Search PubMed⌕ Search

Biomedical subjects

R Johnson

Publications and source records attributed to R Johnson.

At least 379 records · Page 21Linked to original sources
PubMed1990

Simultaneous occurrence of calcium pyrophosphate dihydrate and basic calcium phosphate (hydroxyapatite) crystals in a knee.

An 82-year-old man developed periarticular roentgenographic calcifications of the knee joint. Fragments of meniscus and peritendinous tissue were collected during total knee arthroplasty. Crystals were released from tissues by collagenase digestion. Calcium pyrophosphate dihydrate crystals were identified in the meniscus, and basic calcium phosphate crystals were identified in the peritendinous tissue. Methods of crystal identification included compensated polarized light microscopy, scanning electron microscopy with X-ray energy dispersive analysis, and X-ray diffraction.

Aged↗
PubMed1989

Mechanism of transport and intracellular binding of porfiromycin in HCT 116 human colon carcinoma cells.

The mechanism of uptake and efflux of porfiromycin (PFM) by HCT 116 human colon carcinoma cells or freshly obtained human RBC was investigated. The time course of uptake of radioactivity upon exposure of HCT 116 cells to [14C]PFM showed one fast and one slow phase of linear increase. The initial phase of PFM uptake was not saturable with external drug concentrations from 2 to 100 microM. PFM accumulation was temperature dependent with a temperature coefficient (Q10 24-37 degrees C) of 2.3 +/- 0.3. PFM uptake was not affected either by individual inhibitors such as 1 mM 2,4-dinitrophenol, sodium azide, iodoacetic acid, ouabain, 0.02 mM oligomycin, p-hydroxylmercuribenzoate, 0.2 mM N-ethylmaleimide, or by combinations of inhibitors. PFM uptake did not demonstrate competitive inhibition by unlabeled PFM and mitomycin C. Efflux of cellular radioactivity was not affected by the above mentioned inhibitors or by verapamil, diltiazem, or trifluoperazine. Only aliphatic alcohols accelerated the initial influx rate. The RBC, however, only exhibited the initial fast accumulation of [14C]PFM, and all the 14C accumulated by RBC was exchangeable. These data demonstrate that the uptake and the efflux of PFM in HCT 116 cells and RBC comprise a passive diffusion process.

Animals↗
PubMed1989

Does autonomic neuropathy in diabetes cause hearing deficits?

This study examined the effect of autonomic neuropathy on hearing in diabetes mellitus. Twelve diabetics with autonomic neuropathy and eleven healthy controls were examined for hearing loss using standard audiological tests. Several subjects in both groups had some abnormal hearing tests, but the incidence was no greater in the diabetic group. No group trends were apparent. Diabetic autonomic neuropathy is unlikely to be associated with hearing deficits.

Acoustic Impedance Tests↗
PubMed1989

Activation of Chlamydomonas rhodopsin in vivo does not require isomerization of retinal.

The unicellular eukaryote Chlamydomonas reinhardtii is a phototactic alga that swims toward or away from light, using rhodopsin as the photopigment. The activity of retinal analogues was tested in the mutant FN68, which has high phototactic sensitivity only after incubation with retinal or analogues of retinal. Analogues prevented from isomerizing about the 7-ene, 9-ene, 11-ene, 13-ene, or 15-ene (C = N+H) bonds retained full activity. Also, bleaching, protonation of the N, and a stable geometrically altered chromophore are not required for full activity. An attractive hypothesis is that charge redistribution in the excited state of retinal directly triggers the activity of rhodopsin.

Chlamydomonas↗
PubMed1989

Effects of liver disease on the disposition of ciramadol in humans.

