Biomedical subjects
Publications and source records attributed to C Kay.
Two small peptide substrates for HIV-1 proteinase were synthesised. The sequences chosen were basically from that of the gag-pol protein, which is the natural substrate for the proteinase. To protect these peptides from the attack of exopeptidases, the N- and C-termini were suitably protected, which also makes these substrates specific to HIV-proteinase and eliminates the requirement for highly purified enzyme.
We show that rheumatoid arthritis (RA) serum or synovial fluid (SF) increases the growth capacity of normal, interleukin 2 (IL-2) driven cell preparations, compared to normal human serum (NHS). Proliferation in RA serum and SF cultures was primarily associated with expansion of natural killer (NK)-like cells (CD16+, CD57+), and in NHS cultures, with T cell (CD3+ CD4+ CD8+) growth. The capacity of RA serum to promote NK cell growth was related to patient global clinical activity and rheumatoid factor (RF) titers. The NK-like cells, but not the T-like cells, induced high levels of IgM RF synthesis in autologous B cells. Thus, alteration in NK cell growth may disrupt NK-B cell circuits in RA and contribute to B cell dysfunction (RF synthesis).
A colorimetric assay for HIV proteinase using small protected peptide substrates is described. Substrates are cleaved to release N-terminal prolyl peptides which react with isatin to form a blue product which is measured spectrophotometrically. The assay is suitable for use with pure enzyme or crude extracts derived from genetically engineered Escherichia coli.
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OBJECTIVE: To determine whether there is sufficient benefit to be gained by offering screening for breast cancer with mammography to women aged 65-79, who are not normally invited for screening. DESIGN: Pilot study of women eligible for screening but not for personal invitation. The results of this study were compared with the results of routinely screened younger women (aged 50-64) from the same general practice. SETTING: One group general practice in south Manchester. PATIENTS: The 631 women aged 65-79 on the practice list. A total of 42 (7%) were excluded by the general practitioner, and 22 (4%) invitation letters were returned by the post office. MAIN OUTCOME MEASURES: Response rates to invitation for screening assessed by three indices: crude population coverage ratio, crude invited population coverage ratio, and corrected invited population coverage ratio. RESULTS: 344 Patients aged 65-79 (61% of those invited, excluding those who could not be traced) were screened compared with 77% of women aged 50-64. The three response indices were higher for younger women than older: crude population coverage ratio = 66.5%, crude invited population coverage ratio = 69.3%, corrected invited population coverage ratio = 76.8% for women aged 50-64, compared with 54.5%, 58.4%, and 60.7% respectively for women aged 65-79. All four biopsies done in the older women gave positive results, giving a cancer detection rate of 11.6/1000 compared with 4.1/1000 among younger women. CONCLUSIONS: These results show that there is a potential for high attendance at routine screening by older women if they are invited in the same way as younger women. If these results are found elsewhere the costs and benefits of screening older women should be reassessed.
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Of 47,000 women followed since 1968, those who had used oral contraceptives (ever-users) had a significantly higher incidence rate of cervical cancer than never-users. After standardisation of rates by age, parity, smoking, social class, number of previously normal cervical smears, and history of sexually transmitted disease, the excess was 41 per 100,000 woman-years for carcinoma-in-situ and 8 per 100,000 woman-years for invasive cervical cancer. Incidence increased with increasing duration of use: the standardised incidence rate for cervical cancer in women who had taken the pill for more than 10 years was four times than in never-users. Ever-users had a lower incidence of other uterine cancers (deficit 5 per 100,000 woman-years); a lower incidence of ovarian cancer was also found (deficit 4 per 100,000), but was not statistically significant. Overall, ever-users had an excess incidence for genital tract cancers 37 per 100,000 woman-years. This excess was mainly from carcinoma-in-situ of the cervix; the excess incidence of invasive cervical cancer was offset by the deficits in other uterine and ovarian cancers. Standardised mortality rates from genital cancer were similar in ever-users and never-users. Of relevance to clinical practice is the substantially different distribution of primary cancer sites: cervical cancer accounted for 75% of the invasive genital cancers and 74% of deaths from genital cancer in ever-users, but only 31% of the invasive cancers and 30% of deaths in never-users.
Several lines of evidence indicate that cAMP modulates developmental gene activity via cell-surface receptors. We describe here a novel cAMP receptor, CABP1, whose properties are consistent with the idea that this protein is involved in gene regulation. Firstly, immunological techniques using anti-CABP1 antibodies as probes showed that this cAMP receptor can be detected on the surface of developing cells. Secondly, there is a steady migration of CABP1 to the nucleus during development. Thirdly, some genetic variants exhibiting an altered pattern of development are found to possess modified CABP1. We also showed that CABP1 co-purifies with at least seven other polypeptides which share common epitopes with CABP1. Interestingly, four of the CABP1-related polypeptides can be detected on the cell surface as well as in the nucleus.
