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Biomedical subjects

A Morgan

Publications and source records attributed to A Morgan.

At least 145 records · Page 8Linked to original sources
PubMed1993

Femoral nerve palsy following laparoscopic inguinal herniorrhaphy.

Laparoscopic inguinal herniorrhaphy has undergone a rapid evolution. The technique currently favored by many laparoscopic surgeons places a prosthetic mesh over the myopectineal orifice. We describe a femoral nerve palsy after such an operation and detail the anatomy of the nerves at risk during laparoscopic inguinal herniorrhaphy. We discuss how injury to these structures and the attendant anterior thigh pain and weakness may be avoided.

Adult↗
PubMed1993

Identification of human T cell epitopes in the Mycobacterium leprae heat shock protein 70-kD antigen.

In a number of pathogens, heat shock proteins (hsp) stimulate humoral and cellular immune responses despite significant sequence identity with host hsp. The 70-kD hsp of Mycobacterium leprae, which shares 47% identity with human hsp70 at the protein level, elicited a T cell response in most Myco. bovis (bacille Calmette-Guérin (BCG)) vaccinees as well as leprosy and tuberculosis patients and their contacts. In order to locate T cell epitopes, DNA fragments encoding portions of the 70-kD hsp were expressed in the vector pGEX-2T and tested for T cell reactivity in an in vitro proliferative assay. Cultures of peripheral blood mononuclear cells (PBMC) from BCG vaccinees indicated that the C-terminal half of the molecule contained multiple T cell epitopes, as the T cells from a majority of Myco. leprae hsp70-reactive individuals responded to C-344. Lower proportions of patients with paucibacillary leprosy (36%) and tuberculosis patients (16%) responded to C-344. The smaller C-142 fragment which includes the terminal 70 residues unique to Myco. leprae and is the target for the human antibody response elicited a cellular response in few patients and no vaccinees. In order to map T cell epitopes, two series of synthetic peptides encompassing the region 278-502 were prepared. Using overlapping 12mer and 20mer peptides, this region of the molecule was found to contain several potential T cell epitopes. The longer peptides gave a clearer indication of reactive sequences including regions of the molecule which were not identified with the 12mer peptides. Fine mapping of reactive peptide pools using the 12mer peptides identified two T cell epitopes. Although both were located in regions of the molecule shared with Myco. tuberculosis, one appeared to be cross-reactive with the equivalent human sequence, and thus has the potential to initiate autoimmune responses.

Amino Acid Sequence↗
PubMed1993

Photosensitization with etiobenzochlorins and octaethylbenzochlorins.

The photophysical and photobiological properties of a series of etiobenzochlorins were evaluated in cell culture using murine leukemia L1210 cells. In the series of agents tested, the chlorin-(mono)sulfonate was the most efficacious, the tin chlorin somewhat less so and the tin chlorin-sulfonate much less active. The parent chlorin was essentially inactive at the limit of solubility. Photodamage was assessed by measuring alterations in surface hydrophobicity (via a two-phase partitioning procedure), amino acid transport and membrane potential. Additional information was provided from fluorescence microscopy, which was used to identify sites of sensitizer binding and effects of photodamage on the binding patterns of fluorescent probes specific for mitochondria, lysosomes and plasma membranes. Effects of photodamage on fluorescence lifetime distribution of the membrane probe trimethylaminodiphenyl hexatriene were examined. The data obtained were consistent with localization of the parnet etiobenzochlorin and tin derivative at lysosomal loci, the chlorin-sulfonate at plasma and mitochondrial membranes and tin-sulfonate at the cell surface.

Animals↗
PubMed1993

Trauma-related symptoms in veterans of Operation Desert Storm: a preliminary report.

