PubMed Health⌕ Search

Biomedical subjects

S Greer

Publications and source records attributed to S Greer.

At least 73 records · Page 4Linked to original sources
PubMed1986

Sensitization to X ray by 5-chloro-2'-deoxycytidine co-administered with tetrahydrouridine in several mammalian cell lines and studies of 2'-chloro derivatives.

5-Chloro-2'-deoxycytidine (CldC) + tetrahydrouridine (H4U) sensitizes mammalian cells (HEp-2, RIF-1, S-180) to X ray. This sensitization, as demonstrated previously with HEp-2 cells, is heightened when cells are pre-incubated with inhibitors of pyrimidine synthesis. CHO cells, which intrinsically lack both cytidine deaminase (CD) and deoxycytidylate deaminase (dCMPD), are sensitized to X ray by 5-chlorodeoxyuridine (CldU) but display no significant sensitization with CldC + H4U. The presence and level of these deaminases appears to correlate with X ray sensitization in cell culture. From experiments in cell culture, it can be inferred that one pathway of conversion, deoxycytidine kinase----dCMPD, or CD----thymidine kinase, may be sufficient for metabolizing CldC to a radiosensitizer. However, if both pathways are blocked, as in CHO cells, no X ray sensitization results. In addition to HEp-2 cells, which are extremely elevated in both CD and dCMPD activities, we have examined the sensitization of S-180 and RIF-1 cells to X ray by CldC + H4U. Both cell lines possess an enzymatic profile consistent with their sensitization to X ray by CldC + H4U. Dose enhancement ratios of 1.5 to 1.9 for cells treated with CldC + H4U and ratios of 2.0-2.7 for cells pre-treated with inhibitors of pyrimidine synthesis prior to CldC + H4U have been obtained. Based on reports of the marked X ray sensitization of bacteria by 2'-chloro-2'-deoxythymidine, we obtained 2',5-dichloro-2'-deoxycytidine and 5-bromo-2'-chloro-2-deoxyuridine and found these analogs to be X ray sensitizers of mammalian cells. The strategy that we propose with CldC + H4U and the related 2'-chloro derivatives, based on the elevation of CD and dCMPD in human tumors, offers a degree of selectivity that is not necessarily related to differences in cell kinetics; such that malignancies other than brain tumors may be amenable to this therapy.

Animals↗
PubMed1986

Attitudes to psychiatry in doctors at the end of their first post-graduate year: two-year follow-up of a cohort of medical students.

The significantly favourable changes in medical students' general attitudes to psychiatry which we found after their 8-week clerkship in psychiatry and at the end of their clinical curriculum were not maintained at the end of their first post-graduate year. Three of their specific attitudes to psychiatry changed significantly in an unfavourable direction over this 2-year period. Our findings suggest that, while favourable changes in students' specific attitudes to psychiatry can be found following a clerkship, these attitudes do not seem to endure and, in some cases, they later become less favourable. The results are discussed with reference to the relationships between undergraduate medical training in psychiatry, attitudes to psychiatry, and subsequent career choice, particularly general practice.

Attitude of Health Personnel↗
PubMed1986

Responses of male and female physicians to medical complaints in male and female patients.

Workups by male and female physicians in response to five common complaints in a sample of 200 men and women-100 married couples-revealed no significant differences in the extent and content. This study contrasts with observations made in a previous study of male physicians who were found to perform more extensive workups for men than for women. The present study differs from the previous one in several respects, however: (1) the physicians are significantly younger, (2) the patients are significantly older, (3) the physicians practice in a prepaid health maintenance organization as opposed to a fee-for-service group, and (4) the practice consists of men and women partners. If the first and last factors are the most important in accounting for the present observations, it is possible that whatever sexist behavior exists will decline with the infusion of young physicians-both men and women-into the evolving medical practice setting.

Adult↗
PubMed1985

Towards a psychobiological model of cancer: psychological considerations.

To date, the evidence relating to the role of stress and psychological variables in cancer aetiology and promotion is contradictory. We have attempted to clarify the issues by presenting an hypothetical psychobiological model. Two components of this model are described: (1) a characteristic behaviour pattern (Type C) which may mediate stress reactions and (2) the biological concomitants of this behaviour pattern. The mechanisms of cancer initiation and promotion are described in a companion paper (Pettingale). The main hypothesis advanced by this model is that the psychological factors described may promote cancer development; the model is offered for investigation.

Emotions↗
PubMed1985

Referrals to psychiatrists in a general hospital--comparison of two methods of liaison psychiatry: preliminary communication.

