Search PubMed⌕ Search

Biomedical subjects

P Johnson

Publications and source records attributed to P Johnson.

At least 289 records · Page 16Linked to original sources
PubMed1993

Absence of hepatitis C virus in British patients with type 1 autoimmune chronic active hepatitis--a polymerase chain reaction and serological study.

Despite several studies from continental Europe reporting a high prevalence of antibodies to the hepatitis C virus (HCV), there has been little evidence of such infection in patients from the United Kingdom. The use of the polymerase chain reaction combined with two separate second generation anti-HCV assays is reported here in 58 UK patients with well-documented autoimmune chronic active hepatitis. All patients were in corticosteroid induced remission. All sera were collected prospectively for the specific purpose of this study. HCV-RNA was not detected by use of the polymerase chain reaction in any of the patients and antibodies to HCV were only detected in one patient. No evidence was found for the involvement of the hepatitis C virus in UK patients with classical, corticosteroid sensitive autoimmune chronic active hepatitis.

Adult↗
PubMed1993

A pattern of 5-1-1 and c100-3 only on hepatitis C virus (HCV) recombinant immunoblot assay does not reflect HCV infection in blood donors.

Current criteria for a reactive (positive) interpretation on hepatitis C virus (HCV) recombinant immunoblot assay (RIBA) require > or = 1+ reactivity to at least two of the four HCV antigens present in the assay. Given that 5-1-1 is a subcomponent of c100-3, there is concern that donor samples reacting only with these two antigens (and not with c22-3 or c33c) could be incorrectly classified as positive on the basis of limited reactivity to only one HCV gene product. It is determined that 0.23 to 0.44 percent of HCV enzyme immunoassay-repeatably reactive donor sera demonstrate a pattern of 5-1-1 and c100-3 only on RIBA. Evaluation of six such donor sera using peptide enzyme immunoassays spanning the c100-3 antigen showed highly restricted reactivity to the 5-1-1 N-terminal region of c100-3, in contrast to broad 5-1-1 and c100-3 C-terminal peptide reactivity observed in the majority of donor sera with other positive RIBA patterns. HCV polymerase chain reaction and follow-up serologic evaluations of four of these donors indicated the absence of viremia or evolving seroconversion in all cases. It is concluded that, in the blood donor setting, a pattern of only 5-1-1 and c100-3 reactivity is typically not indicative of HCV infection. To avoid overinterpretation, it is recommended that RIBA grading criteria be revised to require reactivity to two or more HCV-encoded gene products.

Amino Acid Sequence↗
PubMed1993

The effects of heparin and dietary fish oil on embolic events and the microcirculation downstream from a small-artery repair.

In recent studies we demonstrated that platelet emboli induced by arterial injury impair the microcirculation. The present study was performed to determine if heparin or dietary cod liver oil reduces the incidence of emboli following the same arterial injury and, in turn, whether these agents prevent the associated decrease in microcirculatory blood flow. The cremaster muscle of 29 male Sprague-Dawley rats was isolated on a single neurovascular bundle consisting of the iliac artery and vein and the genitofemoral nerve. Emboli were generated by a thrombogenic injury of the iliac artery, and their number and their subsequent effect on capillary perfusion in the downstream microcirculation were measured. Nine animals received heparin (10-unit IV bolus plus 10 units/hour IV infusion), 10 were fed cod liver oil (10 percent by weight of food) for 3 weeks prior to the experiment, and 9 animals receiving no treatment served as controls. The number of emboli was significantly reduced in the heparin group, but there was no accompanying improvement in capillary perfusion. In contrast, in the cod liver oil group, the number of emboli was not reduced, but there was significant improvement in capillary perfusion. These findings suggest that the harmful effect that platelet emboli have on the microcirculation is probably biochemical in nature (vasoconstriction) rather than related to simple mechanical obstruction to flow.

Anastomosis, Surgical↗
PubMed1993

The effect of prophylactic nitroglycerin infusion on the incidence of regional wall-motion abnormalities and ST segment changes in patients undergoing coronary artery bypass surgery.