OBJECTIVE: This study was designed to examine prospectively the development of trauma-related symptoms over time in two reserve units of Operation Desert Storm veterans. METHOD: One month and 6 months after returning from the Persian Gulf area, 84 National Guard reservists, from one medical unit and one military police unit, completed questionnaires on their exposure to combat and to specific stressors and rated the severity of their symptoms of posttraumatic stress disorder (PTSD) on two different scales. Differences in symptom severity at the two time points were analyzed. RESULTS: Scores on the Mississippi Scale for Combat-Related Post-Traumatic Stress Disorder, but not severity ratings on a symptom scale based on DSM-III-R PTSD criteria, increased significantly from the 1-month to the 6-month rating time. At both time points, symptoms of hyperarousal were more severe than symptoms of reexperiencing or avoiding trauma-related events. Level of exposure to combat, as reflected by the Combat Exposure Scale and a Desert Storm trauma questionnaire, was significantly associated with score on the Mississippi PTSD scale. There were no significant differences in combat exposure and PTSD symptoms between the male and female subjects or between the medical and police units. CONCLUSIONS: These preliminary findings suggest that a high percentage of Desert Storm veterans experienced some trauma-related symptoms after returning to the United States. Six months after the war, these symptoms, although relatively mild, had not significantly improved in this study group as a whole. For research on longer-term outcome, follow-up of these 84 reservists continues.

Combat Disorders↗
PubMed1993

Expression and relationships of seven public idiotypes of DNA-binding autoantibodies on monoclonal antibodies and serum immunoglobulins.

Many studies have shown that DNA-reactive autoantibodies share cross-reactive public idiotypes that are defined, usually, by single anti-idiotype reagents. Because anti-idiotype antibodies or antisera will be limited in their ability to detect all the idiotopes of a particular antibody, their use will tend to underestimate the full extent of idiotype sharing between different antibodies. In order to define more comprehensively the extent of idiotype sharing in DNA autoantibodies, a panel of DNA-binding monoclonal autoantibodies from lupus mice was examined with a range of anti-idiotype antisera prepared in rabbits (five sera), guinea pigs (four sera) and a sheep. Each idiotype was detected on more antibodies than its original reference monoclonal antibody, and idiotopes of each were also present on serum immunoglobulins from lupus mice. Of 23 monoclonal antibodies 65% reacted with one or more of the anti-idiotype reagents. On these criteria, all the idiotypes were public; none was private in its expression. In about half the cases the idiotypes were located in or near the antigen-binding sites of the antibodies, but a direct relationship to specificity was not obvious except in the case of Id.228 present on antibodies with a relatively high affinity for single-stranded DNA. In other cases there was no obvious relationship between idiotype and specificity. Antibodies from the same mouse did not each express the same array of idiotopes.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1993

Spatial localization of agonist-induced Ca2+ entry in bovine adrenal chromaffin cells. Different patterns induced by histamine and angiotensin II, and relationship to catecholamine release.

The spatial organization of agonist-induced Ca2+ entry in single bovine adrenal chromaffin cells has been investigated using video-imaging techniques to visualize fura-2 quenching by the Ca2+ surrogate, Mn2+. The potent secretagogue histamine, in addition to releasing Ca2+ from intracellular stores, resulted in a large influx of external Mn2+ that occurred over the entire surface of the cell. The influx of Ca2+ that this mirrors was found to be an obligatory requirement for the triggering of catecholamine release by histamine, which suggests that such a global influx of Ca2+ into the cell probably underlies the ability of this agonist to stimulate a large secretory response. By contrast, the weaker secretagogue angiotensin II, which also acts through the second messenger inositol trisphosphate, produced a localized entry of external Mn2+ in 64% of cells. In these cells, localized Mn2+ entry always occurred at the pole of the cell in which the angiotensin II-induced rise in [Ca2+]i was largest. Since exocytosis in response to angiotensin II has previously been shown to be restricted to this same pole of the cell (Cheek et al. (1989). J. Cell Biol. 109, 1219-1227), these results suggest that localized influx of Ca2+ in response to angiotensin II could underlie the polarized exocytotic response observed with this stimulus. These results directly demonstrate that different agonists can induce different patterns of divalent cation influx in the same cells and, furthermore, suggest how these different patterns can have a direct influence on cellular function.

