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Biomedical subjects

J Jones

Publications and source records attributed to J Jones.

At least 19 recordsLinked to original sources
PubMed1992

Escherichia coli genes involved in cell survival during dormancy: role of oxidative stress.

When Escherichia coli cells reach stationary phase of growth, specific gene products are synthesized that protect cells while dormant. "Aged" cells may remain viable in cultures for years. For example, agar cultures stored for 38 years still had more than 10(5) viable cells/ml. However, when specific mutants were cultured, the population of these mutants dropped sharply after 4-10 days. This defect is termed "Stationary-Phase-Death". Each mutant strain was hypersensitive to near-ultraviolet radiation and other oxidative agents. Bovine catalase rescued many of the mutants from death in dormancy, suggesting that specific gene products protect "aged" cells against oxidative damage.

Escherichia coli↗
PubMed1992

Identification and characterization of columbid annexin Icp37. Insights into the evolution of annexin I phosphorylation sites.

Annexin I (AnxI) contains phosphorylation sites in its "hinge region" that have been implicated in the regulation of cell growth and/or differentiation. A pigeon (Columba livia) isoform of this protein, annexin Icp35 (cp35), has a very similar amino acid sequence overall but an unrelated sequence that lacks phosphorylation sites in the hinge region. We now report the identification and characterization of annexin Icp37 (cp37) from pigeon. Genomic cloning and Southern blot analysis demonstrated that cp37 and cp35 were encoded by separated genes. Prolactin induced the expression of cp35 mRNA but not cp37. The amino acid sequence of cp37 was deduced from a cDNA clone and found to share 93 and 75% sequence identity with cp35 and human AnxI, respectively. The amino acid sequence of cp37 bore similarities to both AnxI and cp35 in the critical hinge region. Like AnxI, cp37 contained consensus phosphorylation sites in its amino acid sequence and was phosphorylated on tyrosine by the EGF receptor/kinase and on serine by protein kinase C in vitro. Despite the functional similarities between cp37 and AnxI, the nucleotide sequence that encoded the hinge region of cp37 was very similar to the analogous region of cp35, but different from that of AnxI. We propose that certain features shared by cp37 and AnxI are the products of convergent evolution. The fact that evolution independently selected for two annexin I-like genes (cp37 and anxI) encoding analogous phosphorylation sites is strong evidence that phosphorylation is important for the regulation of the biological activity of these proteins.

Amino Acid Sequence↗
PubMed1992

Interstitial deletion 8p21.3----p23.1 in a 6-year-old girl.

We present a 6-year-old mentally retarded girl. Chromosome analysis showed an interstitial deletion of chromosome 8; 46,XX,del(8) (pter----p23.1::p21.3----qter). The proposita had normal activities of glutathione synthetase reductase (GSR) and factor VII. Parental chromosomes were normal.

Child↗
PubMed1992

Inhibition of protein kinase C by annexin V.

Annexin V is a protein of unknown biological function that undergoes Ca(2+)-dependent binding to phospholipids located on the cytosolic face of the plasma membrane. Preliminary results presented herein suggest that a biological function of annexin V is the inhibition of protein kinase C (PKC). In vitro assays showed that annexin V was a specific high-affinity inhibitor of PKC-mediated phosphorylation of annexin I and myosin light chain kinase substrates, with half-maximal inhibition occurring at approximately 0.4 microM. Annexin V did not inhibit epidermal growth factor receptor/kinase phosphorylation of annexin I or cAMP-dependent protein kinase phosphorylation of the Kemptide peptide substrate. Since annexin V purified from both human placenta and recombinant bacteria inhibited protein kinase C activity, it is not likely that the inhibitor activity was associated with a minor contaminant of the preparations. The following results indicated that the mechanism of inhibition did not involve annexin V sequestration of phospholipid that was required for protein kinase C activation: similar inhibition curves were observed as phospholipid concentration was varied from 0 to 800 micrograms/mL; the extent of inhibition was not significantly affected by the order of addition of phospholipid, substrate, or PKC, and the core domain of annexin I was not a high-affinity inhibitor of PKC even though it had similar Ca2+ and phospholipid binding properties as annexin V. These data indirectly indicate that inhibition occurred by direct interaction between annexin V and PKC. Since the concentration of annexin V in many cell types exceeds the amounts required to achieve PKC inhibition in vitro, it is possible that annexin V inhibits PKC in a biologically significant manner in intact cells.

Annexin A5↗
PubMed1992

Chemotaxis of metastatic tumor cells: clues to mechanisms from the Dictyostelium paradigm.

