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Biomedical subjects

A Cook

Publications and source records attributed to A Cook.

At least 145 records · Page 8Linked to original sources

A new anti-p53 monoclonal antibody, previously reported to be directed against the large T antigen of simian virus 40.

The PAb1620 antibody belongs to a group of monoclonal antibodies reported to recognize nuclear large T antigen of simian virus 40 (SV40). In the case of PAb1620 there was some indication that the antibody reacted preferentially with large T when it was complexed with p53, the cellular transformation-related antigen. However, we found that PAb1620 does not appear to react with SV40 large T, either free or in complex with p53. In this paper we demonstrate that PAb1620 is, in fact, directed against the p53 protein and recognizes a conformation-dependent epitope. In addition, PAb1620 recognises human p53 from SV80 cells.

Antibodies, Monoclonal↗

Evaluation of the nitrosamine hypothesis of gastric carcinogenesis in man.

Patients who had undergone a Billroth II gastrectomy (PG) or had pernicious anaemia (PA) and healthy matched control subjects (MC) participated in 24-h studies in which bacteria, nitrite and N-nitroso compounds (NOC) were measured in gastric juice and N-nitrosoproline (NPRO) in urine. Consistent with the nitrosamine hypothesis, intragastric levels of bacteria and nitrite were positively related to intragastric pH, but, contrary to the hypothesis, NOC in gastric juice and NPRO in urine were negatively related to intragastric pH.

Anemia, Pernicious↗

The cellular tumour antigen p53: evidence for transformation-related, immunological variants of p53.

The protein p53 is involved in the control of normal cell proliferation. However, when expressed abnormally, p53 also contributes to the process of cell transformation. The possibility that multifunctional forms of p53 exist was realised when two cell cycle dependent forms of the protein were identified in normal cells (lymphocytes: J. Milner, 1984, Nature (London) 310, 143-145). Interestingly these two forms of p53 in normal cells lack some of the epitopes recognised by monoclonal antibodies developed against p53 in transformed cells. This suggests that p53 may bear additional transformation-related epitopes in transformed cells. We have now investigated this possibility by screening a variety of cell lines for immunological variants of p53. The monoclonal antibodies PAb421, PAb122, RA3.2C2, PAb248, PAb200.47, and PAb246 were used. Our results indicate the existence of two immunologically distinct variants of p53 expressed in transformed cells. The two p53 variants are distinguished by the presence or absence of the epitope recognised by PAb246. A given cell line generally expressed a single immunological variant of p53. However, 3T6 cells expressed two subsets of p53 and appeared to modulate p53 synthesis in response to cell density.

Animals↗

Regional assignment of Y-linked DNA probes by deletion mapping and their homology with X-chromosome and autosomal sequences.

A series of Y recombinants have been isolated from Y-specific DNA libraries and regionally located on the Y chromosome using a Y deletion panel constructed from individuals carrying structural abnormalities of the Y chromosome. Of twenty recombinants examined twelve have been assigned to Yp and eight to Yq. Five of the Yp recombinants map between Yp11.2 and Ypter and one can only be assigned to Yp. Of the former, four detect homologies on the X chromosome between Xq13 and Xq24 and the latter one between Xp22.3 and Xpter. The sixth recombinant detects autosomal homologous sequences. The six remaining Yp probes are located between Ycen and Yp11.2. One of these detects a homology on the X chromosome at Xq13-Xq24 and a series of autosomal sequences, two detect uniquely Y-specific sequences and three a complex pattern of autosomal homologies. The remaining eight recombinants have been assigned to three intervals on Yq. Of three recombinants located between Ycen and Yq11.21 two detect only Y sequences and one additional autosomal homologies. Two recombinants lie in the interval Yq11.21-Yq11-22, one of which detects only Y sequences and the other an Xp homology between Xp22.3 and Xpter. Finally, the three remaining Yq recombinants all detect autosomal homologies and are located between Yq11.22 and Yq12. The divergence between homologies on different chromosomes has been examined for three recombinants by washing Southern Blots at different levels of stringency. Additionally, Southern analysis of DNA from flow sorted chromosomes has been used to identify autosomes carrying homologies to two of the Y recombinants.

Chromosome Deletion↗

Visualisation, by immunocytochemistry, of p53 at the plasma membrane of both nontransformed and SV40-transformed cells.