Adrenal Medulla↗
PubMed1993

Has social psychiatry met its Waterloo? Methodological and ethical issues in a community study.

The first wave of a longitudinal and prospective community study of minor psychiatric disorder among a cohort of socially disadvantaged women has been completed. The study hopes to extend the social model of depression, as initially proposed by Brown and Harris [1], by examining the mediating effects of personality factors and social support. Findings from previous studies have been largely restricted to associations between variables which may be at least partly attributable to methodological limitations in design and measurement techniques: specifically, the use of inherently biased sampling methods, single interview, retrospective data collection and less standardized diagnostic criteria to determine caseness. This paper discusses design strategies which were adopted to reduce the confounding between variables resulting from these limitations. The effectiveness of these strategies is evaluated in light of some methodological and ethical issues which have arisen during the recruitment of participants and the first wave of data collection.

Adult↗
PubMed1993

Exocytosis in adrenal chromaffin cells.

Recent advances have led to an increased understanding of the Ca(2+)-signalling pathway leading to exocytosis in bovine adrenal chromaffin cells. Video-imaging studies have allowed the temporal and spatial aspects of the Ca2+ signal to be investigated in detail. Ca2+ entry at the plasma membrane appears to be crucial for the activation of exocytosis. Ca2+ can enter through the nicotinic channel or characterised voltage-activated channels, or through other poorly defined pathways due to a variety of agonists. Emptying of internal Ca2+ stores is sufficient to activate a Ca2+ entry pathway. The elevation of cytosolic Ca2+ concentration leads to a reorganisation of the cortical actin network and to the triggering of exocytosis. Studies on permeabilised chromaffin cells have resulted in the identification of some of the proteins that control Ca(2+)-dependent exocytosis. These include the peripheral plasma membrane protein annexin II and the cytosolic proteins, protein kinase C and 14-3-3 proteins (Exo1).

Actins↗
PubMed1992

Interaction between protein kinase C and Exo1 (14-3-3 protein) and its relevance to exocytosis in permeabilized adrenal chromaffin cells.

The roles of protein kinase C (PKC) and Exo1 in exocytosis from digitonin-permeabilized adrenal chromaffin cells were explored by using exogenous purified proteins in a run-down/reconstitution system. The stimulatory action of Exo1 on exocytosis from run-down cells was found to be completely dependent on the continuous presence of exogenous MgATP, suggesting that it acts on the slow phase of exocytosis [Holz, Bittner, Peppers, Senter & Eberhard (1989), J. Biol. Chem. 264, 5412-5419]. Partially purified rat brain PKC was found to be able to stimulate Ca(2+)-dependent exocytosis from run-down cells in a dose-dependent manner. This effect was indeed due to PKC and not a contaminant in the PKC fraction, since the PKC activator phorbol 12-myristate 13-acetate (PMA), under conditions in which control secretion was not affected, potentiated the effect of the exogenous PKC in stimulating secretion. Furthermore, although either PKC or Exo1 alone could stimulate exocytosis from run-down cells, the effect of combining the fractions was synergistic, as had previously been observed using PMA treatment combined with Exo1 incubation [Morgan & Burgoyne (1992) Nature (London) 355, 833-836]. The observed synergy between PKC and Exo1 was not due to PKC-mediated phosphorylation of Exo1, and Exo1 was found not to affect PKC activity in enzyme assays. We conclude that PKC and Exo1 act synergistically in the slow phase of Ca(2+)-dependent exocytosis from adrenal chromaffin cells. Furthermore, PKC does not directly affect Exo1, but rather enhances the activity of Exo1 by a putative phosphorylation of another, unidentified, component of the exocytotic machinery which facilitates the action of Exo1 in exocytosis.

14-3-3 Proteins↗
PubMed1992

Exo1 and Exo2 proteins stimulate calcium-dependent exocytosis in permeabilized adrenal chromaffin cells.

