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Biomedical subjects

J H Adams

Publications and source records attributed to J H Adams.

At least 19 recordsLinked to original sources
PubMed2000

Spatial and temporal dynamics of the secretory pathway during differentiation of the Plasmodium yoelii schizont.

A specialized complex of apical organelles facilitates Plasmodium merozoite invasion into the erythrocyte. Even though the apical organelles are crucial to the invasion process, relatively little is known about how they function or their biosynthesis during asexual replication. MAEBL is an erythrocyte binding protein located in the rhoptries and on the surface of mature merozoites and is expressed at the beginning of schizogony before the first nuclear division. Therefore, we have characterized MAEBL as a marker for the biosynthetic pathway of the rhoptry apical organelle during the final phase of intraerythrocytic development and as a marker for the nascent rhoptry vesicle in the immature schizont. An extensive proliferation of the endoplasmic reticulum occurred at the onset of schizogony and was seen as a complex but transient tubule array near the parasite surface. Both the rhoptry protein MAEBL and surface protein MSP-1 appeared to be present in this tubular reticular network together with endoplasmic reticulum markers. MAEBL then transits through Golgi bodies positioned near the parasite plasma membrane, directly adjacent to the network. Rhoptry organelle precursors are seen at the three to four nuclei stage of schizont development, remaining near the plasma membrane throughout schizogony. These studies constitute the first direct evidence that proteins of the rhoptry organelles transit through compartments of the 'classical' secretory pathway.

Animals↗
PubMed2000

The neuropathology of the vegetative state after an acute brain insult.

The vegetative state is often described clinically as loss of function of the cortex while the function of the brainstem is preserved. In an attempt to define the structural basis of the vegetative state we have undertaken a detailed neuropathological study of the brains of 49 patients who remained vegetative until death, 1 month to 8 years after an acute brain insult. Of these, 35 had sustained a blunt head injury and 14 some type of acute non-traumatic brain damage. In the traumatic cases the commonest structural abnormalities identified were grades 2 and 3 diffuse axonal injury (25 cases, 71%). The thalamus was abnormal in 28 cases (80%), and in 96% of the cases who survived for more than 3 months. Other abnormalities included ischaemic damage in the neocortex (13 cases, 37%) and intracranial haematoma (nine cases, 26%). In the non-traumatic cases there was diffuse ischaemic damage in the neocortex in nine cases (64%) and focal damage in four (29%); the thalamus was abnormal in every case. There were cases in both groups where the cerebral cortex, the cerebellum and the brainstem were of structurally normal appearance. In every case, however, there was profound damage to the subcortical white matter or to the major relay nuclei of the thalamus, or both. These lesions render any structurally intact cortex unable to function because connections between different cortical areas via the thalamic nuclei are no longer functional, and there is also extensive damage to afferent and efferent cerebral connections.

Adolescent↗
PubMed2000

Naturally acquired and vaccine-elicited antibodies block erythrocyte cytoadherence of the Plasmodium vivax Duffy binding protein.

Malaria merozoites require the presence of specific surface receptors on the red blood cell for invasion. Plasmodium vivax, requires the Duffy blood group antigen as an obligate receptor for invasion. The parasite Duffy binding protein (DBP) is the ligand involved in this process, making the DBP a potential vaccine candidate. A preliminary objective was to study whether people exposed to vivax malaria acquire antibodies that have the ability to block erythrocyte cytoadherence to the PvDBP. In comparison, we studied the immunogenicity of various recombinant DBP vaccines and investigated their potential to induct antifunctional antibodies. In order to do so, recombinant proteins to different regions of the putative ectodomain of the DBP and a DNA vaccine were used to immunize laboratory animals. An in vitro cytoadherence assay was used to investigate the presence of antifunctional antibodies in plasmas from people naturally exposed to vivax malaria, as well as in antisera obtained by animal vaccination. Our results showed that human plasma from populations naturally exposed to vivax malaria, as well as antisera obtained by vaccination using recombinant proteins, a DNA vaccine, and a synthetic peptide to DBP, inhibited in vitro binding of human erythrocytes to the DBP ligand domain (DBP(II)) in correlation to their previously measured antibody titer. Our results provide further evidence for the vaccine potential of this essential parasite adhesion molecule.