Patients on a general medical ward were offered a liaison psychiatric service with 'unlimited' access, in which referrals were accepted from nurses, other paramedical staff and junior doctors in addition to senior medical staff. This new service (method II) was compared with the usual liaison service (method I, referrals initiated or approved by senior medical staff only) which was continued in parallel on a comparable general medical ward. Method II resulted in a threefold increase in referral rate and led to a significant alteration in the types of problem attracting referral. Despite the much higher rate of method II referrals, however, similar percentages of referrals by both methods were offered psychiatric follow up. The results do not support the commonly held belief that it is the failure of ward staff to recognize psychiatric morbidity which accounts for the low rate of referrals to many psychiatric liaison services.

Adult↗
PubMed1985

Metabolic channeling of 5-fluoro-2'-deoxycytidine utilizing inhibitors of its deamination in cell culture.

The metabolism of 5-fluoro-2'-deoxycytidine (FdC) with and without tetrahydrouridine (H4U) or 2'-deoxytetrahydrouridine (dH4U) was examined in log phase HEp-2 cells using HPLC and TLC methods which quantified: the incorporation of FdC-related antimetabolites into RNA and DNA and pool size levels of FdC-related antimetabolites. [3H]-FdC administered to log phase HEp-2 cells at a concentration of 0.01 microM for 24 hr resulted in the incorporation of 5.22 X 10(-8) mol of FdC/mol of DNA phosphate, a 0.021% substitution of FdC for dC. Coadministration of 1.0 mM H4U or dH4U resulted in 2- and 25-fold increases in the incorporation of FdC, respectively. No detectable incorporation of 5-fluoro-2'-deoxyuridine (FdU) into HEp-2 DNA resulted (detection limit, approximately 5 fmol). In contrast, treatment of HEp-2 cells with 0.1 microM FdU resulted in the incorporation of 1.83 X 10(-9) mol of FdU (74.7 fmol detected)/mol of DNA phosphate. A linear incorporation of FdC into the DNA of HEp-2 cells was found with increasing concentrations of FdC and 1.0 mM dH4U . 0.1 microM FdC resulted in the incorporation of 2.39 X 10(-6) mol of FUMP/mol of cytoplasmic RNA phosphate and 2.23 X 10(-5) mol of FUMP/mol of nuclear RNA phosphate. Similarly, HEp-2 cells treated with 0.1 microM FdU resulted in the incorporation of 1.10 X 10(-5) mol of FUMP/mol of nuclear RNA phosphate and 9.44 X 10(-7) mol of FUMP/mol of cytoplasmic RNA phosphate. In contrast, no detectable FUMP incorporation into either nuclear or cytoplasmic RNAs of HEp-2 cells resulted when H4U or dH4U was coadministered with 0.1 microM FdC. Pool size analyses of log phase HEp-2 cells following a 30-min exposure to FdU or FdC with and without H4U or dH4U were also performed; 0.1 microM FdC treatment resulted in the formation of 169 fmol of FUMP/1.0 X 10(6) viable HEp-2 cells. Treatment with 0.1 microM FdU produced 253 fmol of FUMP/1.0 X 10(6) viable HEp-2 cells. In contrast, no detectable FUMP pools were formed when H4U or dH4U was coadministered with 0.1 microM FdC (detection limit, approximately 5 fmol). Pool levels of FdUMP, the inhibitor of thymidylate synthetase, were also assayed; 36.9 fmol of FdUMP/1.0 X 10(6) viable HEp-2 cells were detected upon administration of 0.1 microM FdC.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

Comparison of radio-labeled DNA probe with a nonisotopic probe for assay of serum hepatitis B virus DNA.

A biotin-labeled DNA probe was compared to a 32P radio-labeled DNA probe for the detection of serum hepatitis B virus (HBV) DNA. Serum specimens were treated with proteolytic enzyme and detergent. DNA was extracted using phenol, denatured in sodium hydroxide and applied to a nitrocellulose filter paper using a vacuum filter device. The nitrocellulose filters were then incubated with either the biotin-labeled or the radio-labeled probe. Annealing of the probe, indicating the presence of HBV-DNA in the sample, was detected either by autoradiography for the 32P-labeled probe or by measuring the presence of an acid phosphatase attached to a streptavidin molecule for the biotin-labeled probe. Using the same 2-day time to complete the assays, excellent correlation of the qualitative and semiquantitative measurements were obtained using 20 HBsAg-positive and 9 HBsAg-negative sera. The nonisotopic assay detected 1.0 pg of HBV-DNA, a sensitivity comparable to reported sensitivities of 32P-labeled HBV-DNA probes when similar assay times are used. 0.02 pg/microliter of HBV-DNA was detected in a normal serum to which HBV-DNA in a recombinant plasmid was added. Our results indicate that the biotin-labeled HBV-DNA probe is approximately as sensitive as the radio-labeled probe for the detection of HBV-DNA using a similar assay time. Isotopic probe assays are more sensitive with longer assay times. The biotin-labeled probe offers the advantage of a longer shelf life and a nonisotopic assay procedure.

