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Biomedical subjects

D W Johnson

Publications and source records attributed to D W Johnson.

At least 109 records · Page 6Linked to original sources
PubMed1996

Xenon/computed tomography cerebral blood flow and its use in clinical management.

The main advantages of stable Xe/CT is that it noninvasively provides rapid access to high-resolution, quantitative, local CBF information coupled to CT anatomy. The information obtained is valid even in disease states because a partition coefficient is directly calculated for each voxel as small as 1 x 1 x 5 mm3. CBF studies can be repeated within 20 minutes, allowing the assessment of hemodynamic states. The technology can be incorporated into all existing CT technology at relatively little expense. The disadvantages are the radiation dose from the CT scanner, the pharmacologic effects of xenon gas, and the limitations of survey. The radiation dose is significant but it is focused to the least radiation-sensitive region of the body (scalp, skull, and brain) so that the effective cancer causation risk is lower than any other CBF study that delivers isotope indescriminatly to the body. The pharmacologic properties of xenon are associated with several potential problems. Xenon alters the sensorium of many individuals and may cause patient motion. This can be minimized with careful prestudy positioning and reassurance of the patient during the study. Most patients find the sensation enjoyable; however, occasionally, a patient cannot tolerate the perception of "losing control" and the study has to be stopped. One of the concerns regarding Xe/CT is that at the 80% level, xenon has anesthetic properties. At less than 33% xenon (with the difference being oxygen), the side effects have, in fact, been few and transient, with a mild hyperesthetic and disassociated feeling being the rule. Although xenon-induced apnea was reported as a consequence of xenon inhalation, the report involved the inhalation of 100% xenon, and at the levels recommended for imaging, holding one's breath for more than 20 seconds is rare. The other concern is the degree of flow activation that occurs with xenon inhalation and its effect on the accuracy of the measurements. In part, because of the "robust" nature of the Kety-Schmidt equations and because a significant xenon-induced flow activation is delayed for about 2 minutes, the effect of the flow activation is, in fact, minimal (less than 5% elevation of calculated flow values from true values). Although an earlier study by Obrist36 suggested that the error induced by flow activation was significant, a recent computer simulation study by the same author identified a maximal theoretical error of less than 5%. Previously, Xe/CT studies were limited to three brain levels, but with the new helical CT scanners, nine levels can now be studied. Most of the concerns over the technology have been resolved (Table 1). As a result, more clinicians around the world are beginning to use this technology when they need rapid access to quantitative CBF information about their patients.

Acetazolamide↗
PubMed1995

Polyenoic very-long-chain fatty acids mobilize intracellular calcium from a thapsigargin-insensitive pool in human neutrophils. The relationship between Ca2+ mobilization and superoxide production induced by long- and very-long-chain fatty acids.

Fatty acids with more than 22 carbon atoms (very-long-chain fatty acids; VLCFAs) are normal cellular components that have been implicated in the pathophysiology of a number of peroxisomal disorders. To date, however, essentially nothing is known regarding their biological activities. Ca2+ mobilization is an important intracellular signalling system for a variety of agonists and cell types. Given that several polyunsaturated long-chain fatty acids mobilize intracellular Ca2+ and that we have postulated that the VLCFAs may be involved in signal transduction, we examined whether the tetraenoic VLCFA induced Ca2+ mobilization in human neutrophils. We report that fatty acid-induced intracellular Ca2+ mobilization declined for fatty acid species of more than 20 carbon atoms, but increased again as the carbon chain length approached 30. This Ca2+ mobilization occurred independently of inositol 1,4,5-triphosphate production and protein kinase C translocation and involved both the release of Ca2+ from the intracellular stores and changes to the influx or efflux of the ion. We further observed that triacontatetraenoic acid [30:4(n-6)] mobilized Ca2+ from a thapsigargin-insensitive intracellular pool distinct from the thapsigargin-sensitive pools affected by arachidonic acid [20:4(n - 6)] or N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP). 20:4 (n - 6) induced strong superoxide production (chemiluminescence) which was inhibited by thapsigargin pretreatment. In contrast, fatty acid-induced superoxide production progressively declined as the carbon chain length increased beyond 20-22 carbon atoms. Further studies suggested that the thapsigargin-insensitive Ca2+ mobilization elicited by 30:4 (n - 6) was not related to oxyradical formation, while the thapsigargin-sensitive Ca2+ mobilization induced by 20:4 (n - 6) may be involved in the initiation but not necessarily the maintenance of superoxide production. In conclusion, this is the first report to demonstrate a biological activity for the VLCFA and indicates that 30:4 (n - 6) influences second messenger systems in intact cells that differ from those affected by long-chain fatty acids such as 20:4 (n - 6).

