Biomedical subjects

L D Martin

Publications and source records attributed to L D Martin.

At least 19 recordsLinked to original sources

PubMed2005

Extinction may not be forever.

Here we review the phenomenon of ecomorph evolution and the hypothesis of iterative climatic cycles. Although a widely known phenomenon, convergent evolution has been underappreciated in both its scope and commonality. The power of natural selection to override genealogy to create similar morphologies (even among distantly related organisms) supports classical Darwinian evolution. That this occurs repeatedly in stratigraphically closely spaced intervals is one of the most striking features of Earth history. Periodic extinctions followed by re-evolution of adaptive types (ecomorphs) are not isolated occurrences but are embedded within complex ecological systems that evolve, become extinct, and repeat themselves in temporal synchrony. These complexes of radiation and extinction bundle the biostratigraphic record and provide the basis for a global stratigraphy. At this scale, climatic change is the only mechanism adequate to explain the observed record of repeating faunas and floras. Understanding of the underlying causes may lead to predictive theories of global biostratigraphy, evolutionary processes, and climatic change.

Animals↗

PubMed2003

Epidemiologic study of tumors in dinosaurs.

Occasional reports in isolated fragments of dinosaur bones have suggested that tumors might represent a population phenomenon. Previous study of humans has demonstrated that vertebral radiology is a powerful diagnostic tool for population screening. The epidemiology of tumors in dinosaurs was here investigated by fluoroscopically screening dinosaur vertebrae for evidence of tumors. Computerized tomography (CT) and cross-sections were obtained where appropriate. Among more than 10,000 specimens x-rayed, tumors were only found in Cretaceous hadrosaurs (duck-billed dinosaurs). These included hemangiomas and metastatic cancer (previously identified in dinosaurs), desmoplastic fibroma, and osteoblastoma. The epidemiology of tumors in dinosaurs seems to reflect a familial pattern. A genetic propensity or environmental mutagens are suspected.

Animals↗

PubMed2003

Extinction and re-evolution of similar adaptive types (ecomorphs) in Cenozoic North American ungulates and carnivores reflect van der Hammen's cycles.

Numerous patterns in periodicity (e.g., climate, extinction, and sedimentary cycles) and evolutionary change (e.g., chronofaunas and coordinated stasis) have been described based on aspects of the geologic record. Recently, convergent occurrences of faunal types or "repeating faunas" have received attention, but a highly specific, iterative pattern was first reported over 40 years ago. In the late 1950s, van der Hammen described climatic/floral cycles on the order of six million years based on a succession of A, B, and C pollen community types in South America. These A-B-C cycles are also seen in the replacement pattern of particular carnivore and ungulate adaptive types in Cenozoic North America as reported by Martin in the 1980s. For example, in the last 36 million years, there were four iterations of a sabertooth cat ecomorph independently evolving, dominating the niche through an A-B-C cycle, and then going extinct. Here we show further support for the existence of these cycles in the dominance turnover in hippo and dog ecomorphs in the North American Cenozoic. Shared patterns of extinction and re-evolution of adaptive types among plants and mammals across two continents suggest a global mechanism, which appears to be climatic change. Iterative climatic cycles of various scales may form a predictive framework for understanding fundamental patterns in the geologic record, such as radiations, extinction, rates of change, convergence, and sedimentary cycles.

Acclimatization↗

PubMed2003

Frequency of pathology in a large natural sample from Natural Trap Cave with special remarks on erosive disease in the Pleistocene.

Population data are presented for erosive arthritis, osteoarthritis, diffuse idiopathic skeletal hyperostosis (DISH), joint eburnation and dental injury in a fauna from Natural Trap Cave, Wyoming, represented by over thirty thousand bones from twenty-four different species. Erosive arthritis is limited to the bovids, Bison, Ovis and Bootherium. Erosive arthritis is also present in bison from the late Pleistocene Twelve Mile Creek site in Kansas and from an early Holocene site in Wisconsin. The restriction of the known Pleistocene occurrences to bovids indicate the presence of a pathogen that predisposes bovids to erosive arthritis. The pathogen was identified as Mvcobacterium tuberculosis. Osteoarthritis and DISH are rare in the Natural Trap Cave, although Bison shows a relatively high occurrence of the former. Tooth breakage due to errors in bone manipulation was a problem for carnivores and one lion, Pantera atrox, was apparently reduced by joint disease to a scavenging lifestyle.