In many cell types an increase in cytosolic calcium is the main signal for the exocytotic release of stored secretory components such as hormones and neurotransmitters. The site of action of calcium in exocytosis is not known, neither are the participating molecules. In the case of the intracellular membrane fusions that occur during transport through early stages of the secretory pathway, several cytosolic and peripheral membrane proteins are necessary. Permeabilized cells have been useful in understanding the requirements for calcium and nucleotides in regulated exocytosis and under certain conditions there is leakage of soluble protein components and run-down of the exocytotic response. This system can be used to identify the soluble proteins involved in exocytosis, one candidate in chromaffin cells being annexin II (calpactin). Here we use this assay to identify two other cytosolic protein factors that regulate exocytosis in permeabilized adrenal chromaffin cells, which we term Exo1 and Exo2. Exo1 from brain cytosol resolves on electrophoresis in SDS-polyacrylamide gels as a group of polypeptides of relative molecular mass approximately 30,000 and shares sequence homology with the 14-3-3 family of proteins. The ability of Exo1 to reactivate exocytosis is potentiated by protein kinase C activation and therefore Exo1 may influence the protein kinase C-mediated control of Ca(2+)-dependent exocytosis.

14-3-3 Proteins↗
PubMed1992

Transcriptional expression of the viral genome in the Epstein-Barr virus-induced tamarin lymphoma and the corresponding lymphoblastoid tumour lines.

Inoculation of the cottontop tamarin with Epstein-Barr virus (EBV) invariably gives rise to mono- or oligoclonal large cell lymphoma occurring at multiple sites, and which resembles to a certain extent B cell lymphoma that occurs in the immunodeficient patient. The viral transcriptional pattern in tamarin tumour biopsies and in the corresponding tumour cell lines was investigated by means of the synthesis of radioactive single-stranded cDNA. It was found that the EBV transcripts came mainly from the fragments BamH1-H, BamH1-S, BamH1-A and EcoR1-Dhet. Transcripts from a few other early or late genes, namely BARF1, BSLF1/BMLF1, BBLF-4, BLLF1 and BXLF2, were also detected in one of the three biopsies tested. It would be important to characterize the transcripts that originate from the region where viral latent expression has not previously been observed. Our results also revealed that there is a sharp increase in EBV transcription in the tumour cell lines derived from the tamarin lymphomas. Simultaneously, the copy number of the viral genome was found to be amplified. Such a significant change in viral activity might be indicative of a close virus-host cell interaction in vivo.

Animals↗
PubMed1992

Estimates of embryonic and fetal doses from 239Pu.

Previously reported studies on the transfer of 238Pu from the maternal circulation to the developing embryo and fetus in rats and guinea pigs have provided data for developing dosimetric models. The highest concentrations of 238Pu were measured in the yolk sac. In late gestation, preferential uptake of 238Pu in liver and bone was observed. The data obtained, together with other published information, have been used to estimate in utero doses to hemopoietic tissues, taking account of transfer to the blastocyst/egg cylinder, yolk sac, liver, and bone marrow. From animal data, the concentration ratios relative to maternal liver for these tissues were taken to be 0.1, 2, 0.01, and 0.02, respectively, and were applied to periods of human gestation of 0-2.5 wk, 2.5-6 wk, 6-12 wk, and 12-38 wk, respectively. Doses to fetal tissues from 239Pu were calculated for chronic ingestion by the mother for a total of 1.8 kBq 239Pu during the year of pregnancy, giving a committed effective dose to the mother of 1 mSv. On this basis, the total in utero dose to hemopoietic tissue was about 2 microSv compared with red bone marrow doses of 34 microSv to the mother for the year. The yolk sac and bone marrow dominated in utero doses. The total dose to hemopoietic tissue in the offspring to age 70 y, taking into account the activity present at birth and including in utero doses, was estimated as 24 microSv compared with a maternal dose to red bone marrow of 2.5 mSv. An acute maternal intake of 1.8 kBq by ingestion during the period of yolk sac hemopoiesis would result in the highest in utero dose, estimated at about 36 microSv. However, activity at birth would be lower, giving only a small additional dose.

