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Biomedical subjects

J Clarke

Publications and source records attributed to J Clarke.

At least 271 records · Page 15Linked to original sources

Measurement of anti-DNA antibodies: a reappraisal using five different methods.

One hundred and thirty coded sera, 60 from patients with systemic lupus erythematosus (SLE) and 70 from patients with other autoimmune rheumatic diseases were tested for deoxyribonucleic acid (DNA) binding activity by five different types of assay. These were enzyme linked immunosorbent assay (ELISA) (distinguishing IgG and IgM anti-ssDNA and anti-dsDNA), Crithidia luciliae, a nitrocellulose filter assay, the Amersham kit, and another modified Farr assay, the radioimmunoassay (RIA) (UK). The Crithidia test was the most specific, none of the controls was positive, but the least sensitive (13% positive only). The RIA (UK) was the most sensitive (57% positive). In most of the assays 3-9% of the controls were positive. When the SLE sera were analysed according to disease activity the IgG anti-dsDNA ELISA, all three RIA values, and the Crithidia test values were raised in all the patients with severely active disease. Some patients with inactive disease, however, were positive in each of the tests. The best interassay correlations (r less than 0.49) were found between RIA (UK), and ss IgG and the Amersham kit; and between ds IgG and ss IgG. In the main, however, it was clear that different assays are dependent upon distinctive properties of DNA antibodies. It seems inevitable that most major rheumatology units will require more than one anti-DNA antibody assay.

Adolescent↗

Fine needle aspiration cytology, with immediate reporting, in the outpatient diagnosis of breast disease.

One hundred and fifty one new patients attending a breast clinic over a 6 month period underwent fine needle aspiration cytology (FNAC), with immediate reporting of the smears in the clinic. Thirty nine smears (25.8%) were classified as unequivocally malignant, 10 (6.6%) as being suspicious of malignancy, 61 (40.3%) as benign and 41 (27.1%) were acellular. There were no false positive diagnoses and only one false negative cytological diagnosis of breast cancer [corrected]. Immediate reporting of results enabled the diagnosis to be discussed with the patient at the first attendance and allowed improved surgical management of both benign as well as malignant breast disease.

Adult↗

The SV40 enhancer is composed of multiple functional elements that can compensate for one another.

We present evidence that the SV40 enhancer consists of three functional units, A, B, and C, each of which can cooperate with the others or with duplicates of itself to enhance transcription. We show that, when element C, containing the core consensus sequence, is inactivated by point mutations, revertants with restored enhancer function contain duplications of either one or both of the elements A and B. To search for additional elements, we isolated revertants of a mutant with the three elements mutated. These revertants do not identify any other elements; instead, enhancer function is effectively restored by "double duplications," in which the first duplication event either partially or entirely recreates one of the three elements A, B, and C and the second duplication then creates two copies of the newly created sequence.

Base Sequence↗

Analysis of the physiological stress profile: the interrupted time-series design.

Most research employing physiological stress profiling procedures has relied upon statistical analyses that are flawed in two ways: These analyses typically average the physiological levels observed across a series of observations during any one phase of the profile, thereby ignoring rate of change as a relevant parameter, and the problem of autocorrelation, or the natural correlation of time-series observations of the same physiologic activity, is unaddressed. We hope to introduce the biofeedback field to the technique of interrupted time-series analysis, which effectively deals with these two flaws. Interrupted time-series analysis additionally permits statistical conclusions based upon the stress profile of a single individual, thereby providing an objective basis for decisions concerning the effectiveness of training or the timing of changes in training for a single client. We describe the application of the technique to the analysis of a stress profile of a subject diagnosed as hypertensive.

Adult↗

Novel modified beta-interferons: gene cloning, expression, and biological activity in bacterial extracts.

A series of novel, modified interferons based on the structure of human beta-interferon have been expressed in Escherichia coli. Modified interferon genes were constructed from sequences derived from the natural beta-interferon gene, a synthetic beta-interferon gene, or a specific combination of the two. A total of 23 out of the 25 novel interferons exhibited antiviral (AV) and antiproliferative (AP) activity which varied from 3 to 230% and 8 to 490% of the values for beta-interferon, respectively. None of the novel interferons had only AV or AP activity, although one had a much reduced ratio of AV/AP activity compared with beta-interferon. Substitution of beta-interferon amino acids 2-7 or 28-46 resulted in interferons with significantly increased AP activity on Daudi lymphoblastoid cells (four- to fivefold). All the novel interferons except two with modifications in the 82-105 region reacted with a neutralizing beta-interferon monoclonal antibody.