Animals↗

PubMed2002

A new fossil mustelid from the Miocene of South Dakota, USA.

A skull from the Barstovian of South Dakota has typical leptarctine characteristics, including robust zygomatic arches, double sagittal crests, grooves on the lingual side of the lower canines, and bony projections from the tympanic bullae. The robust mandibles and expanded masseteric fossa of this specimen indicate that it had large jaw muscles. Dental morphology and other characters lead us to agree with earlier suggestions that Hypsoparia is a valid genus. The morphology of Hypsoparia suggests that leptarctines were more herbivorous than most other Carnivora. Mustelids vary greatly in size and include 67 extant species in 25 genera. These species occupy many habitats, including fresh and salt water, and all land areas of the world except the West Indies, Madagascar, Sulawesi, Antarctica, and most oceanic islands (Nowak 1999). Qiu and Schmidt-Kittler (1982) considered Leptarctinae to be a subfamily of mustelids including Craterogale (North America, Middle Miocene), Trocharion (Europe, Middle Miocene), Hypsoparia (North America, Upper Miocene), and Leptarctus (North America and Asia, Lower to Upper Miocene). Leptarctus ranges from basal Hemingfordian strata to the Early Hemphillian (Lim 1999). The characters diagnosing Leptarctus as a mustelid include absence of M2, absence of a notch between the paracone and the metacone of the upper carnassial, and a reduced dentition with loss of P1 and p1. Among mustelids, Leptarctus also has many unique characters, including prominent double sagittal crests, a well-developed hypocone on P4, grooved lower canines, heavy zygomatic arches, and bony projections on the tympanic bullae (Lim 1999). Dorr (1954) erected a new genus and species of leptarctine mustelid from the Late Miocene of Montana, USA: Hypsoparia bozemanensis. Qiu and Schmidt-Kittler (1982) confirmed it as a taxon separate from Leptarctus. However, McKenna and Bell (1997) and Baskin (1998) synonymized H. bozemanensis with Leptarctus primus. The new specimen from the Miocene of South Dakota, USA, provides evidence that Hypsoparia is a separate genus from Leptarctus. We can describe this animal as follows: Systematic paleontology: class, Mammalia; order, Carnivora; family, Mustelidae (Fischer von Waldheim 1817); subfamily, Leptarctinae (Gazin 1936); genus Hypsoparia (Dorr 1954). Emended diagnosis: the muzzle short, deep, and wide compared with that of Leptarctus; small, round infraorbital foramen; relatively greater height of zygomatic arch; upper canine with anterior wear; P2 and P3 unicuspid with complete cingula; P4 and M1 longer than wide; labial side longer than lingual side on P4; anterior margin of M1 curving inward; mandibles larger and more robust than in L. primus; mandible deep with two mental foramina located below p2 and p3; masseteric fossa enlarged; m2 longer than wide; m1 with a broadly basined talonid; p3 and p4 with prominent cingula.

Animals↗

PubMed2001

MARCKS protein is a key molecule regulating mucin secretion by human airway epithelial cells in vitro.

Hypersecretion of airway mucin characterizes numerous respiratory diseases. Although diverse pathological stimuli can provoke exocytotic release of mucin from secretory cells of the airway epithelium, mechanisms involved remain obscure. This report describes a new paradigm for the intracellular signaling mechanism regulating airway mucin secretion. Direct evidence is provided that the myristoylated alanine-rich C kinase substrate (MARCKS) is a central regulatory molecule linking secretagogue stimulation at the cell surface to mucin granule release by differentiated normal human bronchial epithelial cells in vitro. Down-regulation of MARCKS expression or disruption of MARCKS function in these cells inhibits the secretory response to subsequent stimulation. The intracellular mechanism controlling this secretory process involves cooperative action of two separate protein kinases, protein kinase C and cGMP-dependent protein kinase. Upon stimulation, activated protein kinase C phosphorylates MARCKS, causing translocation of MARCKS from the plasma membrane to the cytoplasm, where it is then dephosphorylated by a protein phosphatase 2A that is activated by cGMP-dependent protein kinase, and associates with both actin and myosin. Dephosphorylated cytoplasmic MARCKS would also be free to interact with mucin granule membranes and thus could link granules to the contractile cytoskeleton, mediating their movement to the cell periphery and subsequent exocytosis. These findings suggest several novel intracellular targets for pharmacological intervention in disorders involving aberrant secretion of respiratory mucin and may relate to other lesions involving exocytosis of membrane-bound granules in various cells and tissues.