Calcium↗
PubMed1995

Role of subunit-9 of mitochondrial ATP synthase in Batten disease.

The role of subunit-9 of mitochondrial ATP synthase in Batten disease was defined by characterizing the expression of genes encoding this protein in human tissues. Two genetically distinct neuronal ceroid-lipofuscinoses (NCL) comprise Batten disease: the late-infantile (LINCL) and juvenile (JNCL) types. We tested cell lines and tissues from both types of patients, along with normal controls. Differences in expression between diseased and normal samples were found for both mRNA and protein. Antibody staining of subunit-9 protein was detected in LINCL and JNCL tissues, and in 6 LINCL and 4 of 5 JNCL fibroblast lines. No immunoreactivity was seen in fibroblasts from obligate carriers, normal controls, and 6 other storage disease controls, with the exception of faint staining in Niemann-Pick, type C cells. There was an appreciable difference in staining pattern in both tissue sections and fibroblasts between LINCL and JNCL. Three subunit-9 transcripts (Hum1, Hum2, and Hum3) were specifically detected in NCL and normal human tissue from heart, liver, brain, muscle, and pancreas. Transcriptional regulation of subunit-9 genes was found to be altered in Batten disease. Pseudogenes related to each of the subunit-9 genes were isolated. Sequence analysis of cDNAs spanning the protein-coding regions of the Hum1, Hum2, and Hum3 genes showed conclusively that the primary defect(s) causing NCL are not mutations in the protein-coding regions of the 3 known subunit-9 genes.

Adult↗
PubMed1995

Prior morphine exposure enhances ibogaine antagonism of morphine-induced locomotor stimulation.

Ibogaine is currently being investigated for its potential use as an anti-addictive agent. In the present study we sought to determine whether prior morphine exposure influences the ability of ibogaine to inhibit morphine-induced locomotor stimulation. Female Sprague-Dawley rats were pretreated once a day for 1-4 days with morphine (5, 10, 20 or 30 mg/kg, i.p.) or saline and then received ibogaine (40 mg/kg, i.p.) 5 h after the last morphine pretreatment dose. Compared to rats pretreated with saline, rats pretreated with morphine (10, 20 or 30 mg/kg, i.p.) before ibogaine (40 mg/kg, i.p.) showed a significant reduction in morphine-induced (5 mg/kg, i.p.) locomotor stimulation when tested 29 h after ibogaine administration. Furthermore, this effect was apparent over a range of ibogaine (5-60 mg/kg, i.p.) and morphine test (2.5-5 mg/kg, i.p.) dosages. Doses of ibogaine (5 and 10 mg/kg, i.p.) which alone were inactive inhibited morphine-induced locomotor activity when rats had been pretreated with morphine. These results, showing that morphine pre-exposure affects ibogaine activity, suggest that variable histories of opioid exposure might account for individual differences in the efficacy of ibogaine to inhibit opioid addiction.

Animals↗
PubMed1995

Recovery of gastrointestinal function after renal transplantation in a patient with sclerosing peritonitis secondary to continuous ambulatory peritoneal dialysis.

We describe the rapid and dramatic improvement in gastrointestinal function that occurred after successful renal transplantation in a women with severe sclerosing peritonitis secondary to continuous ambulatory peritoneal dialysis (CAPD). We postulate that the antiinflammatory effect of the immunosuppressive agents was the most important factor leading to the patient's recovery.

Adult↗
PubMed1995

Efficacy of frequent nebulized ipratropium bromide added to frequent high-dose albuterol therapy in severe childhood asthma.

