Search PubMed⌕ Search

Biomedical subjects

C M Jones

Publications and source records attributed to C M Jones.

At least 73 records · Page 4Linked to original sources
PubMed1995

Reasoning about curvilinear motion: using principles or analogy.

People possess implicit theories about the motion of objects, theories that are often incorrect. When asked to predict the path of an object emerging from a curved tube, for example, people often say that the object will continue to follow a curved path. However, when solving a problem that reminds them of a familiar previous instance, people often reason by analogy to the instance. In this study, we show that a previous instance must be very superficially similar to a problem in order to be used as an analogy; otherwise, people will use their implicit theories as the basis of their reasoning.

Adult↗
PubMed1994

Conformational relaxation and ligand binding in myoglobin.

Absorption spectroscopy with nanosecond time resolution shows that myoglobin undergoes conformational relaxation on the same time scale as geminate rebinding of carbon monoxide. Ligand rebinding following photodissociation of the heme-CO complex was measured from the amplitude of the average difference spectrum, while conformational changes were measured from changes in the detailed shape of the Soret spectra of the deoxyhemes. Experiments in which the solvent viscosity was varied between 1 and 300 cP and the temperature between 268 and 308 K were analyzed by fitting the multiwavelength kinetic data with both empirical and molecular models. Novel numerical techniques were employed in fitting the data, including the use of singular value decomposition to remove the effects of temperature and solvent on the spectra and of a Monte Carlo method to overcome the multiple minimum problem in searching parameter space. The molecular model is the minimal model that incorporates all of the major features of myoglobin kinetics at ambient temperatures, including a fast and slow rebinding conformation and two geminate states for each conformation. The results of fitting the kinetic data with this model indicate that the geminate-rebinding rates for the two conformations differ by at least a factor of 100. The differences between the spectra of the two conformations generated from the fits are similar to the differences between those of the R and T conformations of hemoglobin. In modeling the data, the dependence of the rates on temperature and viscosity was parametrized using a modification of Kramers theory which includes the contributions of both protein and solvent to the friction. The rate of the transition from the fast to the slow rebinding conformation is found to be inversely proportional to the viscosity when the viscosity exceeds about 30 cP and nearly viscosity independent at low viscosity. The viscosity dependence at high viscosities suggests that the two conformations differ by the global displacement of protein atoms on the proximal side of the heme observed by X-ray crystallography. We suggest that the conformational change observed in our experiments corresponds to the final portion of the nonexponential conformational relaxation recently observed by Anfinrud and co-workers, which begins on a picosecond time scale. Furthermore, extrapolation of our data to temperatures near that of the solvent glass transition suggests that this conformational relaxation may very well be the one postulated by Frauenfelder and co-workers to explain the decrease in the rate of geminate rebinding with increasing temperature above 180 K.

Animals↗
PubMed1994

Synthetic macrophage activating peptides derived from the N-terminus of human MCF.

Recently, we described the purification and N-terminal sequencing of a novel cytokine termed MCF (Monocyte Cytotoxicity Inducing Factor) (1,2). In order to study the interaction of this cytokine with monocytes, we synthesized a nona-peptide GAAVLEDSQ corresponding to the N-terminus of MCF: two truncated peptides, GAAVL and LEDSQ; and the substituted peptide, GAAVLENSQ. The authentic N-terminal peptide is biologically active in the nanomolar range, while substitution of asparagine for aspartic acid at position 7 diminishes biological activity. Biological activity was observed from the C-terminal fragment LEDSQ, but the N-terminal pentapeptide (GAAVL) was devoid of biological activity. Scatchard analysis revealed a single class of saturable high affinity sites. These studies indicate that the N-terminus of MCF is important in interacting with the binding site on monocytes and it may be possible to design synthetic activators and inhibitors of monocyte/macrophage cytotoxicity.

Amino Acid Sequence↗
PubMed1994

Acute aortic occlusion. A 40-year experience.

