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Biomedical subjects

J Ferguson

Publications and source records attributed to J Ferguson.

At least 289 records · Page 16Linked to original sources

Terfenadine and placebo compared in the treatment of chronic idiopathic urticaria: a randomised double-blind study.

Terfenadine, a potent and non-sedative antihistamine, was shown to be effective in chronic idiopathic urticaria in a double-blind crossover placebo controlled trial. An oral twice daily 60 mg dose of terfenadine was given and itch and wheal parameters were assessed daily. Despite the overall effectiveness of terfenadine, a variable response was noted which was similar to that shown in previous studies with other antihistamines.

Adult↗

A study of cutaneous photosensitivity induced by amiodarone.

Amiodarone-induced cutaneous photosensitivity was studied in 12 subjects treated with the drug. The action spectrum for the abnormal response to sunlight was shown to be within the range of 335-460 (+/- 30) nm. The clinical features of the photosensitivity response suggested that it was most probably a phototoxic reaction, a conclusion supported by the results of in vitro studies which indicated activity mainly against cell membranes. Of the five in vitro models used, three--namely photohaemolysis, the inhibition of DNA synthesis in PHA stimulated lymphocytes and the killing of mouse peritoneal macrophages--provided unequivocal evidence of the phototoxic potential of both amiodarone and its major metabolite, desethylamiodarone. In each model desethylamiodarone produced a greater effect by a factor of between 2 and 10. In vitro, UV-B wavelengths produced a greater effect than UVA but the difference between the effective wavelengths in vivo and in vitro might be explained by the greater absorption of the shorter wavelength UV-B in the epidermis. Zinc oxide-containing preparations appeared to be the most effective in reducing the cutaneous photosensitivity. It is suggested that the long-term cutaneous pigmentation resulting from oral amiodarone has a significant photosensitivity component.

Adult↗

Lymphocyte subsets and Langerhans cells in allergic and irritant patch test reactions: histometric studies.

This study has attempted to distinguish between allergic and irritant reactions to patch tests by semiquantitative histological methods. The extent of perivascular chronic inflammatory infiltrate at 72 h in irritant patch test reactions to sodium lauryl sulphate was shown to be small and very consistent, whereas in allergic reactions to nickel sulphate it was generally larger and more variable in size (p less than 0.02). The two major lymphocyte subsets (T4 and T8) were randomly intermixed in both types of reaction and formed the major component of both the perivascular and diffuse dermal infiltrate, without any evidence of selective migration. The T4:T8 ratios were similar in focal and diffuse infiltrates. The number of T6 dendritic (putative Langerhans) cells in the epidermis (per mm inner epidermal length) was usually greatly reduced in irritant reactions (5-16 mm-1, mean 10 mm-1) but remained within normal limits in allergic reactions (6-33 mm-1, mean 21 mm-1) (p less than 0.001). Comparable results were seen with other irritants (mercuric chloride and benzalkonium chloride) and other allergens (neomycin sulphate, ethylene diamine and potassium dichromate). In additional experiments, pairs of biopsies were taken from the reaction and from adjacent unaffected skin. The T6 cell density in the epidermis did not significantly differ between allergic reactions and control skin. By contrast, the irritant reactions had fewer T6 cells than the control skin (p less than 0.001).

Dermatitis, Atopic↗

A study of compositae plant extract reactions in photosensitivity dermatitis.

In subjects with chronic photosensitivity of the photosensitivity dermatitis/actinic reticuloid type the persistent reaction of the skin appears to be due to a number of factors, including those of contact allergic sensitivity and of photosensitivity (i.e., phototoxicity and/or photoallergy). The assessment of the relevant importance of these factors can be complicated by the reactivity of the skin resulting in false positive responses from skin patch and photopatch testing. Moreover, difficulties may also arise in the assessment of the results using commercially available patch test materials. However, the study described here indicated that, provided the reactivity of the skin is suppressed prior to investigation, reliable results are obtained from photopatch testing and that these results are similar whether the extract is from a commercial source or has been obtained from locally grown Compositae plants. Also, that although there may be a photoallergic component in the cutaneous photosensitivity, the results of the in vivo and in vitro studies reported here indicate the likely involvement of phototoxicity as well.

Adult↗

Histometric study of the localisation of lymphocyte subsets and accessory cells in human Mantoux reactions.

