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P Johnson

Publications and source records attributed to P Johnson.

At least 361 records · Page 20Linked to original sources
PubMed1990

DNA-directed alkylating agents. 2. Synthesis and biological activity of platinum complexes linked to 9-anilinoacridine.

Two different classes of cis-diaminedichloroplatinum(II) complexes linked to the DNA-intercalating chromophore 9-anilinoacridine have been synthesized and evaluated as DNA-targeted antitumor agents. Two different Pt chelating ligands were investigated (based on 1,2-ethanediamine and 1,3-propanediamine), designed to deliver the Pt in an orientation likely to respectively enhance either intrastrand or interstrand cross-linking. Although both sets of ligands were somewhat unstable under neutral or basic conditions with respect to disproportionation, the corresponding Pt complexes, once prepared, appeared to be quite stable. All the Pt complexes were monitored for purity by TLC, HPLC, and FAB mass spectra, and the mode of Pt coordination was established by 195Pt NMR spectroscopy. The complexes appeared to cause simultaneous platination and intercalative unwinding of plasmid DNA. In vitro studies were carried out with both wild-type and cisplatin-resistant P388 cell lines. Whereas cisplatin itself and the ethylenediamine and 1,3-propanediamine complexes used as standards were about 10-fold less active against the resistant line, the ethylenediamine-linked Pt complexes showed no differential toxicity between the two lines and the propanediamine-linked complexes showed significant differentials (up to 8-fold) in favor of the cisplatin-resistant line. However, these were no greater than those shown by the unplatinated ligands themselves. The majority of the acridine complexes were inactive in vivo against the wild-type P388 leukemia. They were very insoluble, and although a suitable formulation was found, this may have been a factor. It is also possible that these compounds bind in such a way as to direct the Pt away from the major groove.

Alkylating Agents↗
PubMed1990

Actions of bufalin and cinobufotalin, two bufadienolides respectively more active and less active than ouabain, on ouabain binding and 86Rb uptake by human erythrocytes.

1. We have reported that the bufadienolide, bufalin (purified from toad skin), was more potent than ouabain in inhibiting the sodium/potassium-dependent adenosine triphosphatase from canine kidney (Sigma) [Brownlee, A.A., Lee, G. & Mills, I.H.J. Physiol. (London) 1987; 390, 94P]. 2. The activities of bufalin and cinobufotalin were compared with ouabain in the [3H]ouabain binding assay and on 86Rb uptake in human erythrocytes. 3. When the percentage binding of ouabain-sensitive [3H]ouabain was plotted against the log of the concentration of drug in mol/l, it was shown that the bufalin curve was shifted to the left of that of ouabain and that of cinobufotalin was to the right. 4. Linear regression lines were fitted to the data transformed as the log of (p/1--p) plotted against the log of the drug concentration, where p is the proportion of maximal ouabain-sensitive activity at the drug concentration being considered. The IC50 (the concentration of drug producing a 50% change in the maximal ouabain-sensitive response) was 1.4 x 10(-9) mol/l for bufalin, 9.7 x 10(-9) mol/l for ouabain and 1.70 x 10(-7) mol/l for cinobufotalin. 5. The introduction of bufalin 1 h before ouabain reduced the binding of [3H]ouabain to 23.4 +/- 1.5% (P less than 0.001). Bufalin added in the second hour reduced the ouabain-sensitive binding from 100 +/- 1.9% to 87.4 +/- 2.9% (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Birth asphyxia and the intrapartum cardiotocograph.

The intrapartum cardiotocographs (CTGs) of 38 severely asphyxiated, term infants, born during a 17-month period, and those of 120 healthy term infants acting as controls were independently reviewed by three investigators who were unaware of the clinical outcome. Inter-observer agreement was good (Kappa statistic = 0.74, P less than 0.0001). The investigators found that cardiotocographic abnormalities were present in 33 of the asphyxiated infants (87%) and in 35 of the controls (29%) and predicted that the abnormalities were severe enough to lead to significant fetal metabolic acidosis at delivery in 23 asphyxiated infants (61%) and in 11 controls (9%). The differences between the two groups were highly significant (P less than 0.001). Using the traditional diagnostic criteria for fetal distress, the investigators found that fetal blood sampling was indicated in 58% of cases in the asphyxia group and in 20% of controls but was only performed in 16% of asphyxiated infants and in 8% of controls. Furthermore, the median response times of delivery suite staff for abnormal fetal heart rate patterns were similar whether the FHR changes, classified using Krebs' CTG scoring system, were moderate or severe: 80 min and 90 min, respectively. These findings suggest that interpretation of the intrapartum CTG continues to pose major problems for practising obstetricians.