Acid Phosphatase↗
PubMed1984

Reaction to a diagnosis of breast cancer. Relationship between denial, delay and rates of psychological morbidity.

Psychological responses were measured in a newly diagnosed group of breast cancer patients during their hospital stay for primary surgical treatment by mastectomy. The aim was to assess the extent to which patients responded to the stress of a cancer diagnosis by denying the seriousness of the illness, and how this related to both level of distress and prior delay in seeking treatment. The data indicated that patients who denied the seriousness of a cancer diagnosis experienced significantly less mood disturbance during this period than those who were more accepting of the implications of this diagnosis. These findings suggest that a denial rather than a confrontation-coping-response may effectively reduce the short-term distress experienced during this initial period of hospitalization. Contrary to predictions, we failed to show an association between the length of delay in seeking treatment and denial of the diagnosis.

Anxiety↗
PubMed1984

Emotional control and autonomic arousal in breast cancer patients.

Thirty breast cancer patients and 27 "healthy" controls were compared for differences in personality, reported emotional state and autonomic responses occurring under conditions of acute experimental stress. The data indicated that breast cancer patients were more likely than a control group to report a tendency to control emotional reactions, particularly anger, and to respond to stress using a repressive coping style. Emotional state reported at different points throughout the procedure suggested that the breast cancer group experienced more anxiety and disturbance but were more inclined to inhibit their reactions. There were no differences between the groups on autonomic measures but within the breast cancer group increased electrodermal activity was significantly associated with a tendency to respond to stress using a repressive coping style. The results are discussed in relation to psychobiological models of cancer.

Adaptation, Psychological↗
PubMed1984

The psychological dimension in cancer treatment.

A cardinal principle of medical ethics, primum non nocere, is examined in relation to current cancer treatments. In randomised, clinical trials of such treatments, the quality of life of patients has been largely ignored. The few systematic psychological studies reported so far indicate the likelihood of considerable psychosocial morbidity associated with radical surgery and prolonging combined chemotherapy. Detailed measures of psychosocial adjustment should be included in all future clinical trials of cancer therapy in order: (i) to identify those patients who require psychological help and (ii) to enable clinicians to base their decisions regarding cancer therapy not only on the probability of prolonging or, in some cases, saving life, but also on an accurate knowledge of the quality of that life.

Breast Neoplasms↗
PubMed1984

The continuity of moral reform: community mental health centers.

Contemporary involvement of citizens in the formation of mental health policies continues a long history of influential lay advocates achieving desired reforms. The Community Mental Health Centers Program arose from, and also recognized, the citizens' movement for community care. This legislation mandated and encouraged citizen membership on the governing boards of local centers. The influence of these citizen bodies is seen in the diversity and continuing evolution of the local centers structurally, in orientation and in services provided. Three examples from original field research are provided to illustrate.

Community Mental Health Centers↗
PubMed1984

Marked radiosensitization of cells in culture to X ray by 5-chlorodeoxycytidine coadministered with tetrahydrouridine, and inhibitors of pyrimidine biosynthesis.

Our approach to overcome the problem of rapid catabolism and general toxicity encountered with 5-halogenated analogues of deoxyuridine (5-bromo, chloro or iododeoxyuridine), which has limited their use as tumor radiosensitizers, is to utilize 5-chlorodeoxycytidine (CldC) with tetrahydrouridine (H4U). We propose that CldC, coadministered with H4U, is metabolized in the following manner: CldC----CldCMP----CldUMP---- ----CldUTP----DNA. All the enzymes of this pathway are elevated in many human malignant tumors and in HEp-2 cells. In X irradiation studies with HEp-2 cells, limited to 1 or 2 radiation doses, we have obtained 3.0 to 3.8 apparent dose enhancement ratios (these represent upper limits) when cells are preincubated with inhibitors of pyrimidine biosynthesis: N-(Phosphonacetyl)-L-aspartate (PALA) and 5-fluorodeoxyuridine (FdU) or 5-fluorodeoxycytidine (FdC) + H4U. Optimum conditions for radiosensitization are: PALA (0.1 mg/ml) 18-20 hr prior to FdU (0.1 microM) or FdC (0.02 microM) + H4U (0.1 mM) followed 6 hr later by CldC (0.1-0.2 mM) + H4U (0.1 mM) for 56-68 hr. Viabilities of 10 +/- 4% to 15 +/- 1% (+/- S.E.) were obtained for drug-treated unirradiated cells. Enzymatic studies indicate that this toxicity may be tumor selective. CldC + H4U alone (at these concentrations) results in 20% substitution of CldU for thymidine in DNA (determined by HPLC analysis). Preliminary toxicity studies indicate that mice will tolerate treatment protocols involving a single dose of PALA (200 mg/kg) followed by a dose of FdU (50 mg/kg) and 3 cycles of CldC (500 mg/kg) + H4U (100 mg/kg) at 10 hour intervals, with marginal weight loss (4%). In this approach we seek to obtain preferential conversion of CldC to CldUTP at the tumor site by taking advantage of quantitative differences in enzyme levels between tumors and normal tissues.