The effects of nitroglycerin (NTG) on regional wall-motion abnormalities, ST segment changes, and the incidence of myocardial infarction (MI), cardiac failure, and mortality were studied in 30 patients undergoing coronary artery bypass. Patients received continuous infusions of either normal saline or NTG (1 microgram/kg per min [low dose] or 2 micrograms/kg per min [high dose]) beginning at anesthesia and continuing for 4 hours postoperatively. The occurrence of wall-motion abnormalities as detected by transesophageal echocardiography was 38 events in the normal saline group (N = 10). Significantly fewer events (p < 0.05) were recorded in the low dose and high dose NTG groups (20 events and 15 events, respectively) compared to controls. There were no significant differences between the control and NTG groups with regard to the incidence of Holter ST segment events or the incidence of MI, cardiac failure, or cardiac death. NTG reduced the incidence of echocardiographic wall-motion abnormalities in a dose dependent manner while having no significant effect on other parameters examined.

Coronary Artery Bypass↗
PubMed1993

Growth suppression of Friend virus-transformed erythroleukemia cells by p53 protein is accompanied by hemoglobin production and is sensitive to erythropoietin.

The murine allele temperature-sensitive (ts) p53Val-135 encodes a ts p53 protein that behaves as a mutant polypeptide at 37 degrees C and as a wild-type polypeptide at 32 degrees C. This ts allele was introduced into the p53 nonproducer Friend erythroleukemia cell line DP16-1. The DP16-1 cell line was derived from the spleen cells of a mouse infected with the polycythemia strain of Friend virus, and like other erythroleukemia cell lines transformed by this virus, it grows independently of erythropoietin, likely because of expression of the viral gp55 protein which binds to and activates the erythropoietin receptor. When incubated at 32 degrees C, DP16-1 cells expressing ts p53Val-135 protein, arrested in the G0/G1 phase of the cell cycle, rapidly lost viability and expressed hemoglobin, a marker of erythroid differentiation. Erythropoietin had a striking effect on p53Val-135-expressing cells at 32 degrees C by prolonging their survival and diminishing the extent of hemoglobin production. This response to erythropoietin was not accompanied by down-regulation of viral gp55 protein.

Animals↗
PubMed1993

Constitutive tyrosine phosphorylation of the T-cell receptor (TCR) zeta subunit: regulation of TCR-associated protein tyrosine kinase activity by TCR zeta.

The T-cell receptor (TCR) zeta subunit is an important component of the TCR complex, involved in signal transduction events following TCR engagement. In this study, we showed that the TCR zeta chain is constitutively tyrosine phosphorylated to similar extents in thymocytes and lymph node T cells. Approximately 35% of the tyrosine-phosphorylated TCR zeta (phospho zeta) precipitated from total cell lysates appeared to be surface associated. Furthermore, constitutive phosphorylation of TCR zeta in T cells occurred independently of antigen stimulation and did not require CD4 or CD8 coreceptor expression. In lymph node T cells that constitutively express tyrosine-phosphorylated TCR zeta, there was a direct correlation between surface TCR-associated protein tyrosine kinase (PTK) activity and expression of phospho zeta. TCR stimulation of these cells resulted in an increase in PTK activity that coprecipitated with the surface TCR complex and a corresponding increase in the levels of phospho zeta. TCR ligations also contributed to the detection of several additional phosphoproteins that coprecipitated with surface TCR complexes, including a 72-kDa tyrosine-phosphorylated protein. The presence of TCR-associated PTK activity also correlated with the binding of a 72-kDa protein, which became tyrosine phosphorylated in vitro kinase assays, to tyrosine phosphorylated TCR zeta. The cytoplasmic region of the TCR zeta chain was synthesized, tyrosine phosphorylated, and conjugated to Sepharose beads. Only tyrosine-phosphorylated, not nonphosphorylated, TCR zeta beads were capable of immunoprecipitating the 72-kDa protein from total cell lysates. This 72-kDa protein is likely the murine equivalent of human PTK ZAP-70, which has been shown to associate specifically with phospho zeta. These results suggest that TCR-associated PTK activity is regulated, at least in part, by the tyrosine phosphorylation status of TCR zeta.

