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Biomedical subjects

M Elmore

Publications and source records attributed to M Elmore.

14 recordsLinked to original sources
PubMed2000

Cloning, expression and evaluation of a recombinant sub-unit vaccine against Clostridium botulinum type F toxin.

A synthetic gene encoding the Hc (binding) domain of Clostridium botulinum neurotoxin F (FHc) was expressed in Escherichia coli fused to maltose binding protein (MBP). The purified MBP-FHc and FHc isolated after removal of MBP were evaluated in mice for their ability to protect against toxin challenge. Balb/c mice developed a protective immune response following administration of either protein via the intraperitoneal or intramuscular routes. A comparison of antibody titres and protection following single and multiple vaccinations and the effects of dosage are shown. The long term protection afforded by the vaccines was also investigated. Ten months following vaccination mice were still protected when challenged with 10(4) MLD(50) doses of botulinum toxin F.

ATP-Binding Cassette Transporters↗
PubMed1999

Analysis of murine Snrpn and human SNRPN gene imprinting in transgenic mice.

The SNRPN gene is known to be expressed exclusively from the paternal allele and to map to the critical region for the neurobehavioral disorder, Prader-Willi syndrome (PWS). As a means to investigate the mechanism of imprinting for the SNRPN gene, we have sought to recapitulate the imprinted expression of the endogenous gene. Using an 85-kb murine Snrpn clone, containing 33 kb of 5' and 30 kb of 3' flanking DNA, we obtained two intact transgenic lines. One line, containing two copies of the Snrpn transgene, recapitulated the imprinted expression pattern of the endogenous locus, whereas the other transgenic line, containing a single copy, was expressed upon both maternal and paternal inheritance. This suggests that a 6.6-kb region of maternal-specific DNA methylation that we have identified may be sufficient to confer imprinted expression, but not in a copy-number independent manner. Finally, we produced five lines of transgenic mice using a 76-kb human SNRPN clone containing 45 kb and 7 kb of 5' and 3' flanking DNA, respectively. We found all the lines were expressed upon both maternal and paternal inheritance, regardless of copy number, suggesting that the imprinting machinery in mouse and human may have diverged.

Animals↗
PubMed1999

Thoughts of harming infants in depressed and nondepressed mothers.

BACKGROUND: Thoughts of harming the infant and other disturbing cognitions are frequently described in anecdotal reports on postpartum depression. These cognitions have not been examined empirically. METHODS: 100 clinically depressed mothers with a child under 3 years were evaluated and compared to a control group of 46 nondepressed mothers. RESULTS: 41% of depressed mothers compared to 7% of control mothers admitted to thoughts of harming their infant. Fear of being alone with the infant and inability to care for the infant were assessed only in depressed mothers and occurred less frequently. More than half of depressed mothers had problems in one of these three areas. CONCLUSIONS: Thoughts of harming the infant are common in depressed mothers. Demographic variables, psychosocial stressors and psychiatric variables do not help predict which mothers are likely to experience thoughts of harm or fear of being alone with the infant. These cognitive and affective disturbances may be one pathway by which maternal depression affects infants. LIMITATIONS: The control group was not given the full diagnostic interview. Consequently, the groups were not selected by identical procedures. Also fear of being alone with the infant and difficulty caring for the infant were not assessed in the control group.

Child Abuse↗
PubMed1994

Mechanism of inhibition of protein kinase C by 14-3-3 isoforms. 14-3-3 isoforms do not have phospholipase A2 activity.

The ability of individual members of the 14-3-3 protein family to inhibit protein kinase C (PKC) has been studied by using a synthetic peptide based on the specific 80 kDa substrate for PKC (MARCKS protein) in two different assay systems. Recombinant 14-3-3 and isoforms renatured by a novel method after separation by reverse-phase h.p.l.c. were studied. The detailed effects of diacylglycerol and the phorbol ester phorbol 12-myristate 13-acetate on the inhibition were also investigated. This suggests that one of the sites of interaction of 14-3-3 may be the cysteine-rich (C1) domain in PKC. Since a region in secreted phospholipase A2 (PLA2) shares similarity with this domain, the ability of 14-3-3 to interact with mammalian PLA2 was studied. Cytosolic PLA2 has some similarity to the C2 region of PKC, and the effect of 14-3-3 on this class of PLA2 was also analysed. In contrast with a previous report, no PLA2 activity was found in brain 14-3-3, nor in any of the recombinant proteins tested. These include zeta 14-3-3 isoform, on which the original observation was made.

14-3-3 Proteins↗
PubMed1991

Comparison of the role of protein kinase C in platelet functional responses induced by three different mechanisms, PAF, ionomycin and arachidonic acid.

The role of protein kinase C (PKC) in modulating platelet activation has been examined in platelets pre-incubated with either the PKC activator 12-O-tetradecanoylphorbol 13-acetate (TPA) or the non-specific protein kinase inhibitor, staurosporine. In order to determine where in the signal transduction pathway PKC is exerting its effect platelets were activated either with a receptor-operated stimulus platelet activating factor (PAF) or by direct elevation of [Ca2+]i (ionomycin) or with arachidonic acid which is converted into thromboxane B2 (TxB2). In PAF-stimulated platelets activation of PKC inhibited both [Ca2+]i elevation and TxB2 generation but had no effect on 5-hydroxytryptamine (5-HT) release whilst staurosporine increased the duration of [Ca2+]i elevation and potentiated TxB2 generation but inhibited 5-HT release. In ionomycin-stimulated platelets modulation of PKC had no effect on [Ca2+]i elevation but in contrast to PAF-stimulated platelets PKC activation caused potentiation of TxB2 generation and 5-HT release whilst inhibition of PKC caused inhibition of TxB2 generation and 5-HT release. Modulation of PKC did not affect arachidonic acid-induced TxB2 generation. These findings suggest that in receptor activated platelets endogenously activated PKC is exerting a negative feedback role, however, when [Ca2+]i elevation is not modified by PKC activation or inhibition (such as in ionomycin stimulated platelets) the relationship between the state of PKC activation and subsequent platelet functional responses corresponds more closely. The findings from this study suggest a different relationship between PKC and TxB2 generation than between PKC and dense granule release in PAF-stimulated platelets.

