Search PubMed⌕ Search

Biomedical subjects

J B Jones

Publications and source records attributed to J B Jones.

At least 91 records · Page 5Linked to original sources
PubMed1990

Conversion disorder. Camouflage for brain lesions in two cases.

We present two cases of serious central nervous system disease initially misdiagnosed as conversion disorder. In each instance, multiple medical evaluations did not uncover the underlying neurologic disorder. Skepticism on the part of psychiatric evaluators led to eventual diagnosis. Common difficulties in the clinical application of the diagnostic criteria for conversion disorder are discussed in relation to the specific pitfalls of the two cases. We make recommendations to aid in the evaluation of suspected cases of conversion disorder.

Brain Neoplasms↗
PubMed1990

Synchrony of bone marrow proliferation and maturation as the origin of cyclic haemopoiesis.

Cyclic haemopoiesis in Grey Collie dogs is characterized by stable oscillations in all haemopoietic lineages. It is proposed that in these animals, in contrast to normal animals, the maturation process of haemopoietic (in particular granuloid) cells from the primitive progenitors to the functional cells is characterized by an abnormally strong synchrony. It is conjectured that the marrow maturation time has a very small variance compared with non-cyclic normal dogs. With a mathematical model of haemopoiesis it is shown that small fluctuations are amplified via regular feedback processes such that stable granuloid oscillations are established. Erythroid oscillations are induced indirectly by granuloid feedback to the stem cell pool. The model calculations further show that the synchrony hypothesis of bone marrow maturation can quantitatively explain the following experimental results: (1) the maintenance of stable cycles of granuloid and erythroid bone marrow and blood cells with a period of approximately 14 d; (2) the disappearance of granuloid and erythroid cycles during the administration of the colony stimulating factor rhG-CSF; (3) the reappearance of oscillations when the administration of CSF is discontinued; (4) the cessation of cycles during endotoxin application; and (5) the persistence of cycles during erythroid manipulations (bleeding anaemia, hypoxia, hypertransfusion). We therefore conclude that cyclic haemopoiesis is not caused by a defect in the regulatory control system but by an unusual maturation process.

Animals↗
PubMed1990

Radioprotective effect of free radical scavenging enzymes.

Ionizing radiation is an important treatment modality in the management of head and neck squamous cell carcinoma. The superoxide (O2-) and hydroxyl (OH.) radicals produced from oxygen and the radio-hydrolysis of water are responsible for most of the DNA and lipid membrane injury caused by radiotherapy. Superoxide dismutase (SOD) and catalase (CAT) are intracellular enzymes that scavenge the superoxide and hydroxyl radicals respectively. The effect of intravenous SOD and CAT on acute and delayed radiation injury was investigated in a rat model. Catalase was shown to reduce the severity of radiation-induced changes in both the vascular endothelium and squamous epithelium. SOD, alone or with CAT, showed no radioprotective effect. As intravenous catalase does not penetrate intracellularly it should have no effect on the tumoricidal effect of radiation. Further investigation of catalase as an agent to reduce the acute side-effects of radiotherapy is warranted.

Animals↗
PubMed1990

Increased efficiency of gene transfer with retroviral vectors in neonatal hematopoietic progenitor cells.

The retroviral vector N2, which is derived from the Moloney murine leukemia retrovirus, was used to transfer the bacterial NeoR gene (conferring resistance to the neomycin analogue G418) into hematopoietic progenitor cells from fetal, neonatal, and adult dogs and cats. Infection of canine and feline bone marrow cells with the N2 vector resulted in resistance of granulocyte-macrophage colony-forming units (CFU-GM) to G418. Approximately 2%-4% of fetal liver, fetal bone marrow, and adult bone marrow day-7 CFU-GM were resistant to 1.75 mg/ml G418, a dose toxic to cells not expressing the NeoR gene, after infection with the N2 retrovirus. In sharp contrast to the low rate of infectivity of both fetal and adult marrow samples, the mean +/- SD of G418-resistant CFU-GM was 11.7% +/- 14.1% and 14.0% +/- 18.1% for neonatal dog and cat marrow samples, respectively. The neomycin phosphotransferase enzyme activity was detected in G418-resistant CFU-GM, confirming that G418-resistant CFU-GM expressed the NeoR gene. The increased efficiency of retroviral vector-mediated gene transfer into neonatal hematopoietic progenitor cells was not due to an increased fraction of actively dividing cells, as determined by tritiated thymidine suicide. Understanding the basis for increased gene transfer into neonatal hematopoietic progenitor cells may be helpful in designing effective retroviral vectors/gene transfer protocols for gene therapy.