Animals↗
PubMed1999

The relationship among John Henryism, hostility, perceived stress, social support, and blood pressure in African-American college students.

African Americans' rates of hypertension-related morbidity and mortality are several times that of white Americans. A number of behavioral and psychological variables may influence these differences. John Henryism, characterized by active coping to overcome obstacles, is one such variable. Prior research indicates that among highly educated individuals, high levels of John Henryism may be associated with decreased hypertension risk. The purpose of this study was to identify a cohort of well-educated African Americans to establish a baseline examination of the relationships between John Henryism, hostility, perceived stress, social support and resting systolic and diastolic blood pressures (SBP and DBP, respectively). Participants completed measures of study variables and resting blood pressures were taken. Results indicated that high family and friendship support were related to reports of lowered levels of stress (P<.001). Family support was associated with decreased risk for elevated DBP (P<.05). A positive association between hostility and DBP was found (P<.01). Perceived stress was negatively associated with SBP (P<.05), but did not have an independent effect on DBP. Similarly, no interactive effects of John Henryism and perceived stress were found on blood pressure. Examination of this cohort over time will reveal the impact of John Henryism and other variables on blood pressure elevations and hypertension.

Adaptation, Psychological↗
PubMed1998

Plasmodium yoelii YM MAEBL protein is coexpressed and colocalizes with rhoptry proteins.

We have previously cloned genes from multiple rodent malaria species exhibiting characteristics of the genes encoding Duffy binding like-erythrocyte binding proteins (DBL-EBP). Homology is seen in the intron/exon structure of the genes and in the carboxyl terminal region (including the deduced carboxyl cysteine-rich domain) of the proteins they encode. However, the amino termini of these proteins are not homologous to the DBL-EBP but contain tandem cysteine-rich regions that are similar to the cysteine-rich region of AMA-1 (apical membrane antigen-1), a rhoptry protein. This new family of proteins has been termed MAEBL and these are paralogues of both AMA-1 and the DBL-EBP. Serum against the carboxyl cysteine-rich region of the Plasmodium yoelii YM MAEBL reacted to parasites with a punctate fluorescence pattern characteristic of apical organelle proteins and also localized MAEBL to the surface of merozoites within schizonts. This antiserum immunoprecipitated a protein doublet (120/128 kDa) that was unexpectedly insoluble when compared to members of the DBL-EBP. Characterization of MAEBL was extended through colocalization studies comparing the P. yoelii YM MAEBL to other parasite proteins. This protein appeared to be located in the rhoptry organelles as it colocalized with both AMA-1 and the P. yoelii 235 kDa rhoptry proteins within parasites. In addition, MAEBL is expressed relatively early in schizont development and appears on the merozoite surface after segmentation. Both the pattern and time of expression of the P. yoelii YM MAEBL are consistent with a rhoptry rather than a microneme protein.

Animals↗
PubMed1998

Miranda mediates asymmetric protein and RNA localization in the developing nervous system.

Neuroblasts undergo asymmetric stem cell divisions to generate a series of ganglion mother cells (GMCs). During these divisions, the cell fate determinant Prospero is asymmetrically partitioned to the GMC by Miranda protein, which tethers it to the basal cortex of the dividing neuroblast. Interestingly, prospero mRNA is similarly segregated by the dsRNA binding protein, Staufen. Here we show that Staufen interacts in vivo with a segment of the prospero 3' UTR. Staufen protein and prospero RNA colocalize to the apical side of the neuroblast at interphase, but move to the basal side during prophase. Both the apical and basal localization of Staufen are abolished by the removal of a conserved domain from the carboxyl terminus of the protein, which interacts in a yeast two-hybrid screen with Miranda protein. Furthermore, Miranda colocalizes with Staufen protein and prospero mRNA during neuroblast divisions, and neither Staufen nor prospero RNA are localized in miranda mutants. Thus Miranda, which localizes Prospero protein, also localizes prospero RNA through its interaction with Staufen protein.