Amino Acid Sequence↗

Mortality in patients of the Glasgow Blood Pressure Clinic.

The mortality of 3783 non-malignant hypertensive patients attending the Glasgow Blood Pressure Clinic between 1968 and 1983 and followed for an average of 6.5 years was compared with that in three control groups: the general population of Strathclyde a group of 15 422 subjects aged 45-64 years and screened in Renfrew and Paisley between 1972 and 1976, and a group of hypertensives seen in a blood pressure clinic based on general practice in Renfrew. Average blood pressure for men at entry to the Glasgow Clinic was 181/111 mmHg falling to 158/96 mmHg during treatment. Corresponding values for women were 185/109 mmHg and 161/96 mmHg. Seven hundred and fifty clinic patients (451 males) died during follow-up, the commonest causes of death in both sexes being myocardial infarction and stroke. All-cause age-adjusted mortality (deaths per 1000 patient-years) was 41.4 for men and 22.1 for women. At all ages in both sexes and for all levels of initial blood pressure mortality was less in patients whose blood pressure was reduced most. Without a randomized control group it is not certain that lower mortality in those with well controlled blood pressure was due to treatment, although this is the most likely explanation. Cigarette smoking, a history of myocardial infarction, angina or stroke, retinal arterio-venous nipping, raised blood urea, an abnormal electrocardiogram (ECG) and secondary hypertension were associated with increased risk, but heavy alcohol intake, obesity, haematocrit greater than 45%, hypokalaemia and social class were not. Life table analysis showed that, despite some reduction of mortality by treatment, the relative risk to men and women in the clinic remained two- to five-times that of the general population. The benefits of treatment were not such as to restore normal expectation of life even when blood pressure was well controlled. Excess mortality in the clinic could not be explained by difference of smoking habit or social class. This suggests that there is in the hypertensive patients of the Glasgow Clinic an element of irreducible risk, that treatment may be beneficial in some respects but harmful in others, or that patients at particularly high risk are selectively referred to the clinic.

Actuarial Analysis↗

Diabetes mellitus and primary hepatocellular carcinoma.

In view of the increasing incidence of primary hepatocellular carcinoma in western Europe and concern that this may in part be related to long-term use of drugs which cause hepatic microsomal enzyme induction, we undertook a comparison of long-term drug use in 105 patients with hepatocellular carcinoma and equal numbers of age and sex-matched patients with colorectal tumours and with fractures of femur. We found no patients with hepatocellular carcinoma who were long-term anticonvulsant users and only one who used oral contraceptives. However, we observed a four-fold excess of diabetic patients among the group with hepatocellular carcinoma. This association did not appear to be due to pre-existing haemochromatosis, alcoholic cirrhosis or viral hepatitis. The association was strongest in patients receiving drug treatment for diabetes, but the data, although suggestive, were insufficient to determine whether any specific anti-diabetic agent could be responsible. Further studies are required to elucidate the nature of this unexpected association. An association of this magnitude with diabetes mellitus could account at least in part for the increasing incidence of hepatocellular carcinoma in western Europe.

Adult↗

Non-adherent, low-density cells from human peripheral blood contain dendritic cells and monocytes, both with veiled morphology.

Dendritic cells (DC) from human peripheral blood, known to adhere transiently and to become non-adherent by 16 hr, can be separated in the low-density interface on hypertonic Metrizamide gradients. Many more low-density cells (5.8% of the mononuclear cells separated on Ficoll) were obtained from the population that was non-adherent after only 90 min. Over 95% of these low-density cells had veiled morphology. A proportion were monocytes by phenotypic and phagocytic properties. One-third of the cells (on average) were DC on the basis of lack of monocyte phenotype and of potency as stimulators in the mixed lymphocyte reaction. Including both the 16 hr and 90 min non-adherent cells, over 2% of the mononuclear cells isolated from human peripheral blood may be DC.

5'-Nucleotidase↗