Intradermal injection of purified protein derivative produced typical delayed type hypersensitivity reactions in five healthy human subjects. The major subpopulations of lymphocytes and certain accessory cells were located in frozen sections of biopsies of the lesions with monoclonal antibodies and immunohistochemical staining. The densities (expressed as number/unit area for comparison) of the different types of cells were counted at various microanatomical locations in the tissue. The inflammatory cells were concentrated in narrow zones, initially (24 h) only surrounding small blood vessels but later (48-96 h) also around sweat ducts. Lymphocytes were the predominant cell type at these sites with T4 and T8 cells randomly intermixed at a ratio similar to that in the mononuclear cell fraction of the peripheral blood samples removed at the time of biopsy. There was also a scanty diffuse infiltrate in the intervening dermis, but here the T4:T8 ratio was significantly lower than that in the peripheral blood or perivascular cuffs. There was considerable intersubject variation in the relative preponderance of T8 cells in the diffuse infiltrate. The results suggest that there is no subset selection in the initial emigration of lymphocytes through vascular endothelium in the delayed hypersensitivity reaction, but that the subsets behave differently during the subsequent migration through the tissues. It remains to be determined whether the extent to which T8 cells migrate more rapidly than T4 cells through the tissues may influence the reaction at the site of entry of organisms or antigens into the body by altering the balance of the immunoregulatory lymphocyte subsets. This may underlie some of the differences in susceptibility to infection between subjects and determine the type of granuloma that develops in a particular patient.

Adult↗

Correlative electrocardiographic studies in myocardial infarction.

The electrocardiogram remains our first and most widely available tool to study myocardial infarction. We have attempted to suggest that we must be both more circumspect and adventurous in its use. The traditional electrocardiographic labels imply a level of precision that is unwarranted and so obscure real, often clinically important differences that exist among patients. We believe the electrocardiogram becomes more powerful when it is used with other noninvasive tests, and all such tests are best interpreted within rather than removed from the clinical context. We suggest as well that frequently after infarction, zones of viable muscle exist that are still vulnerable to ischemia. These zones may lie within or be remote from the actual infarct region, and noninvasive tests should be milked for clues that these regions are present, for while there is little to be done for necrotic tissue after infarction, there is considerable therapy available, both medical and surgical, to rescue tissue at risk of ischemia after infarction.

Electrocardiography↗

mRNA levels for the fermentative alcohol dehydrogenase of Saccharomyces cerevisiae decrease upon growth on a nonfermentable carbon source.

The classical, fermentative alcohol dehydrogenase from Saccharomyces cerevisiae, which previously was thought to be constitutive, has been shown to be repressed by growth on nonfermentative carbon sources. The rate of alcohol dehydrogenase I protein synthesis declined 6-fold within 3 to 4 after yeast were transferred from medium containing glucose to medium containing ethanol, and it declined 10-fold after glucose became depleted from the medium during diauxic growth. The decreased rate of alcohol dehydrogenase I protein synthesis was shown not to be the result of an increased rate of degradation of the alcohol dehydrogenase I protein. The decline in alcohol dehydrogenase I protein synthesis was correlated with a 6- to 10-fold decrease in the amount of functional alcohol dehydrogenase I mRNA within 3 to 4 h after transfer from glucose-containing medium to medium containing ethanol. A similar decrease in alcohol dehydrogenase I functional mRNA occurred when cells were depleted of glucose by diauxic growth. Total alcohol dehydrogenase I mRNA, as detected by hybridization to the cloned ADC1 gene, was found in the same relative abundance as the amount of translatable alcohol dehydrogenase I mRNA during the different growth conditions. These results suggest that the alcohol dehydrogenase I protein is transcriptionally regulated.

Alcohol Dehydrogenase↗

Isolation and transcriptional characterization of three genes which function at start, the controlling event of the Saccharomyces cerevisiae cell division cycle: CDC36, CDC37, and CDC39.

The genes CDC36, CDC37, and CDC39, thought to function in the cell division control process in Saccharomyces cerevisiae, were isolated from a recombinant plasmid library prepared by partial digestion of S. cerevisiae genomic DNA with Sau3A and insertion into the S. cerevisiae-Escherichia coli shuttle vector YRp7. In each case, S. cerevisiae DNA sequences were identified which could complement mutant alleles of the gene in question and which could direct integration of a plasmid at the chromosomal location known to correspond to that gene. Complementing DNA segments were subcloned to remove extraneous coding regions. The coding regions corresponding to CDC36, CDC37, and CDC39 were then identified and localized by R-loop analysis. The estimated sizes of the three coding regions were 615, 1,400, and 2,700 base pairs, respectively. Transcriptional orientation of the coding regions was established by using M13 vectors to prepare strand-specific probes followed by hybridization to blots of electrophoresed S. cerevisiae mRNA. The intracellular steady-state abundance of the mRNA species corresponding to the genes was estimated by comparing hybridization signals on RNA blots to that of a previously determined standard, the cell cycle start gene CDC28. The quantities calculated for the three mRNA species were low, ranging from 1.5 +/- 1 copies per haploid cell for the CDC36 mRNA to 3.1 +/- 1.5 and 4.6 +/- 2 copies per haploid cell for the CDC37 and CDC39 mRNAs, respectively. The CDC28 mRNA had been previously estimated at 7.0 +/- 2 copies per cell.