Animals↗
PubMed1993

Tidal volume measurements in newborns using respiratory inductive plethysmography.

Respiratory inductive plethysmography (RIP) is a well-accepted noninvasive technology for monitoring breathing patterns in adults. Prior attempts to calibrate this device in babies have been fraught with technical difficulties, thereby limiting applications in this population. Recently, a new method, qualitative diagnostic calibration (QDC), has been shown to provide accurate calibration of tidal volume in adults. The QDC method is based upon principles of the isovolume maneuver and carried out during natural breathing without specialized respiratory maneuvers or postural changes. We calibrated RIP with QDC in the supine posture and compared tidal volume (VT) measured with RIP to VT by a face mask-pneumotachograph (PNT) in 21 healthy full-term newborns in supine and prone postures. Eleven of the babies were calibrated during active sleep and 10 in quiet sleep. The mean VT in the supine and prone postures were 19 and 25 ml, respectively. In the supine and prone postures, weighted mean difference between RIP (VT) and PNT (VT) and 95% confidence intervals were -0.05 ml (-0.27, 0.18) and -0.32 ml (-0.08, 0.55), respectively. There was no difference in the accuracy of RIP relative to PNT calibrated during active sleep when thoracoabdominal incoordination was present or quiet sleep when it was not in either the supine or the prone postures. Therefore, in full-term infants, RIP calibrated with QDC solely in the supine posture provides clinically acceptable measurements of VT in both supine and prone postures.

Analysis of Variance↗
PubMed1993

Suppression of preterm labour. Current concepts.

Preterm delivery occurs in 5 to 9% of pregnancies and the complications of prematurity account for more than 60% of perinatal mortality. In spite of tocolytic agents being available for over 20 years, and in widespread use, there has been no decrease in the number of preterm births. Many therapeutic agents have been investigated for efficacy and safety in tocolysis, including ethanol, beta 2-adrenoceptor agonists, prostaglandin synthetase inhibitors and calcium channel blockers. While the ability to delay delivery for up to 7 days has been shown, there is little convincing evidence that any further prolongation of pregnancy can be obtained. However, the value in delaying delivery until corticosteroids can be administered has been demonstrated. Problems in diagnosing preterm labour account for much of the difficulty in interpreting the literature, and the conflicting results of clinical trials.

Female↗
PubMed1993

Effect of the prenatal maternal environment on the control of breathing during non-rapid-eye-movement sleep in the developing lamb.

This study examines the effects of altering the prenatal maternal metabolic and hormonal environment via chronic cold exposure of under-fed ewes on developmental changes in breathing control of developing lambs. Breathing frequency and timing were measured during non rapid-eye-movement (non-REM) sleep in lambs born from either shorn or unshorn ewes after being maintained for at least one hour at warm (28-19 degrees C) and cool (14-5 degrees C) ambient temperatures at 1, 4, 14 and 30 days of age. Breathing frequency and oxygen consumption were significantly higher in 1 day old lambs born from shorn ewes compared with those lambs born from unshorn ewes, at both warm and cool ambient temperatures. In the shorn group breathing frequency decreased between 1 and 4 days of age and continued decreasing upto 30 days of age, during which period inspiratory and to a greater extent expiratory time, lengthened. Laryngeal "braking" of expiratory airflow was observed in more than 50% of lambs born from shorn ewes during non-REM sleep in the warm at 4, 14 and 30 days of age, and in the cold at 14 and 30 days of age. In contrast, lambs born from unshorn ewes showed no change in breathing frequency between 1 and 4 days of age, but a decrease was observed between 4 and 14 days of age, whilst laryngeal "braking" of expiratory airflow was rarely observed at any age.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

The role of transvaginal sonography in the early detection of congenital heart disease.

