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J Morehead

Publications and source records attributed to J Morehead.

9 recordsLinked to original sources
PubMed2002

Opsonization modulates Rac-1 activation during cell entry by Leishmania amazonensis.

Lesions caused by Leishmania amazonensis normally heal, but relapses occur due to parasite persistence in host tissues. It has been proposed that infection of fibroblasts plays an important role in this process by providing the parasites with a safe haven in which to replicate. However, most previous studies have focused on the entry of Leishmania into macrophages, a process mediated by serum opsonins. To gain insight into a possible role of nonopsonic entry in the intracellular persistence of amastigotes, we examined the invasion of Chinese hamster ovary (CHO) cells. Amastigotes entered CHO cells by a cytochalasin D, genistein, wortmannin, and 2,3-butanedione monoxime-sensitive pathway and replicated within phagolysosomes. However, unlike most phagocytic processes described to date, amastigote internalization in CHO cells involved activation of the GTPases Rho and Cdc42 but not Rac-1. When uptake was mediated by fibronectin or when amastigotes were opsonized with immunoglobulin G and internalized by Fc receptor-expressing CHO cells, Rac-1 activation was restored and found to be required for parasite internalization. Given the essential role of Rac in assembly of the respiratory burst oxidase, invasion through this nonopsonic, Rac-1-independent pathway may play a central role in the intracellular survival of Leishmania in immune hosts.

Animals↗
PubMed2000

Synaptotagmin VII regulates Ca(2+)-dependent exocytosis of lysosomes in fibroblasts.

Synaptotagmins (Syts) are transmembrane proteins with two Ca(2+)-binding C(2) domains in their cytosolic region. Syt I, the most widely studied isoform, has been proposed to function as a Ca(2+) sensor in synaptic vesicle exocytosis. Several of the twelve known Syts are expressed primarily in brain, while a few are ubiquitous (Sudhof, T.C., and J. Rizo. 1996. Neuron. 17: 379-388; Butz, S., R. Fernandez-Chacon, F. Schmitz, R. Jahn, and T.C. Sudhof. 1999. J. Biol. Chem. 274:18290-18296). The ubiquitously expressed Syt VII binds syntaxin at free Ca(2+) concentrations ([Ca(2+)]) below 10 microM, whereas other isoforms require 200-500 microM [Ca(2+)] or show no Ca(2+)-dependent syntaxin binding (Li, C., B. Ullrich, Z. Zhang, R.G.W. Anderson, N. Brose, and T.C. Sudhof. 1995. Nature. 375:594-599). We investigated the involvement of Syt VII in the exocytosis of lysosomes, which is triggered in several cell types at 1-5 microM [Ca(2+)] (Rodríguez, A., P. Webster, J. Ortego, and N.W. Andrews. 1997. J. Cell Biol. 137:93-104). Here, we show that Syt VII is localized on dense lysosomes in normal rat kidney (NRK) fibroblasts, and that GFP-tagged Syt VII is targeted to lysosomes after transfection. Recombinant fragments containing the C(2)A domain of Syt VII inhibit Ca(2+)-triggered secretion of beta-hexosaminidase and surface translocation of Lgp120, whereas the C(2)A domain of the neuronal- specific isoform, Syt I, has no effect. Antibodies against the Syt VII C(2)A domain are also inhibitory in both assays, indicating that Syt VII plays a key role in the regulation of Ca(2+)-dependent lysosome exocytosis.

Animals↗
PubMed1999

Oligopeptidase B from Trypanosoma brucei, a new member of an emerging subgroup of serine oligopeptidases.

Trypanosoma brucei contains a soluble serine oligopeptidase (OP-Tb) that is released into the host bloodstream during infection, where it has been postulated to participate in the pathogenesis of African trypanosomiasis. Here, we report the identification of a single copy gene encoding the T. brucei oligopeptidase and a homologue from the related trypanosomatid pathogen Leishmania major. The enzymes encoded by these genes belong to an emerging subgroup of the prolyl oligopeptidase family of serine hydrolases, referred to as oligopeptidase B. The trypanosomatid oligopeptidases share 70% amino acid sequence identity with oligopeptidase B from the intracellular pathogen Trypanosoma cruzi, which has a demonstrated role in mammalian host cell signaling and invasion. OP-Tb exhibited no activity toward the prolyl oligopeptidase substrate H-Gly-Pro-7-amido-4-methylcoumarin. Instead, it had activity toward substrates of trypsin-like enzymes, particularly those that have basic amino acids in both P(1) and P(2) (e.g. benzyloxycarbonyl-Arg-Arg-7-amido-4-methylcoumarin k(cat)/K(m) = 529 s(-1) microM(-1)). The activity of OP-Tb was enhanced by reducing agents and by polyamines, suggesting that these agents may act as in vivo regulators of OP-Tb activity. This study provides the basis of the characterization of a novel subgroup of serine oligopeptidases from kinetoplastid protozoa with potential roles in pathogenesis.