OBJECTIVE: The objective of this trial was to determine the efficacy of frequent nebulized ipratropium added to high-dose albuterol therapy in children with severe asthma. METHODS: One hundred twenty children (5 to 17 years) of age) with severe acute asthma (forced expiratory volume in 1 second (FEV1), < 50% of the predicted value) were enrolled into a randomized double-blind three-arm placebo-controlled trial comparing three groups: group 1, three doses of nebulized ipratropium bromide within 60 minutes (250 micrograms/dose); group 2, one dose of ipratropium; group 3, no ipratropium. All patients were also treated with three doses of nebulized albuterol within 60 minutes (0.15 mg/kg per dose). Pulmonary function and clinical measures were assessed every 20 minutes for up to 120 minutes. RESULTS: The groups were comparable at baseline. At 120 minutes, the mean percentage of predicted FEV1 improved from 33.4% to 56.7% in group 1, from 34.2% to 52.3% in group 2, and from 35.4% to 48.4% in group 3 (p = 0.0001). The differences between groups were larger in those children with a baseline FEV1 < or = 30% of the predicted value: FEV1 increased from 24.5% to 50.9% in group 1, from 25.0% to 39.8% in group 2, and from 25.9% to 36.5% in group 3 (p = 0.0001). In group 1, 38% of the patients were hospitalized after the study, 44% in group 2, and 46% in group 3 (p value not significant). However, in patients with FEV1 < or = 30%, the hospitalization rates were 27% in group 1, 56% in group 2, and 83% in group 3 (p = 0.027). There were no toxic effects attributable to ipratropium. CONCLUSION: The addition of repeated doses of nebulized ipratropium to frequent high-dose albuterol therapy in patients with acute severe asthma is both safe and more effective than albuterol alone; its use in patients with very severe asthma may reduce hospitalizations.

Acute Disease↗
PubMed1995

Compromised cerebral blood flow reactivity is a predictor of stroke in patients with symptomatic carotid artery occlusive disease.

PURPOSE: The purpose of this study was to determine whether the hemodynamic consequences of extracranial carotid disease correlate with the risk of subsequent cerebral infarction. METHODS: In 95 patients with symptoms who had greater than or equal to 70% stenosis (31 patients) or who had occlusion (64 patients) of the ipsilateral carotid artery, cerebral blood flow was measured by the stable xenon/computed tomography technique both at baseline and after vasodilatory challenge with intravenous acetazolamide. Patients were stratified into group 1, 43 patients with no more than a 5% decrease in flow in any vascular territory, and group 2, 52 patients with greater than a 5% decrease in one or more vascular territories after an acetazolamide challenge. RESULTS: In group 2, 15 (28.9%) of 52 patients had a new stroke, but only one (2.3%) of 43 patients in group 1 did (p = 0.0005). Of patients with total carotid occlusion 10 (26%) of 38 in group 2 and none (0%) of 26 in group 1 had a new stroke (p = 0.003). Of patients with greater than or equal to 70% stenosis, five (36%) of 14 in group 2 and only one (6%) of 17 in group 1 had a stroke (p = 0.067). CONCLUSION: The loss of cerebral reactivity in patients with symptoms who had greater than or equal to 70% carotid stenosis or occlusion is an important predictor of impending cerebral infarction.

Acetazolamide↗
PubMed1995

A second locus for hereditary hemorrhagic telangiectasia maps to chromosome 12.

Hereditary hemorrhagic telangiectasia (HHT) or Osler-Rendu-Weber (ORW) disease is an autosomal dominant vascular dysplasia. Initial linkage studies identified an ORW gene localized to 9q33-q34 but with some families clearly excluding this region. A probable correlation in clinical phenotype between the 9q3-linked families and unlinked families was described with a significantly lower incidence of pulmonary arteriovenous malformations observed in the unlinked families. In this study we examined four unrelated ORW families for which linkage to chromosome 9q33-q34 has been previously excluded. Linkage was established for all four families to markers on chromosome 12, with a combined maximum lod score of 10.77 (theta = 0.04) with D12S339. Mapping of crossovers using haplotype analysis indicated that the candidate region lies in an 11-CM interval between D12S345 and D12S339, in the pericentromeric region of chromosome 12. A map location for a second ORW locus is thus established that exhibits a significantly reduced incidence of pulmonary involvement.