Amoeboid movement, and in some cases, amoeboid chemotaxis, is a key step in tumor metastasis. The high degree of conservation in signal transduction pathways and motile machinery in eukaryotic cells suggests that insights and molecular probes developed from the study of these processes in easily manipulated experimental model systems will be applicable directly to experimentally intractable tumor cells. One such model system, Dictyostelium discoideum, is discussed in terms of the molecular events involved in amoeboid chemotaxis. The application of insights and assays developed with Dictyostelium to early events in the chemotaxis of Lewis lung carcinoma cells is reviewed.

Actins↗
PubMed1992

Prevention of hyperbaric-associated middle ear barotrauma.

STUDY OBJECTIVE: To determine the efficacy of topical nasal decongestant in the prevention of middle ear barotrauma in patients undergoing hyperbaric oxygen therapy. DESIGN: Prospective, parallel, double-blind, randomized trial. SETTING: University-affiliated community hospital emergency department with hyperbaric oxygen facilities. PARTICIPANTS: Sixty patients undergoing hyperbaric oxygen therapy; 30 subjects in each treatment arm. INTERVENTIONS: After randomization, consenting patients were given two sprays of oxymetazoline hydrochloride or sterile water, 15 minutes before hyperbaric oxygen therapy. Collected data included patient demographics, ear examinations before and after hyperbaric oxygen treatment, and subjective ear complaints. The otoscopic appearance of the tympanic membrane was graded according to the amount of hemorrhage in the eardrum, with Teed scores ranging from 0 (symptoms only) to 5 (gross hemorrhage and rupture). RESULTS: The treatment groups were similar with regard to age, sex, and medical history. Ear discomfort during hyperbaric oxygen therapy was present in 63% (19 of 30) of those receiving oxymetazoline versus 67% (20 of 30) of the control group (P = .99). Likewise, both groups had similar Teed scores after hyperbaric oxygen therapy (P = .88). No adverse effects were noted. CONCLUSION: The results of this pilot study suggest that topical decongestants may not be effective in preventing middle ear barotrauma during hyperbaric oxygen therapy.

Administration, Topical↗
PubMed1992

Pseudoephedrine for the prevention of barotitis media: a controlled clinical trial in underwater divers.

STUDY OBJECTIVE: To determine the efficacy and safety of decongestant prophylaxis among first-time underwater divers in the prevention of barotitis media (middle ear squeeze). DESIGN: Randomized, double-blind, prospective clinical trial. SETTING: Recreational diving schools in Panama City, Florida. TYPE OF PARTICIPANTS: One hundred twenty volunteer scuba divers under the supervision of certified instructors. INTERVENTIONS: After randomization, each subject received a 60-mg tablet of pseudoephedrine or placebo 30 minutes before diving. Prospective data were collected, including subject demographics, signs and symptoms of middle ear squeeze during the dive, and possible drug side effects. The otoscopic appearance of the tympanic membrane was graded according to the amount of hemorrhage in the eardrum, with Teed scores ranging from 0 (normal) to 5 (gross hemorrhage and rupture). chi 2 and t-tests were applied with significance set at P less than .05). The Mantel-Haenszel test was used to test the null hypothesis that the mean Teed scores of the two treatment groups were equal. RESULTS: A total of 116 subjects met the inclusion criteria and completed the study; 60 received 60 mg pseudoephedrine, and 56 received placebo. The treatment groups were similar with regard to age, sex, medical history, and depth of the first dive (P greater than .5). Ear discomfort and blockage during the dive were present in 8% (five of 60) of those receiving pseudoephedrine versus 32% (18 of 56) of the control group (P = .001). Similarly, the pseudoephedrine group had smaller Teed scores after diving than did the control subjects (P = .003). Adverse effects were minimal; two patients experienced dizziness and nausea. CONCLUSION: These results suggest that the use of an oral decongestant before diving decreases the incidence and severity of middle ear squeeze in novice divers.

Adult↗
PubMed1992

A candidate mouse model for Prader-Willi syndrome which shows an absence of Snrpn expression.

The best examples of imprinting in humans are provided by the Angelman and Prader-Willi syndromes (AS and PWS) which are associated with maternal and paternal 15q11-13 deletions, respectively, and also with paternal and maternal disomy 15. The region of the deletions has homology with a central part of mouse chromosome 7, incompletely tested for imprinting effects. Here, we report that maternal duplication for this region causes a murine imprinting effect which may correspond to PWS. Paternal duplication was not associated with any detectable effect that might correspond with AS. Gene expression studies established that Snrpn is not expressed in mice with the maternal duplication and suggest that the closely-linked Gabrb-3 locus is not subject to imprinting. Finally, an additional new imprinting effect is described.

Animals↗
PubMed1992

Administration of human recombinant insulin-like growth factor-I to patients following major gastrointestinal surgery.

