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Biomedical subjects

K Johnston

Publications and source records attributed to K Johnston.

At least 91 records · Page 5Linked to original sources
PubMed1990

Measurement of peptidoleukotrienes in biological fluids.

Samples of human bronchoalveolar lavage fluid (BALF) and urine were utilized to demonstrate methods for quantitation and validation of leukotrienes (LTs). These methods utilize an enzyme immunoassay (EIA) that uses commercially available reagents, the antibody recognizing LTC4, LTD4, LTE4, and N-acetyl LTE4. BALF containing epithelial lining fluid was collected from atopic asthmatics both before and 5 min after the subjects had been challenged with a local instillation of allergen into the airways. BALF samples collected without allergen challenge had low levels of immunoreactive LTs, whereas samples collected after allergen were markedly elevated. After high-performance liquid chromatography (HPLC) separation of LTs, EIA revealed the presence of LTC4. The identity was validated by incubating LTC4 with a bovine gamma-glutamyl transpeptidase with dipeptidase activity that converted added [3H]-LTC4 as well as LTC4 immunoreactivity to LTE4. Urine samples collected from six healthy volunteers, one patient with adult respiratory distress syndrome (ARDS), and three patients in status asthmaticus were also analyzed for LTs. After HPLC separation of LTs and quantitation by EIA, urine samples from healthy subjects were found to have low but measurable LTE4. In contrast, the urine samples from the patients in status asthmaticus and from the ARDS patient had large elevations of LTE4 levels compared with healthy subjects. When the HPLC fractions containing [3H]LTE4 and LT immunoreactivity in the ARDS sample were treated with acetic anhydride, HPLC analysis indicated that both radiolabel and immunoreactivity now eluted at the retention time of N-acetyl LTE4, the derivatized product of LTE4. The methods described are relatively easy and can be used to measure and validate the existence of peptidoleukotrienes in biological samples.

Bronchoalveolar Lavage Fluid↗
PubMed1990

Elevated levels of leukotriene C4 in bronchoalveolar lavage fluid from atopic asthmatics after endobronchial allergen challenge.

Sulfidopeptide leukotrienes have been implicated in the pathogenesis of asthma because of their ability to induce bronchospasm, airways hyperreactivity, and increased mucus production. In the present study, the leukotrienes (LT) C4, D4, and E4 were measured in bronchoalveolar lavage fluid (BALF) before and 5 min after endobronchial allergen challenge in four subject groups: nonatopic nonasthmatic, nonatopic asthmatic, atopic nonasthmatic, and atopic asthmatic. As determined by high performance liquid chromatography (HPLC), after allergen challenge, the predominant sulfidopeptide leukotriene found in BALF from atopic asthmatics was LTC4. Smaller amounts of LTD4 and LTE4 were detectable. The baseline level of leukotrienes in the atopic asthmatics was 64 +/- 18 pg/ml, with measurable levels being found in nine of 11 samples. Atopic nonasthmatics had measurable levels in only one of seven baseline samples, whereas five of six nonatopic subjects had undetectable levels. Allergen challenge in atopic asthmatics resulted in significant increases in LTC4 over prechallenge levels (64 +/- 18 to 616 +/- 193 pg/ml) (p less than 0.01) and over levels in the three control groups after challenge (p = 0.0297). The atopic nonasthmatic group also had detectable leukotriene levels after allergen challenge (88 +/- 32 pg/ml), whereas leukotrienes remained undetectable in five of the six nonatopic samples. For comparison, histamine and the prostanoids prostaglandin D2 (PGD2) and thromboxane B2 (TxB2) were also measured in BALF. The levels of all three of these mediators increased in BALF from atopic asthmatics after allergen challenge. After allergen challenge, the best correlation was found between the levels in BALF for the prostanoids PGD2 and TxB2 (r = 0.88).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

3-Hydroxy-3-methylglutaryl-CoA lyase deficiency as detected by radiochemical assay in cell extracts by thin-layer chromatography, and identification of three new cases.