Cell Cycle↗

Accidental hypothermia.

The diagnosis of hypothermia rests solely upon a measured core temperature of 35 degrees C or less; a special thermometer calibrated to record low temperatures should be used whenever hypothermia is suspected. Hospital management of the hypothermic patient consists of definitive rewarming therapy.

Accidents↗

The relationship between exposure to fragrance materials and persistent light reaction in the photosensitivity dermatitis with actinic reticuloid syndrome.

Contact allergic sensitivity to allergens such as plants of the Compositae family is a feature of the chronic skin reaction seen in the photosensitivity dermatitis with actinic reticuloid syndrome. In fifty patients with this syndrome an increased incidence of contact allergic sensitivity to some common fragrance materials was demonstrated. Evidence is also presented, both by in vitro and in vivo studies, which indicates that a phototoxic mechanism is involved. The relevance of continued exposure to common allergens and their involvement in photosensitization mechanisms is discussed in an attempt to explain the state of 'persistent light reaction'.

Humans↗

Preliminary characterization of the transcriptional and translational products of the Saccharomyces cerevisiae cell division cycle gene CDC28.

The CDC28 gene was subcloned from a plasmid containing a 6.5-kilobase-pair segment of Saccharomyces cerevisiae DNA YRp7(CDC28-3) by partial digestion with Sau3A and insertion of the resulting fragments into the BamHI sites of YRp7 and pRC1. Recombinant plasmids were obtained containing inserts of 4.4 and 3.1 kilobase pairs which were capable of complementing a cdc28(ts) mutation. R-loop analysis indicated that each yeast insert contained two RNA coding regions of about 0.8 and 1.0 kilobase pairs, respectively. In vitro mutagenesis experiments suggested that the smaller coding region corresponded to the CDC28 gene. When cellular polyadenylic acid-containing RNA, separated by agarose gel electrophoresis after denaturation with glyoxal and transferred to nitrocellulose membrane, was reacted with labeled DNA from the smaller coding region, and RNA species of about 1 kilobase in length was detected. Presumably, the discrepancy in size between the R-loop and electrophoretic determinations is due to a segment of polyadenylic acid which is excluded from the R-loops. By using hybridization of the histone H2B mRNAs to an appropriate probe as a previously determined standards, it was possible to estimate the number of CDC28 mRNA copies per haploid cell as between 6 and 12 molecules. Hybrid release translation performed on the CDC29 mRNA directed the synthesis of a polypeptide of 27,000 daltons, as determined by polyacrylamide gel electrophoresis in sodium dodecyl sulfate. This polypeptide was not synthesized when mRNA prepared from a cdc28 nonsense mutant was translated in a parallel fashion. However, if the RNA from a cell containing the CDC28 gene on a plasmid maintained at a high copy number was translated, the amount of in vitro product was amplified fivefold.

Base Sequence↗

[Use of the ECG under physical load for assessing the status of ischemic heart disease patients].

To determine to what extent the diagnostic accuracy of stress testing is influenced by the prevalence of coronary artery disease, we correlated the description of chest pain, the ST-segment response to exercise, and the results of coronary arteriography in 1465 men and 580 women from the registry for the Coronary Artery Surgery Study (CASS). A positive ST-segment response increased the pre-test risk by only 7 to 20%, whereas a negative ST-segment response decreased the risk by only 2 to 28%. Although the percentage of false positive results differed between men and women (12 +/- 1% vs 53 +/-- 3%, p less than 0.001), this difference was not seen in a subgroup matched for prevalence of coronary artery disease. Thus, the ability of stress testing to predict coronary artery disease is limited in a heterogenous population in which the prevalence of disease can be estimated through classification of chest pain and the sex of the patient. Additional multivariant linear discriminant function analysis on treadmill and angiographic data from 500 men with definite angina, 584 men with probable angina and 267 men with nonspecific chest pain identified independent predictors of presence and extent of coronary disease. The discriminant function developed clinical, and clinical and exercise risk indices for each patient subset. Probability curves demonstrated that exercise testing provided more diagnostic information than clinical data alone in patients with definite and probable angina. However, exercise testing in men with nonspecific chest pain was of limited value since disease prevalence was already low. We conclude that (a) analysis of the ST-segment response to exercise provides limited information regarding the diagnosis of coronary artery disease when used alone, and (b) use of other exercise variables in addition to clinical data improves the diagnostic ability of the exercise test in men with definite or probable angina.

Angina Pectoris↗