Actins↗

PubMed2001

Mycobacterium tuberculosis complex DNA from an extinct bison dated 17,000 years before the present.

In order to assess the presence of tuberculosis in Pleistocene bison and the origin of tuberculosis in North America, 2 separate DNA extractions were performed by 2 separate laboratories on samples from the metacarpal of an extinct long-horned bison that was radiocarbon dated at 17,870+/-230 years before present and that had pathological changes suggestive of tuberculosis. Polymerase chain reaction amplification isolated fragments of tuberculosis DNA, which were sequenced, and on which spoligotyping was also performed to help determine its relationship to the various members of the Mycobacterium tuberculosis complex. Extensive precautions against contamination with modern M. tuberculosis complex DNA were employed, including analysis of paleontologic and modern specimens in 2 geographically separate laboratories.

Animals↗

PubMed2001

The first discovery of a brachiosaurid from the Asian continent.

Described here is a sauropod tooth from the Early Cretaceous of South Korea, similar to Brachiosaurus. The crown of the tooth is beveled off lingually so that when worn it presents a chisel-like edge. This find confirms the presence of a brachiosaurid in East Asia during the Early Cretaceous.

Animals↗

PubMed2001

Enhanced expression of mucin genes in a guinea pig model of allergic asthma.

The ovalbumin (OVA)-sensitized guinea pig is often used as an animal model of asthma and airway hyperreactivity. A characteristic lesion of asthma is excessive production of mucin in the airways. Mechanistic studies of this lesion in guinea pigs have been limited due to lack of mucin gene probes for this species. The aim of the present study was to clone the cDNAs encoding two major airway mucins (Muc2 and Muc5ac) from the guinea pig, and investigate mucin gene expression in lungs of sensitized animals in response to antigen challenge. We isolated and sequenced two cDNA fragments coding for the sequences located within the carboxyl-terminal cysteine-rich region of guinea pig Muc2 and Muc5ac mucins. Comparison of cloned cDNAs with those from other species revealed high degrees of sequence identity and conservation of all cysteine residues in deduced primary sequences. Based on the resultant sequence information, we also designed oligonucleotide primers for specific detection of guinea-pig Muc2 and Muc5ac steady-state mRNA levels via reverse transcriptase/ polymerase chain reaction (RT-PCR). Levels of both Muc2 and Muc5ac mRNA in lungs of OVA-sensitized guinea pigs increased significantly by 30 min after an acute exposure to 0.3% OVA. In addition, levels of eotaxin mRNA also increased in these tissues, but the increases were not significant until 2 h after challenge. Correspondingly, the number of eosinophils in bronchoalveolar lavage fluid did not increase until 4 h postchallenge. Results of these studies suggest that the OVA-sensitized guinea pig responds to allergic challenge with enhanced expression of genes (e.g., eotaxin, Muc2, and Muc5ac) that likely play a role in increased airway inflammation and mucin overproduction, and enhanced mucin gene expression appears to occur before eosinophil infiltration.

Amino Acid Sequence↗

PubMed2001

Interleukin-13 induces proliferation of human airway epithelial cells in vitro via a mechanism mediated by transforming growth factor-alpha.