OBJECTIVE: To review a large experience with acute aortic occlusion (AAO) to better define the cause, clinical presentation, treatment, prognostic variables, and outcome. DESIGN: Retrospective review of 46 consecutive patients with AAO during a 40-year period. SETTING: A large urban tertiary care referral center in Detroit, Mich. PATIENTS: Adult patients with arteriographic and/or operative confirmation of acute occlusion of the abdominal aorta plus signs and symptoms of acute ischemia. INTERVENTION: Operative and nonoperative treatment of AAO. MAIN OUTCOME MEASURES: Mortality, morbidity, and long-term survival. Other variables measured included cause, risk factors, and effects of duration and severity of ischemia and treatment methods on outcome. RESULTS: Two primary causes were identified--embolism (65%) and thrombosis (35%). Heart disease and female gender were risk factors for embolism, while smoking and diabetes were risk factors for thrombosis. Severity of ischemia on presentation correlated better with outcome than duration of ischemia. The hospital mortality rate was 35% and morbidity, 74%, with no difference between the two groups. Recurrent arterial embolism occurred in 43% of patients with embolic AAO. Seventy-two percent of AAO survivors were alive 5 years after therapy. CONCLUSIONS: Acute aortic occlusion remains a serious vascular surgical emergency with significant morbidity and mortality, even when recognized promptly and treated appropriately. Nevertheless, survivors have a reasonable long-term outcome. Permanent anticoagulation is suggested in patients with embolic AAO to minimize a high incidence of recurrent arterial embolism.

Acute Disease↗
PubMed1994

Degeneracy of T cell receptor recognition of an influenza virus hemagglutinin epitope restricted by HLA-DQ and -DR class II molecules.

DT9301-0229737 the TcR are believed to provide the peptide fragments bound to major histocompatibility (MHC) molecules. TcR have an immunoglobulin (Ig)-like structure and, in an analogous manner to antigen recognition by Ig, the third complementarity determining regions (CDR3) of the TcR are believed to provide the primary contact with the peptide lying in the MHC groove. CDR1 and CDR2 are thought to contact the presenting MHC molecule. We have analyzed seven human CD4+ T cell clones that recognize a conserved peptide epitope (residues 255-270) within the influenza virus hemagglutinin (H3) HA1 subunit. Two T cell clones recognized the peptide in the context of HLA-DRB1*1001 and HLA-DQB1*0602/DQA1*0102, respectively, and shared V alpha, V beta and J beta gene segments. Only the junctional regions encoding the CDR3 regions of the two TcR chains were different. This suggests that the CDR3 regions of these TcR interact with the MHC class II molecule. Six of the T cell clones were restricted by the HLA-DRB1*1001. Two of these T cell clones expressed V beta 9.1 and three expressed V beta 13 gene segments; the remaining clone expressed V beta 7.2, a close homologue of V beta 9.1. A diverse selection of V alpha and J gene segments contributed to the junctional heterogeneity of the TcR, indicating a diversity of sequence combinations recognizing the epitope. Nevertheless, five out of six T cell clones bore a motif in the V alpha CDR3 loop consisting of adjacent acidic and polar amino acid residues, eight residues from the carboxyl end of each CDR3.

Amino Acid Sequence↗
PubMed1994

Embryonic expression of Lim-1, the mouse homolog of Xenopus Xlim-1, suggests a role in lateral mesoderm differentiation and neurogenesis.

cDNAs encoded by the mouse homolog (Lim-1) of the Xenopus LIM-class homeobox gene Xlim-1 have been isolated from an 8.5-day mouse embryo cDNA library. Nucleotide and deduced amino acid sequences show a high degree of identity with Xlim-1 in the LIM and homeodomains, and 85% identity over the whole protein. An interspecific back-cross has been used to show close linkage of Lim-1 to the endogenous proviral marker Mpmv-4 on mouse chromosome 11. Whole mount in situ hybridization studies have been carried out on mouse embryos between 6.5 and 10.5 days. In mid- to late-streak stage embryos, Lim-1 is expressed in a restricted region of mesoderm in the primitive streak, with the highest level of signal at the anterior. At 7.5 days, transcripts can be seen in a horseshoe-shaped pattern in the periphery of the node, as well as along both sides of the immediately adjacent notochord. In addition, transcripts are present in presumptive lateral and intermediate mesoderm. Later, expression becomes progressively restricted to intermediate mesoderm, the nephrogenic cords, and eventually mesonephric ducts and tubules. By 10.5 days Lim-1 transcripts also appear in restricted regions of the central nervous system (CNS) that are associated with sensory function. The lateral diencephalon, hindbrain, and presumed commissural neurons in the dorsal spinal cord all show Lim-1 expression. In the adult, Lim-1 is expressed in the cerebellum/medulla and kidney, and at very low levels in the cerebrum. These data suggest that in the mouse embryo Lim-1 plays a role in early mesoderm formation and later specification of a differentiated phenotype in subsets of cells of the mesonephros and sensory neurons of the CNS.