Animals↗
PubMed1998

A family of chimeric erythrocyte binding proteins of malaria parasites.

Proteins sequestered within organelles of the apical complex of malaria merozoites are involved in erythrocyte invasion, but few of these proteins and their interaction with the host erythrocyte have been characterized. In this report we describe MAEBL, a family of erythrocyte binding proteins identified in the rodent malaria parasites Plasmodium yoelii yoelii and Plasmodium berghei. MAEBL has a chimeric character, uniting domains from two distinct apical organelle protein families within one protein. MAEBL has a molecular structure homologous to the Duffy binding-like family of erythrocyte binding proteins located in the micronemes of merozoites. However, the amino cysteine-rich domain of MAEBL has no similarity to the consensus Duffy binding-like amino cysteine-rich ligand domain, but instead is similar to the 44-kDa ectodomain fragment of the apical membrane antigen 1 (AMA-1) rhoptry protein family. MAEBL has a tandem duplication of this AMA-1-like domain, and both of these cysteine-rich domains bound erythrocytes when expressed in vitro. Differential transcription and splicing of the maebl locus occurred in the YM clone of P. yoelii yoelii. The apical distribution of MAEBL suggested localization within the rhoptry organelles of the apical complex. We propose that MAEBL is a member of a highly conserved family of erythrocyte binding proteins of Plasmodium involved in host cell invasion.

Amino Acid Sequence↗
PubMed1998

Cholesterol concentrations and cardiovascular reactivity to stress in African American college volunteers.

Cholesterol levels and cardiovascular responses to emotionally arousing stimuli were examined in 60 healthy African American males and females. Cardiac output, stroke volume, contractile force, heart rate, and blood pressure were measured as the participants viewed two racially noxious scenes on videotape. Total serum cholesterol, high-density lipoproteins (HDL), low-density lipoproteins (LDL), and triglycerides were measured within 2 weeks of viewing the scenes. Multiple regression analysis showed that LDL and HDL were significant predictors of blood pressure responses. A correlation analysis revealed that total serum cholesterol and LDL were positively correlated with stroke volume, contractile force, and blood pressure reactivity. A possible relationship among stress, beta-adrenergic activity, and nonmetabolized free fatty acids is discussed. These findings suggest that cardiovascular reactivity to stress may be a new risk factor for heart and vascular diseases.

Adolescent↗
PubMed1998

Serologic responses to recombinant Plasmodium vivax Duffy binding protein in a Colombian village.

The Plasmodium vivax Duffy binding protein (DBP) is essential during merozoite invasion into human erythrocytes. Because of its biological importance, the DBP is also seen to have potential use as a malaria blood-stage vaccine. We have used a soluble recombinant DBP (rDBP) containing the functional ligand domain to assess the natural immunogenicity of DBP in a low-endemic vivax malaria region. Human sera from adult residents from a Colombian village with unstable vivax malaria transmission reacted specifically with the rDBP as determined by ELISA. There was a significant positive correlation between increased antibody response (average, median, and percent positives) and age of patients, although the level of responses did vary considerably in their reactivity to the rDBP from negative to very high level within each age group. These data confirm previous findings on the serologic reactivity of the DBP in exposed populations and that immunologic boosting to the DBP occurs in malaria-endemic regions even with low-level transmission.

Adolescent↗
PubMed1997

Erythrocyte binding protein homologues of rodent malaria parasites.