Remodeling of the airways, as occurs in asthmatic patients, is associated with the continual presence of inflammatory mediators and Th2 cytokines, especially interleukin (IL)-13, during cycles of epithelial injury and repair. In this study, we examined the effect of IL-13 on well-differentiated normal human bronchial epithelial (NHBE) cells maintained in air-liquid interface culture. IL-13 induced proliferation of NHBE cells after 24 h exposure, as reflected by [(3)H]thymidine uptake and cell counts. The effects of IL-13 were mediated through the epidermal growth factor receptor (EGFR), as proliferation was attenuated by AG1478, an EGFR tyrosine kinase inhibitor. Proliferation appeared to be mediated by transforming growth factor (TGF)-alpha, a potent ligand for EGFR, which was released rapidly from NHBE cells in response to IL-13. Neutralizing antibody to TGF-alpha, but not antibodies against other potentially important growth factors (EGF, heparin binding epidermal growth factor-like growth factor [HB-EGF], platelet-derived growth factor [PDGF]), inhibited the mitogenic response to IL-13. This study provides the first experimental evidence that IL-13 can initiate a proliferative response of human airway epithelium in the absence of inflammatory cells or other cell types. The results are consistent with a mechanism whereby IL-13 induces release of TGF-alpha from the epithelial cells, which in turn binds via an autocrine/paracrine-type action to the EGFR, initiating proliferation. IL-13-induced airway remodeling in vivo may involve this epithelium-driven response.

Bronchi↗

PubMed2000

Nonavian feathers in a late Triassic archosaur.

Longisquama insignis was an unusual archosaur from the Late Triassic of central Asia. Along its dorsal axis Longisquama bore a series of paired integumentary appendages that resembled avian feathers in many details, especially in the anatomy of the basal region. The latter is sufficiently similar to the calamus of modern feathers that each probably represents the culmination of virtually identical morphogenetic processes. The exact relationship of Longisquama to birds is uncertain. Nevertheless, we interpret Longisquama's elongate integumentary appendages as nonavian feathers and suggest that they are probably homologous with avian feathers. If so, they antedate the feathers of Archaeopteryx, the first known bird from the Late Jurassic.

Animals↗

PubMed2000

Residual oil fly ash induces cytotoxicity and mucin secretion by guinea pig tracheal epithelial cells via an oxidant-mediated mechanism.

Inhalation of ambient air particulate matter (PM) is associated with pulmonary injury and inflammation. Using primary cultures of guinea pig tracheal epithelial (GPTE) cells as an in vitro model of airway epithelium, we examined effects of exposure to suspensions of six different emission and ambient air PM samples: residual oil fly ash (ROFA) from an electrical power plant; fly ash from a domestic oil burning furnace (DOFA); ambient air dust from St. Louis (STL), Ottawa (OT), and Washington, DC (WDC); and volcanic ash from the eruption of Mount Saint Helens (MSH) in 1980. Effects of these particulates on cell viability (assessed via LDH assay), secretion of mucin (measured by a monoclonal antibody-based ELISA), and steady-state mRNA levels of the mucin gene MUC2 were determined. ROFA was the most toxic of the dusts tested, as it significantly increased LDH release following a 24-h incubation with 50 microg/cm(2) ROFA. ROFA also enhanced MUC2 mRNA after 4-h exposure, and mucin secretion after 8 h. ROFA-induced mucin secretion and cytotoxicity were attenuated by the oxidant scavenger, dimethylthiourea (DMTU). ROFA exposure also depleted cells of glutathione (GSH). Relatedly, depletion of intracellular GSH by treatment of the cells with buthionine sulfoxamine (BSO) also provoked mucin secretion, as well as enhancing the secretory effect of ROFA when the two agents were added together. L-NMA, the nitric oxide synthase (NOS) inhibitor, did not affect ROFA-induced mucin secretion. Of the soluble transition metals in ROFA (nickel, iron, vanadium), only vanadium individually, or combinations of the metals containing vanadium, provoked secretion. The results suggest ROFA enhances mucin secretion and generates toxicity in vitro to airway epithelium via a mechanism(s) involving generation of oxidant stress, perhaps related to depletion of cellular antioxidant capacity. Deleterious effects of inhalation of ROFA in the respiratory tract in vivo may relate to these cellular responses. Vanadium, a component of ROFA, may be important in generating these reactions.

Animals↗

PubMed2000

Three ways to be a saber-toothed cat.

Saber-toothed carnivores, until now, have been divided into two groups: scimitar-toothed cats with shorter, coarsely serrated canines coupled with long legs for fast running, and dirk-toothed cats with more elongate, finely serrated canines coupled to short legs built for power rather than speed. In the Pleistocene of North America, as in Europe, the scimitar-cat was Homotherium; the North American dirk-tooth was Smilodon. We now describe a new sabercat from the Early Pleistocene of Florida, combining the scimitar-tooth canine with the short, massive limbs of a dirk-tooth predator. This presents a third way to construct a saber-toothed carnivore.