The antenatal diagnosis of congenital heart disease by fetal echocardiography is rarely achieved before 18-20 weeks' gestation. Transvaginal sonography allows examination of fetal anatomy at earlier gestations than the transabdominal approach. In a screening study of 270 low-risk women between 8 and 14 weeks' gestation using a 5 MHz vaginal transducer, it was possible to obtain adequate four-chamber views in over 70% from 12 weeks. In a second study of 32 women at high risk of congenital heart disease scanned between 14 and 15 weeks' gestation, satisfactory views were obtained transvaginally in 21 women. Seven of the remainder had normal cardiac anatomy confirmed by transabdominal scanning. In three of the four where normal cardiac anatomy could not be demonstrated by either transvaginal or transabdominal scanning, severe congenital heart disease was diagnosed and later confirmed. It is unlikely that transvaginal sonography will replace abdominal scanning for the screening of low-risk pregnancies, but it is a valuable addition to the early examination of those women identified as being at high risk of congenital heart disease.

Journal Article↗
PubMed1992

Mutational analysis of CD45. A leukocyte-specific protein tyrosine phosphatase.

The cytoplasmic domain of murine CD45 has been expressed using an in vitro transcription/translation system. The recombinant protein was isolated by immunoprecipitation with a specific rabbit antiserum and was shown to have protein tyrosine phosphatase (PTPase) activity. Oligonucleotide-directed mutagenesis was then used to investigate the structural requirements for PTPase activity. Although the cysteine crucial for PTPase activity resides in domain I, this domain was not active alone. Both PTPase domains of CD45 and the membrane proximal region of 77 amino acids were required for enzymatic activity. Deletion of 78 residues at the carboxyl terminus of the cytoplasmic region did not influence activity, but an additional deletion of 13 amino acids from PTPase domain II totally abolished activity. Excision of the 21-residue acidic insert in the second PTPase domain resulted in a decrease of activity of approximately 4-fold. Nine conserved residues around the critical cysteine in the first domain were found to be important for activity. Of the 3 conserved tyrosine residues in domain I, only Tyr729 was specifically required for activity.

Amino Acid Sequence↗
PubMed1992

Monosomy 7 myeloproliferative disease in children with neurofibromatosis, type 1: epidemiology and molecular analysis.

Loss of constitutional heterozygosity is a common molecular feature of cancers in which inactivation of one or more tumor suppressor genes is thought to contribute to tumorigenesis. Recent evidence suggests that the gene responsible for neurofibromatosis, type 1 (NF-1), belongs to this class of heritable cancer genes. Children with NF-1 show an increased incidence of myeloid leukemia, including juvenile chronic myelogenous leukemia (JCML) and, perhaps, the myeloproliferative syndrome (MPS) associated with bone marrow monosomy 7 (Mo 7). We have investigated five children with Mo 7: three with NF-1 and two others with suggestive evidence of NF-1. Southern blotting experiments performed in four patients showed no loss of heterozygosity in bone marrow specimens using probes linked to the NF-1 locus on the long arm of chromosome 17. Both of our patients with familial NF-1 inherited the disease from their mothers, as did 14 of 19 other cases of myeloid leukemia in children with familial NF-1. Seventeen of these 21 children were boys. Myeloid leukemia developed in 12 boys and four girls who inherited NF-1 from their mothers, and in five boys who inherited the disease from their fathers. Father-to-daughter transmission was not observed. Taken together, the presence of chromosome 7 deletions in the leukemias of children with NF-1, a pattern of inheritance favoring maternal transmission of NF-1, and the marked predilection for boys to develop JCML and Mo 7 suggest a multistep mechanism of oncogenesis in which epigenetic factors might play a role. Further investigation is required to determine if the NF-1 genes in the leukemic bone marrows of these patients have acquired point mutations or small deletions.

Blotting, Southern↗