In this rapid radiochemical assay for 3-hydroxy-3-methylglutaryl-coenzyme A lyase (I) activity in cell extracts, DL-3[glutaryl-3-14C]hydroxy-3-methylglutaryl-coenzyme A is used as substrate and the radiochemical product, [3-14C]acetoacetic acid, is converted to the more stable [3-14C]-3-hydroxybutyric acid in the presence of added NADH and 3-hydroxybutyrate dehydrogenase. Substrate and product are separated and quantified by thin-layer chromatography on cellulose (solvent system: butanol/water/formic acid, 77:13:10 by vol). All reagents for the assay are commercially available. No detailed column chromatography or spectrophotometry is required. Thus the assay is suited for any clinical laboratory. Using this procedure, we studied cultured fibroblasts or lymphocytes isolated from whole blood from five patients in whom the urinary organic acid profile was suggestive of deficiency of I. Three patients had less than or equal to 18% of control I activity in fibroblast or lymphocyte extracts. The other two had activity within the normal range. In one of the latter cases, urinary excretion of three of the characteristic acids disappeared with age, and 3-hydroxyisovaleric acid excretion was within normal limits. The other case presented with urinary excretion of moderate amounts of all four metabolites and the characteristic absence of urinary ketone bodies. Evidently, confirmatory enzyme studies should be undertaken, even when the profile of urinary organic acids appears definitive for this deficiency.

Cells, Cultured↗
PubMed1989

A non-centromeric C band variant on chromosome 11q23.2.

An extra G band was found inserted into chromosome 11q23.2 in a boy who had severe developmental delay and anal stenosis. Cytogenetic characterisation of this extra band showed that it was composed of Q band brilliant, C band heterochromatin. It was also present in clinically normal subjects in two other generations and was therefore presumed to be unrelated to the clinical abnormalities in the proband. Although rare, this cytogenetic anomaly may be useful as a genetic marker for 11q23.2.

Abnormalities, Multiple↗
PubMed1988

New DNA guidelines.

Explore the source record for details and available documents.

Advisory Committees↗
PubMed1987

3'-Azido-3'-deoxythymidine in feline leukemia virus-infected cats: a model for therapy and prophylaxis of AIDS.

Due to similarities between human immunodeficiency virus and feline leukemia virus, the etiological agents of acquired immunodeficiency syndromes in humans and cats, the feline system was used as a model to conduct preliminary investigations as to the efficacy of the thymidine analogue 3'-azido-3'-deoxythymidine (AZT) as a therapeutic and preventive agent against retroviruses. In vitro evaluations of AZT cytotoxicity and its antiviral effects were conducted. Subsequently, 50 6-week-old specific pathogen free kittens were inoculated with a highly immunosuppressive strain of Richard-Feline Leukemia Virus. These cats were randomly subdivided into smaller groups with initiation of AZT treatment at variable times postinfection. All animals were periodically monitored for circulating infectious virus particles and virus-neutralizing antibodies. Their clinical condition was closely followed throughout the 6-week AZT treatment phase and for several months thereafter. The results indicate that AZT prevents retrovirus infection if administered immediately following virus exposure, and may also reduce retrovirus replication if administered to previously infected animals. Some of the treated cats developed neutralizing antibodies against the virus and became resistant to subsequent viral challenge. Future trials with this drug, both for the prevention and treatment of retroviral diseases in humans and animals, are warranted.

Acquired Immunodeficiency Syndrome↗
PubMed1987

De novo X;Y translocation associated with imperforate anus and retinal pigmentary abnormalities.

Cytogenetically detectable translocations of Y chromosome material onto the distal short arm of an X chromosome are rare and result in a variable and poorly defined phenotype of short stature and short limbs occasionally associated with mental retardation. We report on a patient with a de novo 46,X,t(X;Y)(p22;q11) chromosome constitution who has additional features not previously described with this chromosome abnormality, including abnormal retinal pigmentation, imperforate anus, and hydronephrosis. Our patient extends the phenotype associated with X;Y translocations, raising new considerations for the clinical management and genetic counseling of such patients and their families.

Abnormalities, Multiple↗
PubMed1986

Alpha-thalassemia in Papua New Guinea.