The cellular protein p53 normally functions in the control of cell proliferation; but, when expressed abnormally p53 also contributes towards the process of cell transformation. The functioning of p53 is thought to involve interaction with specific cellular targets and, in SV40- and other transformed cells, p53 is located in the nucleus: thus p53 may function via interacting with specific nuclear components. In addition, there is indirect evidence that in SV40-transformed cells p53 is also associated with the plasma membrane; however, this is not evident in cells stained by immunofluorescence. We have sought to obtain direct evidence for p53 at the plasma membrane by staining with a very sensitive immunocytochemical procedure. We have compared SV40-transformed BALB 3T3 cells with BALB 3T3, NIH 3T3, and NIH 3T3 transfected with v-mos provirus. The last cell line is tumorogenic. We found direct evidence for p53 at the plasma membrane for each cell line. In nontransformed and SV40-transformed cells the association of p53 with the plasma membrane was restricted to the period of mitosis. These results indicate that association of p53 with the plasma membrane is a normal, rather than a transformation-related phenomenon, and is temporally linked to the period of mitosis.

Animals↗

Pharmacokinetics and pharmacodynamics of intravenous midazolam in patients with severe alcoholic cirrhosis.

Midazolam kinetics and psychomotor function were studied after an intravenous dose of 0.075 mg/kg body weight in seven patients with alcoholic cirrhosis and eight control patients. Four of the seven cirrhotics died of complications of their liver disease within six months of the study. The metabolism of midazolam was significantly impaired in the cirrhotic patients (p less than 0.025). These patients also had evidence of greater sedation than the control group for up to six hours after the dose was administered (p less than 0.05). The clearance of midazolam did not correlate significantly with the serum albumin, or bilirubin, or with the kinetics of antipyrine, or indocyanine green. This study shows significant delay in the elimination of midazolam and decreased psychomotor function in patients with severe alcoholic liver disease. Caution is needed in using this drug for premedication in such patients before endoscopy.

Adult↗

Hormones, mood and sexuality in lactating women.

Of 25 primiparous women, investigated prospectively for six months post-partum, 19 persisted with breast feeding and six changed to artificial during the first six weeks. Sexual activity, mood, and feeding patterns were recorded in weekly diaries. Hormones were measured from weekly urine samples (oestrogen and pregnanediol) and fortnightly blood samples (prolactin, testosterone, androstenedione, and sex hormone binding globulin). In breast-feeding women, testosterone and androstenedione levels were significantly lower in those who reported severe reduction in sexual interest. Changes in sexuality or mood were not related to levels of prolactin or oestrogen, or to the return of follicular activity, which was delayed in persistent breast feeders. The relationships of mood, sexuality, and hormones are discussed.

Adult↗

pH profile of the adsorption of nucleotides onto montmorillonite. I. Selected homoionic clays.

The effect of adsorbed ions and pH on the adsorption of several purine and pyrimidine nucleotides on montmorillonite was studied. The cations used to prepare homoionic montmorillonite was Na+, Mn2+, Fe3+, Co2+, Ni+, Cu2+, and Zn2+. The nucleotides studied were 5'-,3'-, and 2'-AMP, and 5'-CMP in the pH range 2 through 12. The results show that preferential adsorption amongst nucleotides and similar molecules is dependent upon pH and the nature of the substituted metal cation in the clay. At neutral pH, it was observed that 5'-AMP was more strongly adsorbed than 2'AMP, 3'-AMP, and 5'-CMP. Cu2+ and Zn2+ clays showed enhanced adsorption of 5'-AMP compared to the other cation clays studied in the pH range 4-8. Below pH 4, the adsorption is attributed to cation and anion exchange adsorption mechanisms: above pH 4, anion exchange may also occur, but the adsorption (when it occurs) likely depends on a complexation mechanism occurring between metal cation in the clay exchange site the biomolecule. It is thus proposed that homoionic clays may have played a significant role in the concentration mechanism of biomonomers in the prebiotic environment, a prerequisite step necessary for the formation of biopolymers in the remaining steps leading to the origin of life.

Adenosine Monophosphate↗

Is delayed treatment justified in carcinoma of the prostate?