1. Sodium and water reabsorption were determined in virgin controls and rats at 9 and 20 days of pregnancy during a water diuresis induced and maintained by infusion of 2.5% dextrose and in normally hydrated women during the third trimester and again 2-3 months after delivery. 2. Reabsorption from the proximal tubules and distal nephron segments was assessed using the clearance of lithium as a marker of the sodium and water delivery from the proximal tubules to the loops of Henle. 3. Glomerular filtration rate and whole-kidney reabsorption of sodium and water were significantly increased at both stages of pregnancy in rats and late in pregnancy in women when compared to the respective non-pregnant control. Fractional reabsorption was unaltered in pregnant rats but increased in pregnant women. 4. Proximal tubule sodium and water reabsorption were increased in pregnant rats and women; fractional reabsorption was unaltered. 5. Absolute reabsorption of sodium and water in distal nephron segments were increased during pregnancy in both rats and women. Although increases in fractional reabsorption were detected in pregnant women, this was not the case at either stage of gestation in rats.
Thyroid hormone, testosterone, and glucocorticoids stimulate the production of nerve growth factor (NGF) in mouse submandibular glands, but little is known about the influences of these hormones on other sources of NGF. In this study we tested the effects of thyroid hormone and steroids on NGF levels in medium conditioned by L-929 fibroblasts (L-cells), a mouse cell line that secretes NGF in culture. NGF concentrations in conditioned medium were measured by RIA and were normalized for cell number. In the absence of hormones, NGF levels in medium averaged 5.57 ng/ml. T3, cortisone, and aldosterone decreased NGF levels below the sensitivity of the RIA (less than 0.37 ng/ml), with respective ID50 values of 1 X 10(-5), 1 X 10(-8), and 5 X 10(-8) M. Testosterone decreased NGF levels by 66%, with an ID50 of 9 X 10(-9) M, and 17 beta-estradiol decreased it by up to 50%, although the hormone's effects had not plateaued at 10(-6) M. NGF concentrations were unaffected by progesterone at doses as high as 10(-6) M. Cell viability was unaffected by hormone treatment, and the total amount of secreted protein in medium decreased only in cultures treated with high doses of cortisone and aldosterone. Qualitatively similar results were obtained by bioassay; steroids markedly reduced, but did not eliminate, the nerve growth-promoting effects of L-cells on embryonic chick dorsal root ganglia in cocultures. These data indicate that hormones that stimulate NGF production in salivary glands inhibit NGF production by L-cells in culture.
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A method for the detection of specific IgE in human serum is described, using a modified radioimmune assay termed the Inhibition Assay Technique (IAT) The technique is based on the ability of specific IgE to bind with allergen. The difference in total IgE before incubation with the allergen and after incubation with the allergen gives a relative concentration of specific IgE to that particular allergenic substance. The assay has been shown to correlate with both the intradermal skin test as well as the standard RAST now used to determine specific IgE.
Using various concentration procedures (including the gauze pad method, ultrafiltration, and adsorption-elution), enteric viruses, mainly vaccine strains of polioviruses, were isolated from 61.8% of sewage, 20.5% of effluents, 3.0% of river water, and 6.7% of drinking water samples collected from a waterway system in Manitoba. The presence of polioviruses in the drinking water of the town utilizing this waterway was not correlated with an increase in the number of infectious diseases reported.
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The National Institute of Health Guidelines for Recombinant DNA Research recommends 2% aqueous Wescodyne, an iodophore that is used in many hospitals and laboratories as a disinfectant, as a decontaminant for biological safety cabinets and 5% for a spill outside a cabinet. A contact time of 10 to 15 minutes was given for the 2% solution and 20 minutes was considered adequate for the 5% concentration. The results indicate: 1. Aqueous Wescodyne (5%) is ineffective when used for 80 minutes against poliovirus in a test mixture containing 8.5% bovine serum albumin (a mixture equivalent in protein concentration to the higher range in serum). 2. Wescodyne (10%) employed under the same conditions for 40 minutes is also ineffective. 3. Wescodyne (10% v/v) in 50% ethanol (w/w) was effective and this mixture, originally recommended for hand washing, should be considered for use in biohazard situations, particularly for decontamination of work surfaces and biological safety cabinets. These results are of significance for if a virucide cannot inactivate poliovirus one would be concerned about using the virucide against hepatitis B or SV40 viruses.
We studied patients undergoing A-C Bypass with haemodilution. The bubble oxygenator was primed with either two units of plasma and lactated Ringer's solution (PLASMA) or with lactated Ringer's solution (RINGER'S) alone. We found no difference in pulmonary function or lung water determinations between the Ringer's and the Plasma groups. When all patients were grouped together we found no significant increase in lung water (ETVL)5 immediately post-operatively. This suggests lung water did not increase during cardiopulmonary bypass. By the following morning there was a highly significant increase in lung water which was related to changes in the balance between hydrostatic pressure and colloid osmotic pressure and which continued through the second post-operative day. Pulmonary dysfunction, as measured by gas exchange, was not a major problem except in one patient whose lung water increase exceeded 3 ml H2O/kg of total body weight (52 per cent increase) and in whom there was increased shunting. We consider the increase in lung water important, since it may reduce lung compliance and further lung water accumulation. Since the increased lung water was associated with a change in the balance of Starling's forces (PMV - COPMV), treatment designed to reduce that balance should reduce lung water accumulation.
The "General Health Questionnaire" was used to assess the psychiatric morbidity among 365 consecutive attenders at a general practice and to compare this with a systematic random sample of 213 patients drawn from the lists of the same practice. Those attending a general practitioner are shown to be more psychiatrically disturbed than a random sample of the practice population, and this difference remains when those attending for psychological symptoms are discounted. Various social and demographic characteristics which distinguish between those who do and those who do not attend a doctor with a given set of psychological symptoms are described.