OBJECTIVE: The aim was to study the pharmacokinetic parameters and biological activity of a single dose of human recombinant IGF-I (rhIGF-I) administered to patients following major gastrointestinal surgery. DESIGN: A double blind placebo controlled externally randomized study of 30 patients; the study commencing 24 hours after major colonic or gastric surgery. MEASUREMENTS: After a baseline blood sampling day, IGF-I (40 micrograms/kg by single subcutaneous dose, n = 20) or placebo (n = 10) was administered and serum and urine samples collected over the ensuing 72 hours. Serum IGF-I, IGF-II, IGF binding proteins (IGFBP-1, IGFBP-3), GH and insulin were measured by radioimmunoassay. Serum IGF bioactivity was assessed using a validated porcine cartilage bioassay. Serum and urinary electrolytes were measured by standard methodology. RESULTS: Serum immunoreactive IGF-I levels peaked at 4 hours following injection of IGF-I (1.09 +/- 0.12 U/ml mean +/- SEM), remained elevated for 15 hours and returned to basal levels by 24 hours after injection. IGF bioactivity was increased by 57% 6 hours after IGF-I injection. Mean levels of IGFBP-1 and IGFBP-3, IGF-II and GH were unaffected by IGF-I administration. Insulin levels were suppressed at 30 minutes following injection of IGF-I compared with the placebo group (16.9 +/- 3.0 mU/I vs 32.3 +/- 7.1, P = 0.02); thereafter, there were no differences in insulin levels. The mean change in serum creatinine following IGF-I (-6.3 +/- 3.0 mmol/l) was significantly different from that in the control group (+7.2 +/- 6.2, P = 0.03). Creatinine clearance rose from a mean of 71.6 +/- 7.5 ml/min to 83.2 +/- 7.6 ml/min after IGF-I treatment (P = 0.02). In the IGF treated patients, cholesterol levels consistently fell (-0.20 +/- 0.05 mmol/l); this was not observed in the placebo group (+0.20 +/- 0.14, P = 0.006). Basal serum potassium levels in the IGF treatment group (4.1 +/- 0.1 mmol/l) fell to 3.8 +/- 0.1 at 4 hours (P = 0.002) and 3.6 +/- 0.1 at 10 hours (P = 0.001) returning to a level of 4.0 +/- 0.1 (P = 0.293) at 24 hours after injection. There were no other observed differences in serum or urinary electrolytes or serum free fatty acids and triglycerides. Pharmacokinetic parameters derived from baseline adjusted IGF-I measurements revealed a slow absorption of the administered dose with a Tmax of 5.0 +/- 0.43 hours and an elimination half-life of 10.8 +/- 1.2 hours. The computed volume of distribution was 0.33 +/- 0.05 I/kg and the clearance on average 25 ml/min. CONCLUSION: A single subcutaneous dose of IGF-I normalized circulating IGF-I levels in post-operative patients, was well tolerated and without side-effects. IGF bioactivity was increased and associated with a fall in serum cholesterol, potassium and creatinine levels and a rise in creatinine clearance. Further long-term studies are now required to assess the anabolic effects of rhIGF-I in this type of patient group.

Aged↗
PubMed1992

Guidelines for the use of fresh frozen plasma. British Committee for Standards in Haematology, Working Party of the Blood Transfusion Task Force.

Fresh frozen plasma should only be used to treat bleeding episodes or prepare patients for surgery in certain defined situations. Definite indications for the use of FFP: 1. Replacement of single coagulation factor deficiencies, where a specific or combined factor concentrate is unavailable. 2. Immediate reversal or warfarin effect. 3. Acute disseminated intravascular coagulation (DIC). 4. Thrombotic thrombocytopenic purpura (TTP). Conditional uses: FFP only indicated in the presence of bleeding and disturbed coagulation: 1. Massive transfusion. 2. Liver disease. 3. cardiopulmonary bypass surgery. 4. Special paediatric indications. No justification for the use of FFP: 1. Hypovolaemia. 2. Plasma exchange procedures. 3. 'Formula' replacement. 4. Nutritional support. 5. Treatment of immunodeficiency states.

Adult↗
PubMed1992

Estimation of erythropoietin secretion rate in normal and uremic subjects.

We have developed a method for directly estimating the secretion rate of endogenous erythropoietin (EPO) in human subjects. Carrier-free recombinant human EPO was labeled with 125I by the chloramine T method. Human serum albumin was then added prior to removal of free iodide. Seven normal subjects and nine patients with chronic uremia and anemia were studied. Each subject received a bolus of 125I-EPO according to body size and then a constant infusion for 5 h. Secretion rate was calculated as the rate of infusion divided by serum EPO specific activity given by the protein-bound counts divided by the EPO concentration. Serum EPO concentration was significantly higher in the patients than the controls (mean 30.9 pg/ml vs. 11.1 pg/ml, P < 0.05), although all values were within the normal range. Mean EPO secretion rate was 255 in the patients (range 68-1,101) and 190 pg.kg-1 x h-1 in the normal group (range 52-382). This difference was not significant. As the subjects were in a steady state, EPO disappearance/degradation was the same in patients compared with controls despite a relatively hypoplastic marrow.