Chromosome Mapping↗
PubMed1995

Linear intracerebral calcification after depth electrode implantation.

We report linear calcifications along the trajectories of previously implanted depth electrodes in 2 patients. A 20-year-old man and a 38-year-old woman with medically intractable complex partial seizures (CPS), underwent bilateral frontal and mesiotemporal depth electrode implantation as part of their epilepsy surgery workup. Brain computed tomography (CT) at that time was normal (except for cerebrellar atrophy in one case). One patient had a left anterotemporal lobectomy (ATL), and the other declined operation. Subsequent CT scans showed linear calcifications 1-2 cm long in the occipital lobes (unilateral in 1 and bilateral in the other) that followed the trajectories of the temporal depth electrodes. This finding remained unchanged at latest follow-up (2-2.5 years), and no new pathology has appeared on subsequent scans. No abnormalities of calcium metabolism were detected. Review of all available CT scans of our patients with a history of previous depth electrode implantation showed no additional similar cases. We believe this is the first report of intracerebral calcifications after depth electrode implantation.

Adult↗
PubMed1995

Development of a PCR protocol for sensitive detection of Cryptosporidium oocysts in water samples.

The development of a reliable method of using PCR for detection of Cryptosporidium oocysts in environmental samples with oligonucleotide primers which amplify a portion of the sequence encoding the small (18S) subunit of rRNA producing a 435-bp product was demonstrated. The PCR assay was found to provide highly genus-specific detection of Cryptosporidium spp. after release of nucleic acids from oocysts by a simple freeze-thaw procedure. The assay routinely detected 1 to 10 oocysts in purified oocyst preparations, as shown by direct microscopic counts and by an immunofluorescence assay. The sensitivity of the PCR assay in some seeded environmental water samples was up to 1,000-fold lower. However, this interference was eliminated by either flow cytometry or magnetic-antibody capture. Sensitivity was also improved 10- to 1,000-fold by probing of the PCR product on dot blots with an oligonucleotide probe detected by chemiluminescence. Confirmation of the presence of Cryptosporidium oocysts in water samples from the outbreak in Milwaukee, Wis., was obtained with this technique, and PCR was found to be as sensitive as immunofluorescence for detection of oocysts in wastewater concentrates.

Animals↗
PubMed1995

A gene for familial venous malformations maps to chromosome 9p in a second large kindred.

Venous malformations are a common form of vascular anomaly that cause pain and disfigurement and can be life threatening if they involve critical organs. They occur sporadically or in a familial form, where multiple lesions are usually present. We have identified a large kindred showing autosomal dominant inheritance of venous malformations. Using this family we confirm linkage of a familial form of venous malformations to chromosome 9p. We suggest that blue rubber bleb naevus syndrome can be considered a particular manifestation of this form of familial venous malformations. The candidate region for this gene encompasses the interferon gene cluster and the MTS1 (p16) tumour suppressor gene.

Chromosome Mapping↗
PubMed1994

Effect of exogenous fatty acids with greater than 22 carbon atoms (very long chain fatty acids) on superoxide production by human neutrophils.

The effects of exogenous long chain fatty acids (LCFA) and very long chain fatty acids (VLCFA) on superoxide production by human neutrophils were compared. Superoxide production was greater and more rapid in response to arachidonic (20:4 (n-6)), eicosapentanoic (20:5 (n-3)), and docosahexanoic (22:6 (n-3)) acids than for triacontatetranoic (30:4 (n-6)), dotriacontatetranoic (32:4 (n-6)), and tetratriacontahexanoic (34:6 (n-3)) acids, although all of these fatty acids gave responses larger than FMLP. A similar decline in activity with increasing carbon chain length was observed for the monoenoic VLCFA (22:1 (n-9) to 34:1 (n-9)). 32:4 (n-6) did not affect responses to a maximally stimulatory concentration of 20:4 (n-6). However, the simultaneous addition of 20:4 (n-6) and 30:4 (n-6) gave additive responses if suboptimal dosages of 20:4 (n-6) were used. This suggests that the LCFA and VLCFA may use the same signal transduction systems. In addition, 30:4 (n-6) was only 10% as effective as was 20:4 (n-6) at gaining access to the organic solvent extractable cellular fraction. This figure correlated with the relative biologic potency of 20:4 (n-6) and 30:4 (n-6), suggesting that the extent of association with the cell may regulate the biologic activity of the fatty acids. The saturates, arachidic (20:0) and cerotic (26:0) acids, were either inactive or poor activators in all assay systems examined. The failure of 20:0 to induce superoxide production and the lower responses to 30:4 (n-6) and 34:6 (n-3) were not because of extracellular Ca2+, because the biologic potency of these fatty acids was not greatly enhanced by removing Ca2+ from the extracellular medium. In contrast, 20:4 (n-6)- and 22:6 (n-3)-induced superoxide production was markedly increased under Ca(2+)-free conditions.