Acidosis, Respiratory↗
PubMed1990

Distribution of substance P receptors in rabbit airways, functional and autoradiographic studies.

We have studied systematically the distribution of receptors for substance P in the airway smooth muscle of the rabbit using both functional studies and light-microscopic autoradiography. Four areas of the respiratory tract were examined: the midtrachea (T1) and proximal, middle and distal portions of the right main bronchus (B1, B2 and B3, respectively). The magnitude of the contractile response to substance P in preparations from six to eight animals was location-dependent, increasing significantly from proximal to distal areas. Maximal tension expressed as a function of tissue weight +/- S.E.M. was 24.8 +/- 3 for T1, 39 +/- 10 for B1, 108 +/- 31 for B2 and 160 +/- 42 for B3. The potency of substance P in B2 and B3 was significantly greater (EC50 = 4.8 x 10(-7) M; 2.8 x 10(-7) M, respectively) than that in T1 (2.5 x 10(-6) M). After inhibition of endogenous enkephalinase by phosphoramidon there was an increase in sensitivity to substance P in both T1 (EC50 = 2.3 x 10(-7) M, n = 5) and B3 (2.6 x 10(-9) M, n = 5). There was remarkable agreement in the results obtained with autoradiography. No binding sites (0) were visualized to Bolton Hunter substance P in T1. Sparse but specific binding (+) was seen in B1, whereas it was marked ( ) in B2 and very dense ( ++) in B3. Thus, our results have shown that receptors for substance P are more numerous in the distal than proximal airways of the rabbit. This may indicate a physiological role for substance P in the regulation of airway smooth muscle tone in the distal airways.

Animals↗
PubMed1990

Early recognition of critical stenosis high in the left anterior descending coronary artery.

We describe an electrocardiographic finding indicative of critical stenosis high in the left anterior descending coronary artery. Patients at risk have prior angina and normal or minimally elevated cardiac enzyme levels. Their electrocardiogram exhibits no precordial Q waves and little or no ST elevation but, rather, deep and symmetric T waves. The presence of these findings indicates that the patient has had subendocardial ischemia or infarct, which, if not treated, may evolve to encompass the entire thickness of the myocardium. The need for prompt recognition of these critical warning signs is obvious. Critical care nurses must be prepared to recognize and act on these findings in a rapid, efficient manner.

Coronary Disease↗
PubMed1989

Identification of the alternatively spliced exons of murine CD45 (T200) required for reactivity with B220 and other T200-restricted antibodies.

Cell lines expressing specific variants of murine CD45 (T200) were established by infection with retroviral constructs of four cDNAs encoding different forms of CD45. These lines were then used to determine which sequences encoded by alternatively spliced exons of CD45 were required to generate antigenic determinants recognized by anti-CD45 mAbs. The binding of two B220 antibodies (14.8 and RA32C2) to CD45 was dependent on the expression of the first alternatively spliced exon (exon A). A third B220 antibody, RA3-6B2, did not bind to any of the forms of CD45 expressed on fibroblasts. A newly defined anti-CD45R antibody, C363.16A, reacts with an antigenic site dependent upon the expression of the second alternatively spliced exon, exon B.

Animals↗
PubMed1989

Acid-base status at birth and neurodevelopmental outcome at four and one-half years.

Two hundred thirty term infants with measured acid-base status in umbilical arterial blood at birth were selected from 1210 consecutive deliveries for detailed neurodevelopmental follow-up at age 4 1/2 years; 203 were examined. Cutoff points approximately 1 SD from the mean (pH less than or equal to 7.10; base deficit greater than 12 mmol/L) were used to define acidosis. No statistically significant associations between acidosis and developmental outcome were found. The highest proportion of unimpaired children was found among those who were most severely acidotic at birth (pH less than or equal to 7.04; 2 SD below mean), but this finding was not statistically significant. These findings suggest that the ability of the fetus to produce an acidosis in response to the stress of labor may be beneficial to long-term outcome. The 10 nonacidotic babies with 1-minute Apgar scores of less than or equal to 3 showed statistically significant deficits in some areas. Coincident acidosis was not associated with a worse outcome for infants with low Apgar scores.