We report a retrospective survey of 263 patients with prostate cancer presenting between 1975 and 1979, with a minimum follow-up period of 5 years. We have evaluated the effects of anti-cancer therapy on survival and disease-free interval. The mean survival time of all patients was 39.6 months. Of 91 patients (37.7%) with demonstrable bone metastases at presentation, 64 (70.3%) have died of prostatic cancer, the mean duration of survival being 25 months. There was no difference in terms of response to treatment or of duration of symptom-free life between patients treated by immediate hormone manipulation and those in whom treatment was delayed. Of 115 patients without metastases at presentation, 42 (36.5%) received no anti-cancer treatment. Thirty-seven (32.2%) have died of unrelated causes and 39 (33.9%) are alive and well. Neither survival nor subjective response to treatment was adversely affected by delaying treatment.

Bone Neoplasms↗

Appraising your suture distribution system.

Devoting study to a minute part of its supply system has paid off in big dividends for Hutchison Hospital, an acute care hospital in central Kansas with 230 beds and an occupancy rate of 71%. In this article the author explains why other hospitals may find it profitable to take a close look at their suture distribution systems.

Equipment and Supplies, Hospital↗

Traditional treatment of colon injuries. An effective method.

Several recent reports have described management of penetrating colon wounds with primary closure, exteriorization, and early return to the abdominal cavity. Since this procedure was not the technique practiced at our institution, we reviewed our five-year experience with 207 patients with such wounds to determine whether a change in methods was warranted. The patients, predominantly young and male, were often victims of gunshots or stabbings. Associated injuries (intra-abdominal, 64%; extra-abdominal, 35%) were frequent. Overall mortality was 4% and included three patients who died within 24 hours of admission. Morbidity was 43%, including 17% related to colon injury. All documented colostomy closures were without mortality. We concluded that management of penetrating colon injuries by traditional methods yields low morbidity and mortality. A comparison of our results with those obtained using alternative techniques convinced us that the continued use of traditional methods in treating colon trauma is warranted.

Adolescent↗

Structural and biochemical differentiation of the mammalian small intestine during foetal development.

Microscopical studies showed that initial differentiation of the guinea-pig small intestine occurs between days 35 and 55 of foetal development. Changes observed at this time include formation of villi (by day 42), elaboration of submucosal duodenal Brunner's glands (by day 49) and the appearance of a well-developed microvillus membrane (by day 56). Different microvillus membrane-associated hydrolases appear at different stages of foetal and postnatal development. The 'early' enzymes such as aminopeptidase, alkaline phosphatase and sucrase show a sharp increase and reach their maximal levels between days 35 and 50, whereas the late enzymes such as dipeptidyl peptidase IV and lactase increase gradually between days 35 and 50, and reach maximal activity between days 50 and 60. A combination of techniques involving precipitation with Mg2+ followed by fractionation on sucrose density gradients has enabled us to prepare, for the first time, a 21-fold enriched microvillus membrane fraction from the foetal intestine. Polypeptide analysis of this membrane fraction by sodium dodecyl sulphate/polyacrylamide gel electrophoresis showed the presence of developmentally specific polypeptides at different stages of foetal and postnatal development. Three polypeptides of molecular weights 205 000, 80 000 and 47 000 are major microvillus membrane components at the 40-day foetal stage. Two other polypeptides of molecular weights 60 000 and 131 000 are major microvillar components at 56-day and older foetal stages as well as at the 3-day neonatal stage. The adult microvillus membrane contained 112 000 and 122 000 Mr polypeptides as major components. The above results were confirmed using two-dimensional isoelectric focussing-sodium dodecyl sulphate/polyacrylamide gel electrophoretic techniques.

Animals↗

Fertility after childbirth: pregnancy associated with breast feeding.

During studies on the resumption of fertility postpartum in 12 breast feeding mothers who were using no contraception, eight pregnancies occurred. In seven cases these pregnancies occurred while the mothers continued to breast feed while in one it occurred within 2 weeks of weaning. In two cases pregnancy occurred prior to first postpartum menstruation but followed an abrupt decline in suckling frequency and duration resulting in resumption of follicular development and ovulation. In the remaining six cases, pregnancy was preceded by between 1 and 7 menstrual cycles, the majority of which (13/19) had deficient luteal phases or were anovular (4/19). In all mothers a significant decrease in the suckling frequency and duration observed during lactational amenorrhoea had occurred prior to the resumption of ovulation and conception. No mother conceived with a suckling frequency of greater than three times per day although some mothers ovulated without conceiving when suckling four times per day. The results suggests that if a breast feeding mother wishes to rely upon the infertility associated with lactational amenorrhoea, she must suckle at least five times per day with a total suckling duration of more than 65 min per day (more than 10 min per feed). Any reduction below either of these limits may result in a return of fertility.

Adult↗