Calcium↗
PubMed1994

Differences in the metabolism of eicosatetraenoic (20:4(n - 6)), tetracosatetraenoic (24:4(n - 6)) and triacontatetraenoic (30:4(n - 6)) acids in human neutrophils.

The metabolism of [1-14C]eicosatetraenoic (arachidonic, 20:4(n - 6)), [1-14C]tetracosatetraenoic (24:4(n - 6)) and [1-14C]triacontatetraenoic (30:4(n - 6)) acids was studied in intact human neutrophils. [1-14C]20:4(n - 6) and [1-14C]24:4(n - 6) were efficiently taken up by the neutrophils, esterified into neutral lipids and phospholipids, and elongated by up to four carbon units. In contrast, [1-14C]30:4(n - 6) was poorly incorporated into the cells and remained predominantly in the original unesterified form. The [1-14C]tetraenoic fatty acids were mainly esterified into triacylglycerol, suggesting that this lipid class is important in the intracellular trafficking of polyunsaturated fatty acids. The leukocytes demonstrated a low capacity to beta-oxidize and desaturate the fatty acid substrates. In the presence of calcium ionophore A23187 the neutrophils converted [1-14C]20:4(n - 6) to a variety of radiolabelled oxygenated fatty acid derivatives including prostaglandins, thromboxanes, mono- and dihydroxylated fatty acids and leukotrienes. The major eicosanoid products were 5-monohydroxy-20:4(n - 6) and leukotriene B4. In contrast, [1-14C]24:4(n - 6) was metabolized to radiolabelled monohydroxylated fatty acids (predominantly the 9-hydroxy positional isomer) but not to other lipoxygenase or cyclooxygenase products by the calcium ionophore-stimulated cells. Negligible oxygenated fatty acid compounds were formed from [1-14C]30:4(n - 6), indicating that it is a poor substrate for the neutrophil cyclooxygenase and lipoxygenase enzymes.

Arachidonic Acid↗
PubMed1994

Management of pterygium with surgery and radiation therapy. The North Florida Pterygium Study Group.

PURPOSE: To compare our results in the management of pterygium using a higher total dose with other reported results. METHODS AND MATERIALS: Between 1971 and 1991, 690 patients were treated with complete surgical excision followed by beta irradiation for primary or recurrent pterygium. Of these patients, 129 had two or more areas involving both eyes for a total of 825 lesions treated. Only 17 patients (2%) had temporal lesions with the rest of the patients having nasal pterygia. All patients underwent complete surgical resection of the pterygium before undergoing radiation therapy. One hundred forty-nine patients had undergone previous surgical resection alone but developed recurrence. After surgical excision, all patients were treated with Strontium-90 applicators starting immediately within 24 hr of surgery. Our standard policy was six weekly applications, each delivering a surface dose of 1000 cGy. The total dose delivered was 6000 cGy. Minimum follow-up was 1 year with a median of greater than 8 years. RESULTS: There were only fourteen recurrences (1.7%) out of a total of 825 lesions treated. Nine of the fourteen patients received suboptimal therapy undergoing less than five applications of Strontium-90. There were no major complications. CONCLUSION: The combination of surgical excision followed by adequate Strontium-90 applications is highly effective in the management of pterygium. The optimal total dose appears to be in the range of 2000 cGy to 6000 cGy.

Adult↗