Erythrocyte invasion by malaria parasites requires specific molecular interactions between the merozoite and erythrocyte surface receptors. A well-conserved, functionally important family of erythrocyte binding proteins is the EBP family. The EBP family includes the Plasmodium vivax, P. knowlesi Duffy binding protein (DBP) family and the P. falciparum erythrocyte binding antigen-175 (EBA-175). The EBP are transmembrane proteins, characterized by two conserved cysteine-rich domains, expressed in the micronemes of invasive merozoites. Oligonucleotide primers matching the region encoding the carboxyl cysteine-rich domain of the EBA-175 were used in a polymerase chain reaction to identify homologous genes in P. berghei and P. yoelii yoelii, leading to the isolation of a P. berghei partial genomic clone. This clone contained a 323 bp region that had high deduced amino acid sequence similarity to the amino acid sequences of the carboxyl cysteine-rich domains of the DBP family and EBA-175. The P. berghei carboxyl cysteine-rich domain was followed by a putative transmembrane domain and a cytoplasmic domain, demonstrating an exon-intron structure at the 3' end homologous to P. vivax dbp and P. falciparum eba-175. The carboxyl cysteine-rich domain is also highly conserved among P. berghei, P. y. yoelii, P. chabaudi and P. vinckei and is encoded by a single copy gene. Antisera prepared against the carboxyl cysteine-rich domain of the rodent malaria EBP homologues reacted with a 120 and 128 kDa protein doublet on Western blots of P. berghei parasite antigen and showed an apical localization pattern within merozoites by indirect immunofluorescence assays.

Amino Acid Sequence↗
PubMed1997

Expression and serologic activity of a soluble recombinant Plasmodium vivax Duffy binding protein.

Plasmodium vivax Duffy binding protein (DBP) is a conserved functionally important protein. P. vivax DBP is an asexual blood-stage malaria vaccine candidate because adhesion of P. vivax DBP to its erythrocyte receptor is essential for the parasite to continue development in human blood. We developed a soluble recombinant protein of P. vivax DBP (rDBP) and examined serologic activity to it in residents of a region of high endemicity. This soluble rDBP product contained the cysteine-rich ligand domain and most of the contiguous proline-rich hydrophilic region. rDBP was expressed as a glutathione S-transferase (GST) fusion protein and was isolated from GST by thrombin treatment of the purified fusion protein bound on glutathione agarose beads. P. vivax rDBP was immunogenic in rabbits and induced antibodies that reacted with P. vivax and Plasmodium knowlesi merozoites. Human sera from adult residents of a region of Papua New Guinea where malaria is highly endemic or P. vivax-infected North American residents reacted with rDBP in an immunoblot and an enzyme-linked immunosorbent assay. The reactivity to reduced, denatured P. vivax rDBP and the cross-reactivity with P. knowlesi indicated the presence of immunogenic conserved linear B-cell epitopes. A more extensive serologic survey of Papua New Guinea residents showed that antibody response to P. vivax DBP is common and increases with age, suggesting a possible boosting of the antibody response in some by repeated exposure to P. vivax. A positive humoral response to P. vivax DBP correlated with a significantly higher response to P. vivax MSP-1(19). The natural immunogenicity of this DBP should strengthen its usefulness as a vaccine.

Adolescent↗
PubMed1996

Plasmodium vivax: favored gene frequencies of the merozoite surface protein-1 and the multiplicity of infection in a malaria endemic region.

In this study, we present an analysis of the Plasmodium vivax MSP-1 polymorphic region 5 and identify a new recombinant gene element. In clinical isolates from Papua New Guinea (PNG), the P. vivax MSP-1 gene type was characterized by restriction fragment length polymorphisms and by Southern blot oligonucleotide hybridizations using probes to type-specific sequences. There were three pairs of dimorphic gene elements in the MSP-1 polymorphic region 5; four of the eight potential different combinations of sequence elements for this region have been identified. The center gene segment was the most polymorphic, especially for the glutamine (Q) repeat element with virtually every gene containing a different length of Q repeats, a finding consistent with database sequence information. The frequencies of all of the polymorphic MSP-1 gene elements were approximately equal except for the first segment, which was biased 10:1 for the Type II (Sal-1 type) versus Type I (Belem type) gene segment. In fact, only one combination (I/Q/S) of the genetic elements containing the type I gene segment for polymorphic region 5 was identified, a finding consistent with sequences reported to gene data banks. Considering only the multiplicity of MSP-1 gene types, 38% of the patients were identified as having multiple infections; when correlated with the circumsporozoite protein and the Duffy antigen binding protein gene types, the multiple infection rate increased to 65% of 23 isolates characterized. Increased age was the only clinical parameter that positively correlated with multiclonal infections and there was no other apparent bias or linkage of gene types among the three loci. These data identify multiple clonal populations of P. vivax in the PNG population and potentially a high rate of concurrent infections in clinical cases. The extreme polymorphism of the MSP-1 polymorphic region 5 suggests that frequent recombination occurs within this gene. The bias in frequency for one recombinant gene motif indicates that intrinsic host or parasite factors may engender increased frequency of one genetic element over another. Failure to identify this type of discrete clonal marker as well as reliance on a single marker can mask the true multiclonal nature of an infection and lead to underestimation of the multiplicity of infection.