A study of the distribution of alpha-thalassemia in Papua New Guinea (PNG) was carried out by DNA analysis. A total of 664 DNA samples were screened for alpha-thalassemia 2 and alpha-thalassemia 1 caused respectively by either deletion of one or both of the duplicated alpha-globin genes. alpha-Thalassemia 2 was detected in high frequencies in coastal and lowland regions where malaria has been holo- to hyperendemic but in low frequencies in non-malarious highland regions. The highest frequency was observed in the north coast of PNG. The distribution of alpha-thalassemia 2 seems to be in accordance with other conditions such as ovalocytosis and G6PD deficiency which are also prevalent in this population, suggesting that they may interact in protection against malaria. However, it appears to be negatively correlated with beta-thalassemia and alpha-thalassemia 1, the latter being extremely rare in this population. Analysis of the types and subtypes of the single alpha-globin gene deletion revealed a predominance of the -alpha 4.2 type in general, except in some regions in the south where the -alpha 3.7 type is prevalent. The -alpha 3.7 I subtype is the common form of the -alpha 3.7 deletion in the PNG mainland. The -alpha 3.7 III subtype, previously reported to be unique in Melanesians and Polynesians, was detected in an offshore island of PNG. However, this subtype is very rare in Melanesians from the PNG mainland.

Chromosome Deletion↗
PubMed1985

A point prevalence study of alcoholism and mental illness among downtown migrants.

Since the 1960s the bulk of America's mentally ill have been deinstitutionalized to the community. A number of these people now live in the downtown areas of large cities in close association with the established vagrant culture which includes a significant portion of alcohol abusers. The bizarre and impoverished nature of the lives of these formerly institutionalized mentally ill citizens, coupled with their propinquity to government and business establishments, creates a social policy dilemma. A point prevalence study design was used to ascertain the demographic, physical, mental illness and alcohol abuse characteristics of a sample of a vagrant population which inhabits the downtown area of an American Northwest urban community. Analysis of the data of a sample of vagrants who frequent an emergency shelter and a single residence occupancy hotel demonstrated that the two groups were similar. Participants were predominantly male, white and in their mid thirties. Forty percent had never married and over 50% were high school educated and possess labor skills. Grouped data indicates that, in view of the dearth of literature describing the relationship of mentally illness and alcohol abuse, the psychiatric and alcohol use behavior of deinstitutionalized populations requires further study.

Adult↗
PubMed1985

Acute chromium poisoning in a 2 year old child.

Sodium dichromate ingestion in children is uncommon and potentially lethal. The most appropriate management is uncertain because of the lack of sound data contained in the few reports of successfully treated patients. Immediate treatment should include urgent induction of emesis, administration of ascorbic acid as an antidote, followed by supportive treatment.

Antidotes↗
PubMed1984

Central hypoventilation syndrome in pyruvate dehydrogenase complex deficiency.

The presentation and treatment of a central hypoventilation syndrome in a boy with pyruvate dehydrogenase complex (PDHC) deficiency are reported. Dephosphorylated PDHC was assayed in disrupted fibroblasts after pretreatment with dichloroacetate, a pyruvate dehydrogenase kinase inhibitor. Maximal specific activity of activated patient PDHC was 10% to 30% of control values. Patient PDHC activity was not increased by alterations in concentrations of pyruvate or cofactors (thiamine pyrophosphate [TPP], coenzyme A [CoA], oxidized form of nicotinamide adenine dinucleotide [NAD+]). Clinically, normalization of plasma lactate by a high-lipid diet did not prevent slowly progressive neurologic decline. The patient manifested intermittent ataxia, episodic profound weakness, moderate psychomotor retardation, ophthalmoplegia, and retinal pigment epithelial changes. A true central hypoventilation syndrome was documented on the basis of rigorous radiologic, electrophysiologic, and pulmonary function criteria. Theophylline, progesterone, and ritalin neither altered ventilatory response to CO2 nor permitted weaning from the ventilator. In contrast, peripheral chemoreceptor stimulants (intravenous doxapram; oral almitrine) effected an acute doubling of minute ventilation with appropriate decreases in PaCO2. However, a positive response to long-term therapy with almitrine could not be unequivocally shown. It was concluded that measurement of disrupted fibroblast PDHC following dichloroacetate activation constitutes an accurate assay for PDHC deficiency. PDHC deficiency must be considered in the differential diagnosis of the central hypoventilation syndrome; this appears to be the first report of such an association. Finally, a therapeutic trial of a peripheral chemoreceptor agonist is warranted in the management of central hypoventilation syndrome.

Almitrine↗