Animals↗
PubMed1984

Use of 5-fluorodeoxycytidine and tetrahydrouridine to exploit high levels of deoxycytidylate deaminase in tumors to achieve DNA- and target-directed therapies.

In view of the 20- to 80-fold elevation of deoxycytidine-5'-phosphate (dCMP) deaminase in many human malignant tumors, we have utilized 5-fluorodeoxycytidine ( FdCyd ) coadministered with tetrahydrouridine ( H4Urd ) as a combination of antitumor agents against two murine solid tumors which possess high levels of dCMP deaminase. This approach is based on our past studies in which we demonstrated that FdCyd is an excellent substrate for mammalian 2'-deoxycytidine kinase, and that H4Urd increases the toxicity of FdCyd in the mouse. Cell culture studies utilizing 2'- deoxytetrahydrouridine which inhibits cytidine deaminase and as 2'- deoxytetrahydrouridine -5'-monophosphate inhibits dCMP deaminase, provide indirect evidence for the pathway that we had proposed in the past, 2'- Deoxytetrahydrouridine antagonized the toxicity of FdCyd to a greater extent than did H4Urd and showed marked antagonism in cytidine deaminase-deficient cells. Cell lines lacking both cytidine and 2'-deoxycytidine-5'-monophosphate deaminase were markedly resistant to FdCyd . Thymidine and deoxyuridine antagonized toxicity in a manner consistent with the proposed pathway of anabolism of FdCyd and consistent with its resulting in the inhibition of thymidylate synthetase. We have established the efficacy of FdCyd + H4Urd chemotherapy utilizing adenocarcinoma 755 and Lewis lung carcinoma in C57BL X DBA/2 F1 mice. An example of an optimum schedule versus Lewis lung carcinoma is FdCyd , 10 to 12 mg/kg, plus H4Urd , 25 mg/kg, coadministered simultaneously, once per day on Days 1 to 7 after tumor implantation. Tumor inhibitions on Days 12, 14, and 16 were 95, 90, and 80%, respectively, with 8% maximum weight loss. Comparative studies were undertaken only with Lewis lung carcinoma and it was established that FdCyd + H4Urd surpasses the efficacies of 5-fluorouracil and 5-fluorodeoxyuridine as well as FdCyd when administered without H4Urd . We propose that the administration of FdCyd with H4Urd can result in preferential, tumor-directed conversion of a nontoxic nucleoside analogue to a toxic antimetabolite by an enzyme that is markedly elevated in human tumor tissue. The analogues of deoxycytidine are resistant to catabolism and are anabolized by a different subset of enzymes than are 5-fluorouracil or 5-fluorodeoxyuridine; therefore, it is a novel approach. Not only are there intrinsic selectivity, metabolic stability, and the advantages that accrue from prodrug therapy in this strategy, but in addition, the potential for an exclusively DNA-directed effect exists. This is in contrast to approaches with 5-fluorouracil and 5-fluorodeoxyuridine, in which, in addition to DNA effects, parallel effe

Animals↗
PubMed1983

Development of a questionnaire measure of emotional control.

A questionnaire measure of emotional control was developed to evaluate the extent to which individuals report controlling anger, anxiety and depressed mood. Scale items were derived from responses to semi-structured clinical interviews with patients who were awaiting breast biopsy. Internal consistency and test-retest reliability data are reported, as well as correlations with the Marlowe-Crowne, the Spielberger State-Trait Personality Inventory, the Eysenck Personality Questionnaire and the Bortner Type A Behavior Scale. Although intended for use with breast cancer patients this scale is envisaged to have wider application to other clinical populations.