Amino Acid Sequence↗
PubMed1995

Axonal injury: a universal consequence of fatal closed head injury?

beta-Amyloid precursor protein immunostaining has recently been shown to be a reliable method for detecting the damage to axons associated with fatal head injury. In an attempt to compare the efficacy of this technique with conventional histological detection of axonal damage, we have reanalysed sections from a large well-characterised series of head-injured and control patients. The results indicate that the frequency of axonal injury has been vastly underestimated using conventional silver techniques, and that axonal injury may in fact be an almost universal consequence of fatal head injury.

Adolescent↗
PubMed1995

The nature, distribution and causes of traumatic brain injury.

The identification and interpretation of brain damage resulting from a non-missile head injury is often not easy with the result that the most obvious structural damage identified postmortem may not be the most important in trying to establish clinicopathological correlations. For example patients with a fracture of the skull, quite severe cerebral contusions or a large intracranial haematoma that is successfully treated can make an uneventful and complete recovery if no other types of brain damage are present. However, not infrequently more subtle forms of pathology are present and ones that can only be identified microscopically. A systematic and pragmatic approach through the autopsy is therefore required and one that recognises the need for tissue to be retained in ways that are appropriate for cellular and molecular studies.

Apolipoproteins E↗
PubMed1994

Dimorphism and intergenic recombination within the microneme protein (MP-1) gene family of Plasmodium knowlesi.

The microneme protein-1 (MP-1) of Plasmodium knowlesi and Plasmodium vivax facilitates merozoite invasion of the erythrocyte by binding to Duffy blood group antigens. Since this protein is important in the invasion process and is a potential vaccine candidate, it is important to understand the nature of diversity within the MP-1 gene. Nine MP-1 gene sequences were compared from 2 isolates of P. knowlesi and a laboratory strain of P. vivax. The MP-1 genes of P. knowlesi were dimorphic based upon the central hydrophilic regions (III and IV) that were well conserved as alpha and beta types. Other regions were conserved among all P. knowlesi genes except for the amino cysteine-rich region (region II), a region predicted to be the initial contact site of the erythrocyte binding domain. Two distinct sequence motifs and part of a third were identified in region II that had a common identity of 68%. In some MP-1 genes recombination had occurred to create hybrids of the two sequence types. All cysteines and aromatic amino acids of region II were conserved in all genes or within a sequence type. There were 2 apparent recombination points within region II where switching occurred between sequence types. Another possible recombination site, identified as a common sequence motif, was identified in the middle of the hydrophilic region, at the beginning of regions III or IV. Nonsynonymous mutations within region II were biased towards radical amino acid changes, especially towards the carboxyl third, where there were 3 distinct types of sequence. Most synonymous and nonsynonymous nucleotide mutations within regions I, V, and VI were infrequent, individual events and not associated with any particular sequence type. Cysteine-rich regions of the P. vivax MP-1 gene compared to the P. knowlesi genes were characterized by an increased number of synonymous and nonsynonymous changes. This data identifies 2 mechanisms for generation of diversity in the MP-1 gene family, intergenic recombination and nucleotide mutations. Both may be mechanisms the parasite uses to evade the host immune response or to alter erythrocyte receptor specificity.

Amino Acid Sequence↗