Adult↗
PubMed1992

Detection of HIV-1 protein and nucleic acid in enterochromaffin cells of HIV-1-seropositive patients.

Diarrhea contributes significantly to the morbidity and mortality of patients with the acquired immunodeficiency syndrome (AIDS). Up to 50% of AIDS patients have diarrhea, and an etiologic agent for this cannot be identified in all of them. Recent evidence suggests that enterochromaffin cells may be infected by the human immunodeficiency virus type 1 (HIV-1) and may contribute to the unexplained diarrhea. To test this hypothesis further, endoscopic biopsies of duodena from 22 HIV-1 seropositive patients [17 with diarrhea (> 500 g/day and > 3 bowel movements/day), five without diarrhea] and from 15 normal controls (no HIV risk factors) without diarrhea were studied. Formalin-fixed and paraffin-embedded 5-microns sections were examined by immunocytochemistry, using a monoclonal antibody to the HIV-1 gp41 protein, and by in situ hybridization with a full-length biotinylated HIV-1 DNA probe. Positive staining for gp41 was detected in crypt cells, consistent with the location, size, and morphology of enterochromaffin cells, in 11 of 17 HIV-1-seropositive patients with diarrhea, and in none of five without diarrhea. Nucleic acid hybridization staining was performed in five of the 11 patients who had positive gp41 staining; all showed HIV nucleic acid sequences in similar cells. All three of the five patients with positive staining for HIV nucleic acid sequences had diarrhea for which no etiologic agent for diarrhea could be found, and one each had cryptosporidia or microsporidia. No staining was observed in any of the samples from normal control tissues. These results suggest that HIV-1 may infect enterochromaffin cells and possibly alter their function. This, in turn, may contribute to the diarrhea associated with AIDS.

Adult↗
PubMed1992

Risk factors for coronary heart disease in a black population.

A matched case control study using population-based controls was done over a 2-year period in an urban, public hospital setting. The object of the study was to determine if the established risk factors for coronary heart disease--hypertension, diabetes mellitus, hypercholesterolemia, cigarette smoking, low socioeconomic status (as reflected by occupational class and educational level), marital status, and obesity were associated with coronary heart disease in a black population. The established risk factors were found to be significant in this patient population, as was obesity. Being divorced or separated was a risk factor for women but not for men.

Black or African American↗
PubMed1992

Performance of proficiency survey samples in two immunoradiometric assays of human growth hormone and comparison with patients' samples.

The immunoradiometric assay (IRMA) used in our laboratory for the measurement of growth hormone (hGH; somatotropin) performed badly in the national proficiency survey program, the U.K. External Quality Assessment Scheme (EQAS). We compared our assay with another IRMA, which gave similar results for patients' samples and performed adequately in EQAS. The samples from EQAS are collected from patients with polycythemia and fall into two categories: those containing endogenous hGH and those supplemented with pituitary-derived hGH. Analysis of the two groups separately showed that the differences between the two IRMAS were in the measurement of the endogenous hormone. The reason for this appears to be a matrix effect related to the fact that the EQAS serum samples are collected from polycythemic patients.

Growth Hormone↗
PubMed1992

What will happen to the quality of care with fewer junior doctors? A Delphi study of consultant physicians' views.

Hospital medical staffing: achieving a balance proposed a reduction in the number of junior doctors and an expansion in the number of consultant posts. This change was to be subject to the 'safety net'--that the number of staff should not fall below a minimum safe level for 24-hour emergency cover. However, no operational definition of 'safe' was offered. Consultant physicians in one NHS region were interviewed to find out how they thought safety would be affected by a reduction in junior doctor numbers. It emerged that consultants' concerns over reductions in staff covered a wider range of issues than just the clinical effectiveness of care. The interpretation of safety extended to cover general adverse effects on care. A survey, using the Delphi method, revealed that consultant physicians were most concerned over reductions in the humanity of care if numbers of junior staff were reduced. This included such factors as the time spent by patients waiting in outpatient and A&E departments, and the time doctors spend talking to patients. Consultants were less concerned over the effect of reduced staff numbers on the technical efficiency of provision, and least of all on the effectiveness of care. This last point was seen to be a reflection of consultant physicians' confidence in the basic medical knowledge and skill of their junior staff.

Attitude of Health Personnel↗