Animals↗

PubMed2000

The oldest known tracks of web-footed birds from the lower Cretaceous of South Korea.

We describe the oldest tracks of web-footed birds from the Early Cretaceous in South Korea. The tracks are characterized by a wide divarication angle and a long reversed hallux. The web is semipalmate and restricted to the proximal portion of the three forward digits. The tracks from the Early Cretaceous in South Korea are smaller than those of the Late Cretaceous, therefore confirming the trend of size increasing in the early evolution of birds as shown by skeletal fossils. The discovery of web-footed tracks with abundant non-web-footed tracks indicates that there was a considerable diversification of shore birds as early as the Early Cretaceous.

Animals↗

PubMed2000

Outcome of children who require mechanical ventilatory support after bone marrow transplantation.

OBJECTIVE: To identify clinically measurable factors that could predict outcome for pediatric patients undergoing mechanical ventilatory support after bone marrow transplant. DESIGN: Cohort study. SETTING: A referral center for bone marrow transplant patients in Seattle, Washington. PATIENTS: Children <17 yrs old who received a bone marrow transplant and subsequently required mechanical ventilatory support for > or =24 hrs between 1983 and 1996. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data were abstracted from the charts of 121 pediatric patients who received a bone marrow transplant and subsequently required mechanical ventilatory support. A total of 19 patients (16%) survived to be extubated and survived for > or =30 days postextubation. Major risk factors for death included respiratory failure as the reason for endotracheal intubation (4% survival), the presence of pulmonary infection (6% survival), and impairment of more than one organ system (2% survival if more than one organ system was dysfunctional on day 7 postintubation). CONCLUSIONS: Although the prognosis generally is poor among pediatric bone marrow transplant recipients who subsequently require mechanical ventilatory support, there appear to be some groups within this population in whom the likelihood of survival is close to 0. Because the chance of survival was so small for children with dysfunction of more than one organ system on day 7 after intubation, a recommendation to limit medical support for these children could be considered pending the results of other studies.

Adolescent↗

PubMed2000

Targeted disruption of the endothelin-B-receptor gene attenuates inflammatory nociception and cutaneous inflammation in mice.

Endothelin-1 (ET-1) has been suggested to have a potential function as an inflammatory mediator. The study reported here assessed the putative inflammatory/nociceptive actions of the ET isopeptides using endothelin-B (ET(B))-receptor knockout (KO) mice and ET(A)- (SB 234551) and ET(B)- (A192621) selective antagonists. Phenylbenzoquinone (PBQ)-induced algesia was evident in the wild-type (WT) ET(B) (+/+) mice, attenuated by 80% in the heterozygous ET(B) (+/-) mice, and absent in the ET(B) (-/-) homozygotes. This was reproduced pharmacologically in WT ET(B) (+/+) mice where the algesic effect of PBQ was inhibited 74% by A192621, but unaffected by SB 234551 (both at 25 mg/kg p.o.). Similar observations were made in a model of cutaneous inflammation: ET(B) (+/+) mice had a marked inflammatory response to topical arachidonic acid, ET(B) (+/-) and ET(B) (-/-) mice had significantly reduced edema responses (37% and 65% inhibition). Neutrophil infiltration was reduced in the ET(B) (+/-) and ET(B) (-/-) mice (51% and 65% reduction, respectively). Topical administration of A192621 (500 microg/ear) inhibited arachidonic acid-induced swelling (39%) in WT ET(B) (+/+) mice. Collectively, these results support a role for the ET(B)-receptor in the mediation of inflammatory pain and cutaneous inflammatory responses. As such, the development of ET(B)-receptor-selective antagonists may be of therapeutic utility in the treatment of inflammatory disorders.

Animals↗

PubMed2000

Effects of TNF-alpha on expression of ICAM-1 in human airway epithelial cells in vitro. Signaling pathways controlling surface and gene expression.

