 135 and 105 kDa. We present the complete nucleotide sequence of the 105-kDa (RhopH3) component of this complex derived from analysis of genomic and cDNA clones. The genomic structure is unusually complex for P. falciparum, consisting of 7 exons including 2 mini-exons of 19 and 21 amino acids. The sequence lacks tandem repeats and is conserved among several parasite isolates. B cell epitopes that induce antibody responses during natural infection were mapped to five different regions of the polypeptide.

Amino Acid Sequence↗

Chromosome 9 from independent clones and isolates of Plasmodium falciparum undergoes subtelomeric deletions with similar breakpoints in vitro.

We show that chromosome 9 in all isolates and clones of Plasmodium falciparum examined so far exists as one of two distinctly different forms, a large form about 1.9 megabases long or a smaller form about 25% shorter. Physical maps of chromosome 9 from independent clones with large and small forms of chromosome 9, and from an isolate with the large form and 3 derived clones with the small form reveal the underlying structural basis of this size polymorphism. The small form differs from the large only in that there are subtelomeric deletions at each end, one of these deletions involving about 0.45 megabases. Remarkably, the breakpoints map within about +/- 1% of the total chromosome length for each of these populations. We discuss some possible mechanisms for this.

Animals↗

Supraorbital photoplethysmographic monitoring during carotid endarterectomy with the use of an internal shunt: an added dimension of safety.

Photoplethysmograph (PPG) has added a new dimension of safety to carotid endarterectomy operations. Used to monitor adequate shunt blood flow during carotid endarterectomy, the PPG has proven to be a sensitive, reliable, and accurate device. Temporary intraoperative shunt occlusion is immediately indicated by marked amplitude reductions in the supraorbital artery pulse waveform. The cause of the occlusion is usually found to be impingment of the distal end of the shunt against the arterial wall, which is easily corrected by proximal positioning of the shunt. Also, occasionally occlusion will occur from kinking of the internal carotid artery distal to the shunt, which is corrected by slight proximal retraction on the artery. Repositioning retractors in the upper extent of the operative field will alleviate any occlusions from retractor pressure on the internal carotid artery. Without a method of sensing hemodynamically significant decreases in shunt flow during operation for carotid endarterectomy, there exists a risk of prolonged unrecognized intraoperative cerebral ischemia.

Blood Vessel Prosthesis↗

Continuous oculoplethysmographic monitoring during carotid endarterectomy.

Oculoplethysmography has moved from the noninvasive vascular diagnostic laboratory to the operating room and is serving a new role in monitoring internal carotid shunt blood flow during carotid endarterectomy. Temporary intraoperative shunt occlusions are instantly indicated by accurate ocular pulse delay information digitally displayed to the surgeon. Corrections in shunt placement may be made promptly and, therefore, adequate internal carotid blood flow maintained, allowing "safe" time for careful endarterectomy or vascular reconstruction. Verification of satisfactory flow after arteriorhaphy is obtained by oculoplethysmography.

Carotid Artery Thrombosis↗

Dose-dependent effects of milk lipids on sex hormone and blood lipid levels in male mice.

Diets containing powdered whole milk caused a dose dependent increase in seminal vesicle weights when fed to 21 day old intact male mice. Blood cholesterol levels increased as the lipids in the diet increased. Triglyceride levels were high and inversely related to lipid intake. Peripheral androgen concentrations decreased as the lipid intake and seminal vesicle weights increased, indicating a possible shift of the hormone to the target organ tissue.

Administration, Oral↗