Amino Acid Sequence↗
PubMed1993

Digital nerves of the foot: anatomic variations and implications regarding the pathogenesis of interdigital neuroma.

Seventy-one cadaveric feet were dissected, with attention to communicating branches of the digital nerves, the diameters of the digital nerves, the distance between the metatarsal heads, and the presence or absence of interdigital neuromas. A communicating branch was absent in 52 feet (73.2%) and present in 19 specimens (26.8%). The communication was from the fourth to the third web space common digital nerve (i.e., from the lateral to the medial plantar nerve) in 11 specimens. A reverse communication, from the third to the fourth web space common digital nerve (i.e., from the medial to the lateral plantar nerve), was present in eight specimens. Neuromas were identified in the second web space in 26 specimens and in the third web space in 32 feet. The common digital nerve to the third web space was not thicker in feet with a contribution from the fourth to the third web space nerve. Additionally, the incidence of third web space neuroma in feet with this type of communication was not significantly greater than in those feet without an internervous communication. However, the intermetatarsal head distances and the ratios of the intermetatarsal head distance to the digital nerve diameter in web spaces 2 and 3 were significantly smaller in comparison to spaces 1 and 4 (P < .05). The morphometric data lend support to theories that explain the propensity for neuroma formation in both the second and third web spaces on a mechanical basis.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1990

Maxillary sinus hypoplasia: classification and description of associated uncinate process hypoplasia.

Maxillary sinus hypoplasia is an anomaly of the paranasal sinuses occasionally encountered by otolaryngologists. Although this entity has been previously reported, an association between maxillary sinus hypoplasia and anomalies of other paranasal sinus structures, such as the uncinate process, has not yet been described. Additionally, the literature lacks a system by which the various types of maxillary sinus hypoplasia can be classified using computerized tomographic (CT) imaging. Two hundred and two consecutive coronal sinus computerized tomographic scans from patients undergoing evaluation at our institution were analyzed to determine the prevalence of MSH and associated paranasal sinus anomalies. The overall prevalence of maxillary sinus hypoplasia was 10.4%. Three distinct patterns of hypoplasia were evident. Type I, characterized by a normal uncinate process, a well-defined infundibular passage, and mild sinus hypoplasia, occurred in 14 patients (6.9%). Type II, characterized by absence or hypoplasia of the uncinate process, an ill-defined infundibular passage, and soft-tissue density opacification of a significantly hypoplastic sinus occurred in 6 patients (3.0%). Type III, characterized by absence of the uncinate process and a profoundly hypoplastic, cleft-like sinus, occurred in 1 patient (0.5%). Recognition of associated anomalies of the uncinate process in patients with maxillary sinus hypoplasia undergoing sinus surgery is of utmost clinical significance because the uncinate process serves as a key landmark during functional endoscopic sinus surgery. Failure to recognize hypoplasia or absence of the uncinate process could lead to inadvertent intraoperative damage to the adjacent medial orbital wall.

Abnormalities, Multiple↗
PubMed1976

Menstrual blood-loss with intrauterine devices.

The effect of three intrauterine contraceptive devices (I.U.D.)-Lippes D, Dalkon Shield, and Copper 7-on menstrual blood-loss has been studied serially by objective methods in 279 women. All the women had a minimum of two cycles following delivery, abortion, cessation of lactation, or previous pill or I.U.D. use. All pads and tampons used for two further menstrual cycles before and for 12 cycles after I.U.D. insertion were collected, and the blood-loss was measured by extracting the haemoglobin by conversion to alkaline haematin. Mean menstrual blood-loss increased with all three devices. The amount of loss, the percentage of women losing more than 80 ml, the decline in haemoglobin concentration, and the incidence of anaemia during the 12 cycles following insertion were all greater among users of the Lippes Loop than of the Copper 7 with generally intermediate values for Dalkon Shield users. The mean increases in blood-loss were: for parous women fitted with the Lippes Loop, 48 ml, with the Dalkon Shield, 34 ml, and with the Copper 7, 18 ml; for nulliparae fitted with the small size of Dalkon Shield, 27 ml, and, with the Copper 7, 19 ml.

Blood Specimen Collection↗