To determine the effects of liver disease on the disposition of ciramadol, an analgesic that undergoes ether glucuronidation, we studied its plasma pharmacokinetics in 10 patients with stable cirrhosis, 8 with acute viral hepatitis, and 16 age-matched healthy controls. Renal excretion of the glucuronides was also determined. In healthy controls given a single intravenous dose of the drug the t 1/2 was 3.4 +/- 0.3 hrs and the systemic clearance was 668 +/- 109 ml/min of which renal clearance was 320 +/- 73 ml/min and non-renal clearance 349 +/- 74 ml/min. The corresponding values after an oral dose were similar. Renal clearance was related directly to the estimated creatinine clearance. Moreover, the renal clearance of ciramadol exceeded creatinine clearance, suggesting that the drug was excreted not only by glomerular filtration but also by tubular secretion. The systemic clearance of intravenous ciramadol was diminished by 40% in cirrhosis, P less than 0.05, due to a reduction in renal clearance, while non-renal clearance remained normal. Renal clearance of the inactive glucuronides, on the other hand, was not affected. In patients with acute viral hepatitis, systemic clearance was unchanged, but renal clearance of ciramadol tended to increase during the acute phase of the disease and to return toward normal after recovery. Renal excretion of the inactive glucuronides was decreased by 48% (P less than .05). These findings suggest that the non-renal ether glucuronidation of ciramadol remains intact in patients with stable cirrhosis or acute viral hepatitis. However, the renal clearance of the drug may be impaired in cirrhosis, but tends to be enhanced in acute hepatitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Employment after severe head injury: do the Manpower Services Commission schemes help?

This paper describes the use of Manpower Services Commission (MSC) employment rehabilitation schemes by a series of severely head injured people. Most of those who achieved employment did so without making use of MSC schemes. A majority of those using MSC schemes remained unemployed at last follow-up. Those attending MSC schemes were more likely to have been in education at the time of injury. Some of those previously in work used schemes, but only after they had already failed at work or had had a long period out of work. MSC schemes may fail to meet the needs of the head-injured because many are too short or use is made of them at too long an interval after the injury. They do not cater well for special training and the flexible approach that is necessary for successful employment rehabilitation of those suffering from brain injury. The priority is for training schemes that can be carried out within the workplace and for support and incentives to employers to help head-injured people return to their previous work.

Adult↗
PubMed1989

Synthesis, tubulin binding, antineoplastic evaluation, and structure-activity relationship of oncodazole analogues.

In an attempt to identify a soluble oncodazole analogue that could be easily formulated, a series of substituted oncodazoles was synthesized and evaluated for tubulin binding affinity, in vitro cytotoxicity against cultured mouse B-16 cells, and ability to prolong lifespan at the maximally tolerated dose in the P388 mouse leukemia model. Biological evaluation of all the isomeric methyloncodazoles demonstrated the thiophene 4'-position to be the only site of significant bulk tolerance, although substitution of this position with polar or charged functional groups abolished biological activity. Simple esters of the 4'-carboxymethyloncodazole were shown to have enhanced antitumor activity and tubulin binding affinity relative to oncodazole. Despite a failure of this study to identify a water-soluble oncodazole with antitumor activity, the structure-activity relationship developed led to a derivative with enhanced activity in the P388 leukemia model and facilitated the preparation of a biologically active photolabile analogue.

Animals↗
PubMed1989

3-Quaternary ammonium 1-carba-1-dethiacephems.

A series of structurally unique 1-carba-1-dethiacephems is described. The structural stability of the 1-carba-1-dethiacephem nucleus was essential for the preparation of this series of 3-quaternary ammonium carbacephems. The known p-nitrobenzyl 7 beta-(phenoxyacetamido)- 3-[(trifluoromethyl)sulfonyl]oxy]-1-carba-1-dethia-3-cephem- 4-carboxylate served as both a quaternization substrate as well as a precursor to derivatives such as allyl 7 beta-[[2-[allyloxy)carbonyl]amino-4- thiazoly] (methoxyimino)acetyl]amino]-3-[(trifluoromethyl) sulfonyl] oxy]-1-carba-1-dethia-3-cephem-4-carboxylate. Quaternization of these enol triflates was accomplished either by dissolution in acetonitrile containing the base or by dissolution in the base, with or without warning to 50 degrees C. Bases nucleophilic enough to displace the triflate include a variety of substituted pyridines and N-methylimidazole. Deprotection then produced a very active series of 1-[7 beta-[(2-amino- 4-thiazolyl)(methoxyimino)acetyl]amino]-2-carboxy-8-oxo- 1-azabicyclo[4.2.0]oct-2-en-3-yl] quaternary ammonium hydroxide inner salts. These compounds were extremely potent antibacterials against a broad range of Gram-positive and -negative bacteria including constitutive cephalosporinase producers, such as Enterobacter cloacae. The compounds exhibit similar hydrolysis kinetics and pharmacokinetics to the analogous cephalosporin-3'-quaternary ammonium salts.