Acid-Base Equilibrium↗
PubMed1989

Desmin-containing intermediate filaments: structural analysis using monoclonal antibodies.

1. Monoclonal antibodies have been raised against N- and C-terminal desmin sequence regions. 2. The antibodies decorated desmin intermediate filaments in a helical fashion with four antibody molecules per helix turn. 3. The filaments could be decorated with both types of antibody consecutively. 4. These results support a model of intermediate filament assembly in which the tetrameric protofilaments are aligned in a staggered fashion with partial overlapping of the central rod domain regions of the desmin sequence.

Animals↗
PubMed1989

Effects of L-1-methyl-histidine and the muscle dipeptides carnosine and anserine on the activities of muscle calpains.

1. Carnosine, anserine and L-1-methyl-histidine activated muscle calpain II assayed at 2.5 mM Ca2+. 2. At 5 microM Ca2+, none of these compounds activated calpain II sufficiently to bring its activity up to the level measured at 2.5 mM Ca2+. 3. Carnosine increased, whereas both anserine and L-1-methyl-histidine decreased the inhibitory effect of calpastatin on calpain II. 4. These results suggest that although the compounds are not potent activators of calpain II, the ratio of the dipeptides in muscle may have an effect on calpain II-calpastatin interaction.

Alanine↗
PubMed1989

Changes in CD45 isoform expression accompany antigen-induced murine T-cell activation.

Leukocytes express a family of plasma membrane proteins called CD45 or the leukocyte common antigen. Isoforms of various molecular masses, 180-240 kDa, are produced by alternative splicing and usage of three exons, named A, B, and C, that encode the N-terminal portion of the external domain. By using monoclonal antibodies that precipitate B exon-dependent and B exon-independent isoforms we find that both murine CD4+ and murine CD8+ T cells selectively down-regulate the B exon-dependent forms of CD45 during an immune response. This change was monitored by using fluorescence-activated cell sorter (FACS) analysis and immunoprecipitation from surface radioiodinated and metabolically labeled cells. The loss of the 190-kDa B exon-dependent isoform during T-cell activation is accompanied by an increased production of a 180-kDa form, which does not contain the B exon-encoded sequence. This accounts for our observation that the overall expression of CD45, as assessed by FACS analysis, does not change.

Animals↗
PubMed1989

Expression of CD45 alters phosphorylation of the lck-encoded tyrosine protein kinase in murine lymphoma T-cell lines.

CD45 is a family of high molecular weight leukocyte cell surface glycoproteins. Recently, two related subregions of the cytoplasmic domain of CD45 have been shown to have 30-40% amino acid identity with a human placental protein phosphotyrosine phosphatase, and CD45 isolated from human spleen was found to exhibit intrinsic protein phosphotyrosine phosphatase (EC 3.1.3.48) activity. In the present studies, we demonstrate that each of the known isoforms of murine CD45 has an equivalent basal level of protein phosphotyrosine phosphatase activity and establish that this enzymatic activity is associated with the cytoplasmic domain of the glycoprotein. Studies with three independent sets of well-characterized parental CD45+, mutant CD45-, and revertant CD45+ lymphoma cell lines indicate that loss of CD45 increases the phosphorylation of the src-related leukocyte-specific tyrosine protein kinase p56lck on tyrosine-505, a putative negative regulatory site. This suggests that CD45 may play a role in leukocyte growth regulation by altering the kinase activity of p56lck.

Animals↗
PubMed1989

Immediate breast reconstruction: reducing the risks.

One-hundred and sixty-five consecutive immediate breast reconstructions in 157 patients were reviewed. Reconstructions were performed with tissue expanders (53 percent) or immediate gel prostheses (47 percent). Immediate reconstruction was associated with an 18 percent rate of implant loss. Certain risk factors were identified at the p less than 0.05 level using immediate gel implants: failure to achieve complete muscle coverage of the implant, smoking at the time of surgery, initial gel implants of 400 ml or more volume, and age. Expander loss was increased by detaching the pectoralis major (p less than 0.05) and probably by lack of complete muscle coverage in general. Chemotherapy, history of previous smoking, and clinical stage of the carcinoma did not seem to affect reconstructive success. Smoking and patient age should be considered during patient selection for immediate reconstruction. Muscle coverage of the prosthesis should always be attempted. Muscle coverage is mandatory in the smoker. Gel implants of 400 ml or more volume are to be avoided at the initial operation. This approach should enable all surgeons to achieve lower rates of implant loss.