Animals↗
PubMed1989

On the effects of replacing the carboxylate-binding arginine-171 by hydrophobic tyrosine or tryptophan residues in the L-lactate dehydrogenase from Bacillus stearothermophilus.

For L-lactate dehydrogenases (LDH's), the interaction of the guanidinium group of their Arg 171 residue with the carboxylate group of an alpha-keto acid is of primary importance in orienting the substrate productively at the active site. LDH's such as that of Bacillus stearothermophilus (BSLDH) are of practical importance for the preparation of chiral 2-hydroxy acids used as synthons in asymmetric synthesis but would even be more valuable in this regard if their specificities were broader. With a view to tailoring the specificity of BSLDH toward carbonyl substrates that lack an alpha-carboxyl group such as ketones, site-directed mutagenesis has been applied to replace Arg 171 by the approximately isosteric, but hydrophobic, amino acids Tyr and Trp. The mutant enzymes exhibit remarkably good catalytic activities toward representative alpha-keto acids RCOCOOH, where R = Me, Et, n-Pr, n-Bu, and CH2OH, although for the mutant enzymes the kcat/KM's are lower by approximately 10(3)-10(4)-fold than those for native BSLDH. Surprisingly, the 171----Tyr/Trp enzymes are significantly more active than 171----Lys (Hart et al., 1987a), for which an interaction of a positively charged side chain with substrate COO- is retained. Preparative-scale 171----Trp catalyzed reduction of pyruvate gave optically pure L-lactate, showing that L stereospecificity of such LDH enzymes was unaffected by the loss of Arg 171. The retention of L stereospecificity is attributed to secondary polar or hydrogen-bonding associations of Arg 109 and Thr246, respectively, with the substrate COO-function that are of sufficient magnitude to maintain "normal" substrate orientation.(ABSTRACT TRUNCATED AT 250 WORDS)

Arginine↗
PubMed1989

On the effect on specificity of Thr246----Gly mutation in L-lactate dehydrogenase of Bacillus sterothermophilus.

The function of the amino acid Thr246 in L-lactate dehydrogenase from Bacillus stearothermophilus has been investigated by site-directed replacement with glycine. Kinetic experiments with a number of 2-oxo acids showed strongly reduced activity for the mutated enzyme. However, the mutant enzyme shows a relative preference for the large hydrophobic sidechains of alpha-keto acids and an even higher specific activity than the wild-type lactate dehydrogenase for the polar oxaloacetate substrate. Graphic analyses indicate that the loss of one hydrogen bond, or intrusion of water into the active site, might be responsible for the reduced activity. The kinetic results suggest that the binding modes of bulky hydrophobic or polar substrates compensate to some degree for the partially disrupted active site.

Amino Acid Sequence↗
PubMed1989

Drug-induced esophageal injury: a case report of percogesic.

This is the first case report of esophageal injury caused by Percogesic. A 31-year-old healthy white woman presented with dysphagia and retrosternal pain following the ingestion of a Percogesic tablet. The patient felt the tablet lodge in her mid-esophagus even though she ingested it with a cupful of water and in the upright position. Additional fluid was taken to dislodge the tablet with no success. Past medical history was unremarkable for heartburn, regurgitation, or dysphagia. Upper gastrointestinal endoscopy revealed a well-circumscribed deep ulceration in the mid-esophagus. Hospitalization was required due to persistent dysphagia. Treatment consisted of a three-day regimen of liquid antacid, intravenous ranitidine hydrochloride, and metoclopramide. This case emphasizes that pill entrapment can occur in the esophagus in healthy individuals, even when taken in the upright position with plenty of fluid; and mucosal injury can be produced by drugs not generally reported to cause gastrointestinal adverse effects or mucosal injury.

Acetaminophen↗
PubMed1989

Misoprostol: a prostaglandin E1 analog with antisecretory and cytoprotective properties.

Misoprostol, a methylester analog of prostaglandin E1, with antisecretory and cytoprotective properties, has undergone extensive investigation and has received Food and Drug Administration approval for the prevention of nonsteroidal-induced ulceration. The drug represents the first synthetic, orally active prostaglandin evaluated for the treatment of peptic ulcer disease. Clinical studies reveal a trend toward slightly lower healing rates with misoprostol when compared with histamine (H2)-receptor antagonists in the treatment of gastric and duodenal ulcers. In addition, misoprostol was less effective than H2-blockers in reducing ulcer pain, and caused a higher incidence of adverse reactions, particularly diarrhea occurring in up to 13 percent of the patients treated. Several studies have shown misoprostol to be superior to cimetidine and sucralfate in the prevention of alcohol- and drug-induced gastritis. This report summarizes the biopharmaceutics, pharmacokinetics, and clinical efficacy of misoprostol in the treatment of gastric and duodenal ulcers and in the prevention of mucosal injury.