Adolescent↗
PubMed1983

Medical students' attitudes to psychiatry at the end of the clinical curriculum.

The significantly favourable changes in medical students' general attitude to psychiatry and intention to specialize in the subject, which we found after an 8-week psychiatric clerkship, were maintained one year later, at the time of the students' M.B., B.S. examinations. However, of 18 specific attitudes to psychiatry, only one changed significantly overall - fewer students agreed that 'psychiatrists are held in poor regard by most other doctors'. Contrary to other reports, these preliminary findings suggest that a psychiatric clerkship may be followed by stable attitudes and intent towards the specialty.

Attitude of Health Personnel↗
PubMed1983

Medical students' attitudes to psychiatry.

A questionnaire was developed to elicit medical students' attitudes to psychiatry. All 94 second year clinical students at a London teaching hospital completed the instrument before and after an 8-week psychiatric clerkship. Although two-thirds of the sample had mixed feelings about psychiatry initially, by the end of the clerkship the students' general attitude to psychiatry had changed significantly in a favourable direction. Analysis of 18 specific attitudes to psychiatry revealed that the students' first responses showed anticipatory bias and lack of uniformity. Later, however, only two specific attitudes had changed significantly: more students agreed that 'problems presented by psychiatric patients are often particularly interesting and challenging', and more of them disagreed with the statement that 'psychiatric patients, generally speaking, are not easy to like'. The sexes differed on one attitude; more males than females agreed that 'psychiatry is too inexact; it seems to lack a proper scientific basis'. Finally, the proportion of students who considered the possibility of specializing in psychiatry rose from 6 to 17% during the clerkship. The students' reasons for or against such a career are discussed.

Adult↗
PubMed1983

Incorporation of 5-substituted analogs of deoxycytidine into DNA of herpes simplex virus-infected or - transformed cells without deamination to the thymidine analog.

The incorporation into DNA of 5-bromocytosine and 5-iodocytosine, derived from their respective administered deoxyribonucleoside analogs, has been demonstrated in studies with cells infected with herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) and in cells transformed with the thymidine kinase gene of HSV-1. No significant incorporation of iodocytosine or iodouracil occurred in the DNA of uninfected or nontransformed cells when the deaminating enzymes were inhibited, in accord with past studies in our laboratory with 5-bromodeoxycytidine and tetrahydrouridine. When 2'-deoxytetrahydrouridine, a potent inhibitor of cytidine deaminase and dCMP deaminase, was utilized, all the counts in DNA that were derived from [(125)I]iododeoxycytidine appeared as iodocytosine in HSV-infected cells. In the absence of a deaminase inhibitor, 32 to 45% of the counts associated with DNA pyrimidines appeared as iodocytosine, and 55 to 68% appeared as iodouracil in HSV-infected cells. Substantial incorporation of iodocytosine (16%) occurred in cells transformed with the HSV thymidine kinase gene, suggesting the importance of the specificity of cellular nucleoside kinases and the activity of the deaminases in presenting unmodified bases to an undiscriminating polymerase. Incorporation into DNA of bromocytosine derived from [(3)H]bromodeoxycytidine was demonstrated in HSV-2 infected cells; very little incorporation of bromocytosine compared with bromouracil could be demonstrated in these cells in the absence of inhibition of the deaminases (19% of the total counts associated with pyrimidines with deaminase inhibition and 1.5% without). Limited studies with 5-methyl[5-(3)H]deoxycytidine indicated essentially no (or very little) incorporation of this analog as such in the DNA of HSV-1- and HSV-2-infected and -transformed cells. This suggests an exclusion or repair mechanism preventing inappropriate methylcytosine incorporation in DNA. The addition of nucleoside and deoxyribonucleoside deaminase inhibitors, which leads to the incorporation of 5-halogenated analogs of deoxycytidine into DNA as such, does not impair their antiviral activity. We infer from studies with 4-N-alkyl (ethyl and isopropyl)-substituted analogs of iododeoxycytidine that they are incorporated as such into DNA without deamination and effectively inhibit the virus at concentrations that are marginally toxic. Among the several reasons presented for the heightened potential efficacy of analogs of deoxycytidine compared with those of deoxyuridine is that the former, as analogs of 5-methyldeoxycytidine, may impair viral replication by perturbing processes involving methylation and changes in the methylation of deoxycytidine in DNA which appear to be important for the process of HSV maturation. In addition, this capacity to perturb methylation may, in turn, be the key to their potential as agents affecting entry into or emergence from latency, a process in which dramatic changes in the postpolymer 5-methylation of deoxycytidine occur in the DNA of herpesviruses.

Animals↗