Alkaloids↗
PubMed1991

The relationship between cytosolic Ca2+, sn-1,2-diacylglycerol and inositol 1,4,5-trisphosphate elevation in platelet-activating-factor-stimulated rabbit platelets. Influence of protein kinase C on production of signal molecules.

The temporal and dose-response relationships of platelet-activating-factor (PAF)-induced changes in the concentrations of cytosolic Ca2+ ([Ca2+]i), Ins(1,4,5)P3 and 1,2-diacylglycerol (DAG) were examined. In addition, phosphorylation of protein kinase C (PKC) substrate (40-47 kDa protein) was determined. In high-dose PAF-activated platelets, all three signal molecules increased rapidly and transiently, with the peak Ins(1,4,5)P3 concentration preceding maximal elevation of [Ca2+]i by 5 s. In low-dose PAF-activated platelets there were large increases in [Ca2+]i and dense-granule release, without any increase in Ins(1,4,5)P3 and DAG or 40-47 kDa protein phosphorylation. Staurosporine, a non-specific PKC inhibitor, produced enhanced elevations in the concentrations of Ins(1,4,5)P3, DAG and thromboxane B2, and the duration of the Ca2+ signal in platelets stimulated with a high dose, but not a low dose, of PAF. These results suggest there are both phospholipase C-dependent and -independent changes in Ca2+ homoeostasis. Endogenously activated PKC regulates the formation of signal molecules.

Alkaloids↗
PubMed1990

Degradation of thyrotropin-releasing hormone and luteinising hormone-releasing hormone by enzymes of brain tissue.

In this article, the enzymes of brain and associated tissues that can degrade thyrotropin-releasing hormone (TRH) and luteinising hormone-releasing hormone (LH-RH) are reviewed. As both TRH and LH-RH are considered to act as neurotransmitters or neuromodulators in the CNS, attention is paid to the subcellular location of the enzymes described and how their topographies and substrate specificities fit them to playing roles as inactivating agents for TRH and LH-RH or as regulators of intracellular concentrations of TRH and LH-RH. Consideration is also given to enzymes involved in biotransformation of TRH to secondary metabolites that exhibit biological activity and to enzymes involved in the metabolism of secondary metabolites.

Amino Acid Sequence↗
PubMed1988

Comparison of radially sensitive and circumferentially sensitive microtransducer esophageal manometry probes in normal subjects.

Circumferentially sensitive microtransducer probes are commercially available for use in esophageal manometry, and may offer an advantage over radially sensitive microtransducer probes in sphincters with radial asymmetry. In order to compare performance of the two probes, we performed esophageal manometry in 30 healthy adult volunteers with both probes. In only three of 52 manometric parameters measured were differences between mean values for the two probes statistically significant. Intrasubject variability was significantly (p = less than 0.005) less with the circumferentially sensitive probe (coefficient of variation 37% vs. 53%).

Adult↗
PubMed1984

Detection of surgical lesions of the small bowel by enteroclysis.

Enteroclysis is an examination in which barium is infused directly into the small intestine, and compression radiographs are taken on each segment. This method eliminates many of the inherent limitations of the conventional small bowel follow-through examination. This report concerns 45 patients with 48 small bowel lesions. They were missed on the conventional examination but detected within 3 months by subsequent enteroclysis and confirmed surgically. There were 15 patients with Meckel's diverticula, 7 with obstructive adhesive bands, 5 with Crohn's disease, 5 with blind pouch syndrome (1 with a leiomyoma inside the blind pouch), 2 with other leiomyomas, 3 with metastatic carcinoma, two with primary carcinoma 3 with radiation stricture, two with sinus tract lesions and fistulas, and 1 with another lesion. Improved intubation techniques and better barium mixtures make enteroclysis possible in most hospitals. As surgeons appreciate the value of enteroclysis, they can request this examination for appropriate patients to sooner find many surgical lesions of the small bowel which frequently go undiagnosed.

Adult↗
PubMed1982

Screening examination of the larynx and pharynx during upper gastrointestinal panendoscopy.

With the flexible fiberoptic esophagogastroduodenoscopes now in use, the larynx and posterior pharynx can be easily viewed during routine upper gastrointestinal endoscopy. Screening laryngeal-pharyngeal examinations were carried out during 1120 upper gastrointestinal endoscopies. Mean additional examination time was 30 sec. Thirty-nine laryngeal lesions were detected, mostly variants of chronic laryngitis. Two patients had leukoplakia, one of whom on subsequent biopsy revealed squamous cell cancer. The brief additional endoscopic time may result in the detection of early curable neoplasms. Thus a screening laryngeal-pharyngeal examination should be part of each upper gastrointestinal endoscopic examination.

Carcinoma, Squamous Cell↗