Alprostadil↗
PubMed1989

Surface morphology and ultrastructure of normal and cyclic hematopoietic canine bone marrow in long-term liquid cultures.

Long-term liquid cultures of normal and cyclic hematopoietic (CH) dog bone marrow produce committed granulocyte-macrophage progenitor cells (CFU-GM) and differentiated granulocytes for several weeks. Analysis of in situ fixed cultures or of cells harvested from the culture supernatants revealed that the cells had ultrastructure and surface morphology characteristic of immature and mature myeloid cells. The surface morphologies of adherent cells from both normal and CH dogs were similar. The characteristic abnormalities previously reported in neutrophils obtained from CH dogs were not observed in neutrophils obtained from long-term marrow cultures of CH dogs. These results indicate that the cellular abnormalities in the neutrophils of CH dogs may be secondary manifestations of the disease and are not inherent to the pathogenesis of the hematopoietic cells.

Animals↗
PubMed1989

Effect of canine parvovirus on erythroid progenitors in phenylhydrazine-induced regenerative hemolytic anemia in dogs.

The effects of canine parvovirus (CPV) infection in dogs with hemolytic anemia was compared with the clinical effects of human parvovirus-induced aplastic anemia in human beings with chronic regenerative anemias. Phenylhydrazine was used to induce a transient, severe, hemolytic anemia in dogs to evaluate the effects of CPV infection on rapidly dividing bone marrow precursors. Erythrocyte colony-forming unit bone marrow cultures and cytologic examination of bone marrow were used to determine the effects of CPV infection on erythroid bone marrow precursors. The induced hemolytic anemia regenerated rapidly and although the bone marrow was infected, it was determined that CPV infection did not induce a detectable decrease in erythroid progenitors in dogs with severe hemolytic anemia.

Anemia, Aplastic↗
PubMed1989

Carcinoma of the tongue in young patients.

Carcinoma of the tongue is the second most common malignancy of the oral cavity, predominantly affecting males in the sixth and seventh decades of life. The risk factors for this disease (primarily tobacco and ethanol abuse) are well documented in the literature. The current five-year survival for a T1 lesion without nodal involvement is approximately 80%. Over the past 10 years a group of younger patients (less than 40 years) has been identified. Eleven of these patients presenting to the London Regional Cancer Centre since 1976 are reviewed with respect to stage at diagnosis, known risk factors, and the outcome of treatment. Comparison is then made with a similar group of older (over 40 years) patients. The previously identified risk factors, and the male/female ratio are quite different from the older patients. This younger group would appear to have a biologically more aggressive tumor than the stage (TNM) at presentation would suggest. They require more complex treatment, frequently requiring major resections plus radiotherapy for what appears to be early disease. The role for more aggressive initial therapy must be considered.

Adult↗
PubMed1988

Correction of canine cyclic hematopoiesis with recombinant human granulocyte colony-stimulating factor.

Canine cyclic hematopoiesis (CH) is an autosomal recessive disease of gray collie dogs that is characterized by neutropenic episodes at 14-day intervals. The biochemical basis for CH is not known but may involve a regulatory defect of the response to or production of a hematopoietic growth factor. Administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) to two CH and one normal dog caused a marked leukocytosis (greater than 50,000 WBCs) in all three dogs. The leukocytosis was due largely to a greater than tenfold increase in neutrophils. Less pronounced but significant elevations in monocytes occurred during G-CSF treatment. The elevated WBC count was maintained for more than 20 days in all three dogs, and two predicted neutropenic episodes were prevented in both CH dogs during rhG-CSF treatment. A decline in the WBC count occurred simultaneously in all three dogs during the last five treatment days and was presumably associated with the development of neutralizing antibodies to the heterologous rhG-CSF protein. Bone marrow evaluation indicated that the swings in the myeloid/erythroid progenitor cells that are characteristic of CH were eliminated by rhG-CSF treatment in both CH dogs. These results suggest that the regulatory defect in canine CH can be temporarily alleviated by treatment with rhG-CSF and point to the potential treatment of human cyclic neutropenia with this agent.

Agranulocytosis↗
PubMed1988

Gene transfer into hematopoietic progenitor cells from normal and cyclic hematopoietic dogs using retroviral vectors.