Animals↗
PubMed1989

Role of platelets in smooth muscle cell proliferation and migration after vascular injury in rat carotid artery.

Intimal lesion formation was investigated in rats made thrombocytopenic by a single i.p. injection of a polyclonal antibody made against rat platelets that reduced circulating platelet counts to less than 1% of normal. The carotid artery was then denuded of endothelium with a 2 French balloon catheter, after which no platelets were found adhering to the exposed subendothelium. In control animals, platelets adhered instantly to the denuded artery. Six hours after denudation mRNA for ornithine decarboxylase, a marker for early G1 events, was found to be elevated in both thrombocytopenic and control arteries. Two days after injury the smooth muscle cell replication rate in thrombocytopenic rats was found to be significantly elevated as compared with that in uninjured carotids (13.7% +/- 8.4% vs. 0.65% +/- 0.23%) but was similar to the replication rate observed in denuded carotid arteries from animals treated with nonimmune IgG. One important difference between these animals was that no intimal thickening was observed in thrombocytopenic animals at day 4, and by day 7 the intimas were still significantly smaller than those from control rats. In a separate group of animals which were thrombocytopenic for the entire experiment, no intimal lesions were observed 7 days after injury by balloon catheter. From these results, we conclude that platelets do not play a role in the initiation of smooth muscle cell proliferation after injury by balloon catheter but may regulate their movement into the intima.

Animals↗
PubMed1989

Expression of proteinase inhibitors I and II in transgenic tobacco plants: effects on natural defense against Manduca sexta larvae.

Genes containing the cauliflower mosaic virus 35S promoter fused to open reading frames coding for tomato proteinase inhibitor I, tomato inhibitor II, and potato inhibitor II were expressed in transgenic tobacco plants. Inhibitor I and II proteins were identified by immunoblotting and quantified by immunoradial diffusion. Both inhibitors exhibited the molecular weights found for the native proteins in their natural environments. Extracts of leaves from transformed plants contained inhibitory activities against trypsin and chymotrypsin that reflected the levels of inhibitor I or II protein present. The results demonstrate that in tobacco leaves the introns of both inhibitor I and inhibitor II genes were excised correctly and that pre and prepro inhibitor I and II proteins were correctly processed. Growth of Manduca sexta larvae (tobacco hornworms) feeding on leaves of transgenic plants containing inhibitor II, a powerful inhibitor of both trypsin and chymotrypsin, was significantly retarded, compared to growth of larvae fed untransformed leaves. Levels of inhibitor II protein as low as 50 micrograms/g of tissue moderately affected larval growth, whereas levels above 100 micrograms/g severely reduced growth. The presence of tomato inhibitor I protein, a potent inhibitor of chymotrypsin but a weak inhibitor of trypsin, in transgenic tobacco leaves had little effect on the growth of the larvae. These experiments indicated that trypsin inhibitory activity, but not chymotrypsin inhibitory activity, was mainly responsible for the inhibition of larval growth.

Animals↗
PubMed1989

Alfentanil and propofol infusions for surgery in the burned patient.