Amino Acid Sequence↗
PubMed1994

Embryonic expression of mouse bone morphogenetic protein-1 (BMP-1), which is related to the Drosophila dorsoventral gene tolloid and encodes a putative astacin metalloendopeptidase.

cDNAs encoding a mouse gene closely related to human bone morphogenetic protein-1 (BMP-1) have been isolated from an 8.5-day p.c. embryo cDNA library. Analysis of the predicted amino acid sequence shows that the protein contains a putative zinc-binding astacin metalloendopeptidase domain, five Clr/s domains, and two potential Ca(2+)-binding EGF-like repeats. In overall domain organization it more closely resembles the Drosophila tolloid gene product than human BMP-1. By RNase protection, transcripts can be detected in the embryo at 6.5 days p.c. and persist at least until 16.5 days p.c. By in situ hybridization, transcripts are seen at high levels in the maternal deciduum and in the late-gastrulation stage embryo at low levels throughout the mesoderm. This low level of mesodermal expression continues through development but somewhat higher levels are seen in developing membranous and endochondral bone, in the submucosa of the intestine, the dermis of the skin, and the mesenchyme of the spleen and lung. High levels of BMP-1 transcripts are also seen from 9.5 days p.c. in the floorplate region of the developing neural tube. Potential therefore exists for the interaction of BMP-1 protein with products of TGF-beta-related genes expressed during embryogenesis.

Amino Acid Sequence↗
PubMed1994

Human MCF activates monocytes to produce IL-1 but not TNF or CSF-1.

Monocyte cytotoxicity inducing factor (MCF) is a novel cytokine which was originally characterized by its ability to induce monocyte cytotoxicity against tumor targets. The present studies were undertaken to define the mechanisms of cytotoxicity. Since the cytotoxic state may be mediated, in part, by the secretion of monokines, MCF's effect on IL-1, TNF and CSF-1 were measured. MCF caused human peripheral blood monocytes to secrete large amounts of IL-1 but not TNF. In contrast monocytes produce CSF-1 in culture and this production was not enhanced by MCF. IL-1 neither appeared to directly lyse the target K562 nor was able to activate macrophages for cytotoxicity. However, IL-1 may be necessary for lysis of K562 by activated macrophages through its cytostatic effect on K562. MCF increased monocyte surface expression of DR-beta (when studied by fluorescent microfluorometry) and messenger RNA for DR-beta after 24 h in culture. These functional studies indicate that MCF is a cytokine with a distinct spectrum of biologic activities whose functions may be mediated by synthesis and secretion of IL-1.

Cytokines↗
PubMed1994

Acute encephalopathy and status epilepticus associated with human herpes virus 6 infection.

A previously healthy 22-month-old boy presented in status epilepticus with high fever. He was comatose, with upper respiratory-tract infection. The seizures responded to anticonvulsant therapy. The boy's temperature returned to normal within 24 hours and he recovered slowly from his encephalopathy. On the third hospital day, he exhibited the characteristic rash of reseola infantum. Acute infection with human herpes virus 6 (HHV-6) was established serologically by enzyme immunoassay. HHV-6 DNA was not detected by polymerase chain reaction in CSF or serum at the onset of illness, but was found three months later in the child's saliva. The pathogenesis of the patient's encephalopathy is discussed. It is concluded that HHV-6 infection should be considered in infants and young children with febrile status epilepticus.

Comorbidity↗
PubMed1994

Growth factors in development: the role of TGF-beta related polypeptide signalling molecules in embryogenesis.

Embryonic induction, the process by which signals from one cell population influence the fate of another, plays an essential role in the development of all organisms so far studied. In many cases, the signalling molecules belong to large families of highly conserved proteins, originally identified as mammalian growth factors. The largest known family is related to Transforming Growth Factor-beta (TGF-beta) and currently consists of at least 24 different members. Genetic studies in Drosophila on the TGF-beta related gene, decapentaplegic (dpp), reveal the existence of conserved mechanisms regulating both the expression of the protein during development and the way in which it interacts with other signalling molecules to generate pattern within embryonic tissues. Comparative studies on another TGF-beta related gene, known as Bone Morphogenetic Protein-4 (BMP-4), in Xenopus and mouse point to a conserved role in specifying posteroventral mesoderm during gastrulation. Analysis of other polypeptide signalling molecules during gastrulation suggests that their interaction in the generation of the overall body plan has also been conserved during vertebrate evolution.