The Moloney murine leukemia retrovirus-derived vector N2 was used to transfer the bacterial NeoR gene (conferring resistance to the neomycin analogue G418) into hematopoietic progenitor cells. Approximately 5% of day seven CFU-GM were resistant to 2,000 micrograms/ml G418, using a supernatant infection protocol in the absence of vector-producing cells. A greater proportion of CFU-GM colonies were recovered relative to uninfected controls as the stringency of selection was diminished. Enzyme activity was detected in drug-resistant colonies, confirming that the resistant colonies obtained after infection with N2 represented cells producing neomycin phosphotransferase. Activity in the CFU-GM colonies approached 50% of that of drug-resistant vector-producing cells on a per cell basis. To test the hypothesis that more rapidly cycling bone marrow cells would be more susceptible to vector infection, we treated progenitor cells obtained from cyclic hematopoietic (CH) dogs with the N2 vector. Despite the increased numbers of hematopoietic progenitor cells obtained from CH dogs, the proportion of G418-resistant CFU-GM did not increase over that obtained with N2-infected normal marrow. These results demonstrate that retroviral vectors can be used to transfer and express exogenous genes in canine hematopoietic progenitor cells.

Animals↗
PubMed1987

Fixed minidose warfarin: a new approach to prophylaxis against venous thrombosis after major surgery.

A prospective study was carried out to see whether a small fixed dose of warfarin (1 mg daily) given before operation (mean 20 days) would prevent deep vein thrombosis in patients having major gynaecological surgery. One hundred and four patients were randomised into three groups: fixed minidose warfarin; full dose oral anticoagulation; and no treatment (controls). There was a significantly lower incidence of deep vein thrombosis in the minidose warfarin and full dose anticoagulant treatment groups (9% (3/32) and 3% (1/35) respectively) than in the controls (30%; 11/37) but no significant difference between the two anticoagulant treatment groups. Prothrombin time and the activated partial thromboplastin time were normal on the day of surgery in the warfarin treatment group, whereas times were prolonged in the group given full dose anticoagulation. Mean haemoglobin concentrations fell in all three groups after operation but the fall was significantly less in the minidose warfarin treatment group than after full dose anticoagulation. The benefit from full dose oral anticoagulant prophylaxis, based on a preoperative international normalised ratio of 1.5-2.5 with rabbit brain Manchester reagent, was similar to the protection achieved in an oral anticoagulant treatment group controlled with human brain Manchester comparative reagent at a similar level of anticoagulation. The lack of disturbance of normal haemostasis at the time of operation together with a significant reduction in deep vein thrombosis may encourage surgeons to introduce minidose prophylaxis with warfarin.

Adult↗
PubMed1987

A strong carboxylate-arginine interaction is important in substrate orientation and recognition in lactate dehydrogenase.

Using site-directed mutagenesis, Arginine-171 at the substrate-binding site of Bacillus stearothermophilus, lactate dehydrogenase has been replaced by lysine. In the closely homologous eukaryotic lactate dehydrogenase, this residue binds the carboxylate group of the substrate by forming a planar bifurcated bond. The mutation diminishes the binding energy of pyruvate, alpha-ketobutyrate and alpha-ketovalerate (measured by kcat/Km) by the same amount (about 6 kcal/mol). For each additional methylene group on the substrate, there is a loss of about 1.5 kcal/mol of binding energy in both mutant and wild-type enzymes. From these parallel trends in the two forms of enzyme, we infer that the mode of productive substrate binding is identical in each, the only difference being the loss of a strong carboxylate-guanidinium interaction in the mutant. In contrast to this simple pattern in kcat/Km, the Km alone increases with substrate-size in the wild-type enzyme, but decreases in the mutant. These results can be most simply explained by the occurrence of relatively tight unproductive enzyme-substrate complexes in the mutant enzyme as the substrate alkyl chain is extended. This does not occur in the wild-type enzyme, because the strong orienting effect of Arg-171 maximizes the frequency of substrates binding in the correct alignment.

Arginine↗
PubMed1987

Hematological measurements in rats flown on Spacelab shuttle, SL-3.

Previous studies have shown that a decrease in red cell mass occurs in astronauts, and some studies indicate a leukocytosis occurs. A life science module housing young and mature rats was flown on shuttle mission Spacelab 3 (SL-3), and the results of hematology studies of flight and control rats are presented. Statistically significant increases in the hematocrit, red blood cell counts, and hemoglobin determinations, together with a mild neutrophilia and lymphopenia, were found in flight animals. No significant changes were found in bone marrow and spleen cell differentials or erythropoietin determinations. Clonal assays demonstrated an increased erythroid colony formation of flight animal bone marrow cells at erythropoietin doses of 0.02 and 1.0 U/ml but not 0.20 U/ml. These results agree with some but vary from other previously published studies. Erythropoietin assays and clonal studies were performed for the first time.

Animals↗