We have studied combinations of alfentanil and propofol for total i.v. anaesthesia in 24 severely burned patients. No inhalation agents were used. After a loading dose of alfentanil 100 micrograms kg-1, the intraoperative requirement was 1.24 (SEM 0.7) micrograms kg-1 min-1, and after a propofol induction dose of 2 mg kg-1 the maintenance rate was 100 micrograms kg-1 min-1. Initial hypotension occurred after induction of anaesthesia, but during the operation, cardiovascular variables were stable. After adequate antagonism of neuromuscular block, respiratory depression persisted in three patients when the two agents were discontinued simultaneously; this was not seen when alfentanil was discontinued 15 min before propofol. Quality of recovery was good, and satisfactory postoperative analgesia was present in the majority of patients 2 h after operation. This study indicates that total i.v. anaesthesia with a combination of alfentanil and propofol appears to be satisfactory in burned patients.

Adolescent↗
PubMed1989

Lamellar body formation precedes pulmonary surfactant apoprotein expression during embryonic mouse lung development in vivo and in vitro.

The purpose of this investigation was to determine whether lamellar inclusion body (LB) formation and surfactant apoprotein (SP-35) production are directly coordinated by temporal and positional information during development. In the present study we report a comparison between embryonic B10.A mouse lung morphogenesis and cytodifferentiation in vivo with that observed during organ culture in serumless medium. Precursor LB were first detected at embryonic day 12 (E12d), and progressively larger numbers and forms were produced during subsequent differentiation of respiratory alveolar duct epithelium. SP-35 was first detected during the canalicular period (E16.5d). Lung cultures (E12d) showed pseudoglandular and canalicular periods of morphogenesis, and both ciliated epithelial and type II cell differentiation. Nonciliated cells produced increasing numbers of lamellar inclusion bodies throughout the culture period. SP-35 was detected at 9 days in vitro (d.i.v.). These observations indicate (i) precursor LB formation precedes SP-35 expression and is not dependent on apoprotein synthesis; (ii) E12d lung development in vitro using serumless medium proceeds at a rate equivalent to 0.5 days in vivo through 11 d.i.v.; and (iii) morphogenesis and differentiation occur in the absence of exogenous hormones and growth factors. The cell-cell interactions that play a role in morphogenesis and cell differentiation appear to be intrinsic to the developmental program for embryonic lung development and are likely to be mediated by autocrine and/or paracrine factors.

Apoproteins↗
PubMed1989

Auditory and visual P300s in temporal lobectomy patients: evidence for modality-dependent generators.

The P300 component of the event-related brain potential (ERP) was studied in epileptic patients with unilateral resections of medial temporal lobe areas of the brain. The patients and controls were tested in an oddball paradigm in two conditions: counting and reaction time. Both auditory and visual stimuli were used to elicit ERP activity in different blocks. Despite the reported presence of locally-generated auditory and visual P300-like potentials in these areas, no evidence was found of any surgically-related hemispheric asymmetries in the scalp distribution of the P300 or Slow Wave for stimuli in either modality. Moreover, compared to normal controls, there were no significant reductions in overall P300 amplitude in the patients. The patients did show a double dissociation in their frontal ERP activity: the left temporal lobectomy patients showed apparent decreased frontal auditory P300 amplitudes but normal visual P300 amplitudes, whereas the right temporal lobectomy patients showed the opposite pattern. These results appeared to be due to the presence of a long-duration slow wave rather than to alterations in P300 amplitude. These data do not support the presence of a significant contribution by a hippocampal/amygdala generator to the activity of the scalp-recorded P300 in the oddball paradigm. Topographic comparisons on normalized amplitudes revealed significantly different scalp distributions as a function of stimulus modality, event probability, and task for both the P300 and Slow Wave components. These data indicate that the amplitude variations associated with each experimental variable are due to the activity of a separate underlying neural source. The sources of task and probability effects on P300 and Slow Wave amplitude each appeared to be modality-independent generators. The nature of the third, modality-related generator is less clear. These results uphold the tenets of the model of P300 amplitude proposed by Johnson (1986) and argue against the idea that the P300 is a unitary phenomenon.

Adult↗