Animals↗
PubMed1993

Fast events in protein folding initiated by nanosecond laser photolysis.

Initiation of protein folding by light can dramatically improve the time resolution of kinetic studies. Here we present an example of an optically triggered folding reaction by using nanosecond photodissociation of the heme-carbon monoxide complex of reduced cytochrome c. The optical trigger is based on the observation that under destabilizing conditions cytochrome c can be unfolded by preferential binding of carbon monoxide to the covalently attached heme group in the unfolded state. Photodissociation of the carbon monoxide thus triggers the folding reaction. We used time-resolved absorption spectroscopy to monitor binding at the heme. Before folding begins we observe transient binding of both nonnative and native ligands from the unfolded polypeptide on a microsecond time scale. Kinetic modeling suggests that the intramolecular binding of methionine-65 and -80 is faster than that of histidine-26 and -33, even though the histidines are closer to the heme. This optical trigger should provide a powerful method for studying chain collapse and secondary structure formation in cytochrome c without any limitations in time resolution.

Amino Acid Sequence↗
PubMed1993

Dissociation kinetics of actinomycin D from oligonucleotides with hairpin motifs.

The dissociation of 7-aminoactinomycin D (7-AM-ACTD) from d(ATGCATATGCAT), d(ATGCAT-T-ATGCAT), or d(ATGCAT-A-ATGCAT) at 20 degrees C cannot be adequately described by a single-exponential decay and requires a fit with two rate constants. The relative contributions of these two rate processes and their temperature dependence can be attributed to the coexistence of two conformational species in solutions. The slow dissociation rate corresponds to oligonucleotides in the dimeric duplex form, whereas the fast rate occurs with those in the hairpin conformation. The increased relative contribution of the faster component at higher temperatures is consistent with the more favorable thermal stability of the hairpin form. Studies with d(ATGCAT-TTT-ATGCAT) and d(ATGCAT-AAA-ATGCAT), which exist predominantly in the hairpin conformation, indicate that 7-AM-ACTD dissociates from these oligomers single-exponentially with rate constants comparable to or less than those obtained for the dimeric duplex of d(ATGCATATGCAT). Equilibrium binding titrations suggest that ACTD binds to hairpins as strongly as to the related dimeric duplexes, suggesting that the stacking geometry of the G.C base pairs at the dG-dC intercalating site of the hairpin stem is not greatly different from that of the dimeric duplex. The considerable variation in the dissociation rates of 7-AM-ACTD from hairpins, however, reflects the varying degrees of DNA minor-groove distortion of the stem duplex resulting from the hairpin loop formation and consequent interactions with the pentapeptide rings of ACTD. The plausibility of our interpretation is further supported by results from electrophoretic measurements, thermal melting profiles, and additional studies with hairpins containing a CGCG or GCGC stem.

Base Sequence↗
PubMed1993

Photoselection in polarized photolysis experiments on heme proteins.

Polarized photolysis experiments have been performed on the carbon monoxide complex of myoglobin to assess the effects of photoselection on the kinetics of ligand rebinding and to investigate the reorientational dynamics of the heme plane. The results are analyzed in terms of the optical theory developed in the preceding paper by Ansari and Szabo. Changes in optical density arising from rotational diffusion of the photoselected population produce large deviations from the true geminate ligand rebinding curves if measurements are made with only a single polarization. The apparent ligand rebinding curves are significantly distorted even at photolysis levels greater than 90%. These deviations are eliminated by obtaining isotropically-averaged optical densities from measurements using both parallel and perpendicular polarizations of the probe pulse. These experiments also yield the optical anisotropy, which gives a novel method for accurately determining the degree of photolysis, as well as important information on the reorientational dynamics of the heme plane. The correlation time for the overall rotational diffusion of the molecule is obtained from the decay of the anisotropy. The anisotropy prior to rotational diffusion is lower than that predicted for a rigidly attached, perfectly circular absorber, corresponding to an apparent order parameter of S = 0.95 +/- 0.02. Polarized absorption data on single crystals suggest that the decreased anisotropy results more from internal motions of the heme plane which take place on time scales shorter than the duration of the laser pulse (10 ns) than from out-of-plane polarized transitions.