Animals↗
PubMed1992

Effects of inhaled alpha-emitting actinides on mouse alveolar macrophages.

The effects of inhaled alpha-emitting actinides on the alveolar macrophage (AM) population of the rodent lung are reviewed and, in particular, of the effects of 239PuO2 on murine AM. The effects discussed include changes the AM pool size, macrophage diameter, mobility, phagocytic competence, and enzyme content. Finally, similarities in the dose-response relationships for the induction of nuclear aberrations by alpha emitters and in the induction of lung tumors by the same materials are noted.

Actinoid Series Elements↗
PubMed1991

Surgical treatment and long-term neurodevelopmental outcome for infants with idiopathic aqueductal stenosis.

Evaluation of in utero shunting for fetal ventriculomegaly requires an analysis of the ex utero treatment of a comparison population of infants with idiopathic aqueductal stenosis (IAS). In this study, 14 neonates with IAS were followed with detailed developmental assessment profiles for 18 months or longer. Using magnetic resonance imaging, the preoperative and postoperative frontal cortical mantle widths (FCMW) were determined for each patient. Four of 14 children demonstrated normal outcomes while 5 of 14 children showed abnormal outcomes. The remaining 5 children demonstrated minimally impaired outcomes. No child with a postoperative FCMW below 30 mm showed normal development on any scale, while all children with abnormal development demonstrated a postoperative FCMW of 21 mm or less. In conclusion, the prognosis for normal long-term neurodevelopment in infants with IAS, despite prompt ex utero treatment, is guarded; the majority of such children will show developmental delays of varying degrees. The FCMW serves as a reasonable prognostic indicator in this patient population.

Cerebral Aqueduct↗
PubMed1991

A role for DNA in anti-DNA antibodies binding to endothelial cells.

Vascular injury and microvascular thrombosis are prominent features of systemic lupus erythematosus, as are circulating DNA-binding antibodies (DNAb). Experimental glomerulonephritis can be induced by anti-endothelial cell antibodies, and polyreactive DNAb might be pathogenetic by binding to endothelial cells, perhaps influencing their non-thrombogenic nature. To test this hypothesis, eight monoclonal antibodies (mAb) that bind to DNA derived from (NZB x NZW)F1 or MRL/Mp-lpr/lpr mice, were tested for their ability to bind to human umbilical vein endothelial cells (HUVEC). Binding was assessed using flow cytometry, fluorescence microscopy and cellular ELISA. Three of the eight mAb, at concentrations employed in this study, bound to HUVEC and dermal fibroblasts. Of these three mAb, one bound also to platelets. Two of the three demonstrated strong binding to (1) freshly isolated, collagenase-digested HUVEC, (2) 2nd passage HUVEC in suspension after trypsinization and, (3) 2nd passage HUVEC growing on plastic plates. To determine whether DNA itself acted as a ligand in this binding, prior treatment with DNAase was studied. Treatment of the endothelial cells with DNAase had no effect on the binding of one mAb, but DNAase treatment of this monoclonal itself resulted in a 60% reduction in binding to HUVEC, suggesting that the binding might be mediated through DNA in the form of a DNA/anti-DNA immune complex. In contrast, DNAase digestion of the endothelial cells caused a 40% reduction in the binding of the other two monoclonal antibodies. Furthermore, one of the two mAb bound 30% more to HUVEC after themselves being subjected to DNAase treatment. These two monoclonals may therefore be binding directly to HUVEC, possibly to DNA associated with the membrane. Prior DNAase digestion of dermal fibroblasts had a more profound effect on the binding of all three autoantibodies compared to HUVEC after similar treatment. Therefore, DNA can bind independently to either antibody or cell, thus supporting build up of complexes and capture of preformed complexes. Functionally, the binding of mAb to HUVEC did not influence thrombin-induced prostacyclin synthesis, in contrast to a control monoclonal anti-endothelial cell antibody EN4, which did.

Animals↗