Adult↗
PubMed1989

Mortalities associated with use of a commercial suspension of polyvinyl alcohol.

Two cases of symptomatic neonatal hepatic arteriovenous malformation (AVM) are presented. Both were treated with percutaneous transcatheter embolization and a commercially available polyvinyl alcohol suspension. Both infants died soon after AVM embolization. The results of laboratory examination of particle-size homogeneity of this commercial suspension demonstrate marked inhomogeneity of particle size very probably contributed to the death of these patients. A protocol has been developed to help determine appropriate particle size in individual cases; this may help prevent such catastrophic results during transcatheter embolization.

Arteriovenous Malformations↗
PubMed1989

The endocrine and metabolic response to feeding in the developing lamb.

Oxygen consumption (VO2), carbon dioxide production (VCO2), heart rate and the arterial plasma concentrations of glucose, non-esterified fatty acids, thyroxine (T4), 3,5,3'-tri-iodothyronine (T3), TSH, insulin, cortisol and GH were measured before and after feeding a formula milk diet to lambs aged 9, 21, 33 and 46 days. In all age groups, VO2, VCO2 and heart rate increased significantly following feeding and this effect was greatest at 9 days of age. Both VO2 and VCO2 before and after feeding decreased with age. Plasma concentrations of T3 before feeding did not change with age, but plasma T3 levels after feeding were significantly higher in lambs aged 9 days compared with 33 and 46 days. There was no effect of feeding on TSH or age on plasma TSH and T4 concentrations. In all age groups, glucose concentration increased after feeding and was paralleled by a rise in insulin concentration. At 9 and 21 days of age plasma glucose and insulin concentrations reached a plateau after the initial postprandial increase and together with a rise in respiratory quotient was indicative of a stimulation of carbohydrate oxidation. Plasma concentrations of GH increased after feeding at 21 days and older, when the mean growth rate was also stimulated by 75%. Basal metabolic rate and dietary-induced thermogenesis both decreased with age and, as a result, metabolism associated with an increase in GH levels after feeding became more efficient in terms of growth rate after 21 days. It is therefore concluded that there are major endocrine and cardiorespiratory changes in response to feeding of the young lamb which are important in stimulating and/or facilitating its growth and development.

Animal Nutritional Physiological Phenomena↗
PubMed1989

The control of thermoregulation in the developing lamb during slow wave sleep.

This study investigates the mechanisms involved in adjusting metabolic rate in response to acute changes in ambient temperature close to thermoneutrality during postnatal development. Twelve lambs were prepared for sequential studies at 4, 14, 30, 45 and 55 days of age. During each study they were maintained at ambient temperatures of 5, 10, 15, 20, 25 and 30 degrees C for at least 1 h and until a slow wave sleep epoch was established. Eight lambs completed all studies. In these there was a significant fall in oxygen consumption with age which was independent of ambient temperature. This effect was closely related to a decrease in plasma triiodothyronine concentration that was greatest between 4- and 14-days old lambs and was not associated with a change in the plasma concentration of thyrotrophin or thyroxine. In 4-days old lambs oxygen consumption was increased at ambient temperatures of 5 and 10 degrees C by non-shivering thermogenesis, whilst in 14- and 30-days old lambs this effect was achieved by shivering. On the basis of significant changes in oxygen consumption and/or the occurrence of shivering (lower critical temperature) and panting (upper critical temperature) we have shown that there is a fall in both upper and lower critical temperature with age and a widening of the thermoneutral zone. This was associated with a decrease in the plasma cortisol concentration and heart rate as measured at thermoneutrality, whilst rectal temperature increased from 4 to 30 days of age. The other 4 lambs, 3 of which died between 7 and 17 days of age, had low plasma triiodothyronine concentrations when studied at 4 and/or 14 days of age and their oxygen consumption at thermoneutrality was significantly lower than the normal group at 14 days. Shivering thermogenesis occurred at an earlier age and control of body temperature was less effective. It is concluded that triiodothyronine has an important role in the control of metabolic rate in the developing lamb even to meet modest changes in ambient temperature, and possibly directly in survival.

Animals↗