Animals↗
PubMed1993

An evaluation of the total similarity principle: effects of similarity on frequency judgments.

Memory models that embody the total similarity principle (e.g., Gillund & Shiffrin, 1984; Hintzman, 1988; Murdock, 1982; Ratcliff, 1990) assume that frequency judgments reflect the total similarity of a test item to stimuli that have been studied. In 4 experiments, subjects estimated the frequencies of target words that had been presented in the context of varying numbers of semantically similar words. In a fifth experiment, subjects made forced-choice relative frequency judgments. The results of these experiments supported 1 prediction of total similarity models: Presenting similar words will increase rather than decrease frequency judgments of target words. However, a second prediction of these models was not supported. In particular, similar-word presentations had no effect on the judged frequencies of target words that had not been shown.

Adult↗
PubMed1993

Transgenic mice as a model to study the role of TGF-beta-related molecules in hair follicles.

There is increasing evidence that members of the TGF-beta superfamily are important regulators of epithelial growth and differentiation in vivo. Here, transgenic mice have been used to study the role of the TGF-beta-related growth factors BMP-2 and BMP-4 in hair and whisker development. In the mature hair follicle, BMP-2 transcripts are normally seen only in precortex cells at the base of the hair shaft. In the transgenic mice reported here, BMP-4, a closely related molecule, has been ectopically expressed in the outer root sheath of hair and whisker follicles using an expression vector based on the bovine cytokeratin IV* promoter. In response to transgene expression, both outer root sheath cells below the stem cell compartment and hair matrix cells around the dermal papilla cease proliferation. In addition, the expression pattern of cytokeratin markers is disturbed in some transgenic hair follicles. These results support a model in which members of the TGF-beta superfamily play an active role in the inhibiton of cell proliferation and the onset of expression of trichocyte-specific genes that take place when cells leave the matrix of the follicle and differentiate into shaft cells.

Animals↗
PubMed1993

Transforming growth factor beta gene expression is transiently enhanced at a critical stage during liver regeneration after CCl4 treatment.

BACKGROUND: Transforming growth factor beta 1 (TGF beta 1) gene expression is increased in CCl4-injured rat livers. The biologic link of this increase and liver regeneration has not been established. EXPERIMENTAL DESIGN: To explore the identity of the TGF beta 1-producing cells in the CCl4 regenerating liver, we hybridized untreated and CCl4-treated liver sections of TGF beta 1-specific riboprobes and immunolocalized TGF beta 1 protein, simultaneously. To assess the dynamics of cellular proliferation during hepatic regeneration, chronologic changes in the cellular DNA synthesis were also monitored by [3H]thymidine incorporation and autoradiography. In situ hybridization analyses were further extended by subfractionation of nonparenchymal cells into Kupffer cells/macrophages, endothelial and Ito cells, and determining TGF beta 1 mRNA levels in different cell types. Finally, we experimentally tested if the temporal relationship between the transient elevation of expression of TGF beta 1 and hepatic cell proliferation were casually related. RESULTS: We observed that the rate of DNA synthesis was the highest around 36 hours post-treatment and preceded the time of enhanced accumulation of TGF beta 1 transcripts and protein, both of which peaked at approximately 48 hours and declined thereafter. Transient upregulation of TGF beta 1 gene expression was seen in the inflammatory cell infiltrates around the central vein and at less extent, in portal tracts, and in perisinusoidal cells near the zone of necrosis. Like TGF beta 1 transcripts, TGF beta 1 protein was also predominantly co-localized in and around the pericentral and periportal cells. Kupffer cells, that accumulate abundantly in the liver 48 hours after CCl4 administration, were the primary producers of TGF beta 1. The injection of neutralizing anti-TGF beta 1 antibodies into animals prevented both the decline in [3H]thymidine incorporation and cell division in the waning phases of hepatic regeneration at 72 hours. CONCLUSIONS: Based on our observations that (i) TGF beta 1 gene expression is triggered transiently during a crucial phase of liver regeneration, (ii) the exogenously added TGF beta 1 inhibits hepatic DNA synthesis and that (iii) the administration of TGF beta 1 antibodies extends the proliferative response of the regenerating liver, we conclude that TGF beta 1 plays a pivotal role in down regulating liver regeneration.

Animals↗