Signaling pathways associated with tumor necrosis factor (TNF)-alpha-induced intercellular adhesion molecule 1 (ICAM-1) surface and gene expression were investigated in well differentiated normal human bronchial epithelial (NHBE) cells in air-liquid interface primary culture. Cells were exposed to human recombinant TNF-alpha (hrTNF-alpha; 0.015 to 150 ng/ml [specific activity, 2.86 x 10(7) U/mg]). TNF-alpha enhanced ICAM-1 surface expression (measured by flow cytometry) and steady-state messenger RNA (mRNA) levels (assessed by Northern hybridization) in concentration- and time-dependent manners. TNF-alpha-induced ICAM-1 surface and gene expression were both blocked by the RNA polymerase II inhibitor actinomycin D (0.1 microg/ml), and surface expression was attenuated by a neutralizing monoclonal antibody directed against the TNF-alpha receptor p55 (TNF-RI). The intracellular signaling pathway leading to enhanced expression appeared to involve activation of a phospholipase C that hydrolyzes phosphatidylcholine (PC-PLC) because D609, a specific PC-PLC inhibitor, attenuated TNF-alpha-induced increases in production of diacyl-glycerol (DAG), a hydrolysis product of PC-PLC, and also attenuated TNF-alpha enhancement of ICAM-1 surface and gene expression. Because DAG formed by action of PC-PLC can activate protein kinase C (PKC), involvement of PKC was investigated. The specific PKC inhibitor calphostin C blocked both surface and gene expression of ICAM-1 in response to TNF-alpha in a concentration-dependent manner. Finally, TNF-alpha stimulated binding of p65 and/or c-rel complexes to the nuclear factor (NF)-kappaB consensus binding site found on the ICAM-1 promoter, and binding of these complexes was inhibited by D609. The results support the following pathway, whereby TNF-alpha enhances expression of ICAM-1 in NHBE cells: TNF-alpha --> TNF-RI --> PC-PLC --> DAG --> PKC --> (NF-kappaB?) --> ICAM-1 mRNA --> ICAM-1 surface expression.

Antibodies, Monoclonal↗

PubMed2000

Nonpeptide tachykinin receptor antagonists. II. Pharmacological and pharmacokinetic profile of SB-222200, a central nervous system penetrant, potent and selective NK-3 receptor antagonist.

The pharmacological and pharmacokinetic profile of SB-222200 [(S)-(-)-N-(alpha-ethylbenzyl)-3-methyl-2-phenylquinoline-4-car boxami de], a human NK-3 receptor (hNK-3R) antagonist, was determined. SB-222200 inhibited (125)I-[MePhe(7)]neurokinin B (NKB) binding to Chinese hamster ovary (CHO) cell membranes stably expressing the hNK-3 receptor (CHO-hNK-3R) with a K(i) = 4.4 nM and antagonized NKB-induced Ca(2+) mobilization in HEK 293 cells stably expressing the hNK-3 receptor (HEK 293-hNK-3R) with an IC(50) = 18.4 nM. SB-222200 was selective for hNK-3 receptors compared with hNK-1 (K(i) > 100,000 nM) and hNK-2 receptors (K(i) = 250 nM). In HEK 293 cells transiently expressing murine NK-3 receptors (HEK 293-mNK-3R), SB-222200 inhibited binding of (125)I-[MePhe(7)]NKB (K(i) = 174 nM) and antagonized NKB (1 nM)-induced calcium mobilization (IC(50) = 265 nM). In mice oral administration of SB-222200 produced dose-dependent inhibition of behavioral responses induced by i.p. or intracerebral ventricular administration of the NK-3 receptor-selective agonist, senktide, with ED(50) values of approximately 5 mg/kg. SB-222200 effectively crossed the blood-brain barrier in the mouse and rat. The inhibitory effect of SB-222200 against senktide-induced behavioral responses in the mouse correlated significantly with brain, but not plasma, concentrations of the compound. Pharmacokinetic evaluation of SB-222200 in rat after oral administration (8 mg/kg) indicated sustained plasma concentrations (C(max) = about 400 ng/ml) and bioavailability of 46%. The preclinical profile of SB-222200, demonstrating high affinity, selectivity, reversibility, oral activity, and central nervous system penetration, suggests that it will be a useful tool compound to define the physiological and pathophysiological roles of NK-3 receptors, in particular in the central nervous system.

Animals↗