Nursing and health care in Israel.
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Delivery of Health Care↗
Biomedical subjects
S McMillan
Publications and source records attributed to S McMillan.
Chemical synthesis of idiotopes. Evidence that antisera to the same JH1 peptide detect multiple binding site-associated idiotopes.
In an attempt to better understand the molecular basis of idiotypy, we have generated several site-specific antisera through immunization of animals with synthetic peptides corresponding to the (JH1) heavy chain joining segment 1 of the mouse heavy chain variable (VH) region. These anti-peptide sera identify several idiotypic determinants present on intact hybridoma and myeloma immunoglobulins. Expression of at least three of these idiotopes is correlated with the antigen specificity of the family of immunoglobulins bearing the determinant. Use of synthetic peptides may prove a powerful technique in the generation of molecularly defined antiidiotypic reagents.
Amino Acid Sequence↗
Synthetic idiotypes: the third hypervariable region of murine anti-dextran antibodies.
Synthetic peptides with the sequence of the third hypervariable region of either M104 or J558 murine myeloma proteins have been used to immunize rabbits. Most of the resulting antisera distinguished the two proteins in a specific manner corresponding to the sequence of the immunizing peptide. Thus synthetic peptides have been used to elicit antisera specific for particular idiotypes. These studies have significant implications for our understanding of the molecular basis of idiotypy.
Animals↗
Relative sensitivity of V79 and V79/79 cells to spontaneous and induced mutation to 6-thioguanine and ouabain resistance.
The relative responses of V79 and V79/79 cells to mutation to 6-thioguanine (6TGR) and ouabain resistance (OUAR) have been compared in unmutagenized cells and after exposure to ethyl methanesulphonate (EMS), N-methyl-N-nitrosourea (MNU) and ultraviolet light. In the V79/79 cell line, the spontaneous frequency of 6TGR colonies but not of OUAR colonies was enhanced compared to that in V79 cells. This appears to be the result of a reduced growth rate and plating efficiency of V79/79 cells and does not reflect a real difference in spontaneous mutability. V79/79 cells were more sensitive than V79 to the cytotoxic effects of all three mutagens, but induced mutation by UV, EMS and MNU to 6TGR was similar in the two cell lines. The lack of a differential response for induced mutation to 6TGR may reflect: (a) differences in selective stringency of thioguanine in the two cell lines, and (b) the greater susceptibility of V79/79 cells to induced chromosome damage. The relative mutability of the two cell lines to OUAR was dependent on the mutagen used. V79 cells were significantly more mutable than V79/79 cells after MNU exposure, but the two cell lines were similar in sensitivity to EMS-induced mutation. After UV-irradiation, however, V79/79 cells were morem utable than V79 cells. The differential response of the two cell lines to MNU suggests that O6-methylguanine is potentially mutagenic in V79 cells but is both potentially lethal and potentially mutagenic in the more sensitive V79/79 cells. The absence of a differential response to EMS-induced mutagenesis suggests that methylated and ethylated bases are repaired differently in Chinese hamster cells. The hypermutability of V79/79 cells by UV-irradiation indicates that thymine dimers are potentially lethal and potentially mutagenic in both cell lines.
Animals↗
The repair of DNA damage: recent developments and new insights.
This brief review presents the salient features of new developments in the enzymatic repair of base damage to DNA. DNA glycosylases and apurinic/apyrimidinic (AP) endonucleases are reviewed and evidence is presented that in at least two prokaryote systems incision of UV-irradiated DNA occurs by the sequential action of these two classes of enzymes. In contradistinction, the uvrA, uvrB, and uvrC gene products of E coli appear to function as a multi-protein complex that catalyzes hydrolysis of phosphodiester bonds in damaged DNA directly. The inducible rapid repair of O6-methylguanine in E coli is also reviewed.
DNA↗
Effects of metabolic inhibitors on cell lethality and mutation induction in Chinese hamster cells. I. Inhibitors of de novo purine synthesis and a comparison with the effects of caffeine.
The effect of pre- and posttreatment incubation of UV-irradiated and ethyl methanesulphonate (EMS) treated cells with non-toxic concentrations of inhibitors of de novo purine synthesis (dnPS) on expression of potentially lethal and premutational damage at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus in V79 cells has been examined. The concentrations of inhibitors used were shown to profoundly perturb de novo DNA synthesis, by measurements of [14C]formate uptake, and cell cycle progression by flow cytofluorimetry. Postincubation in 6-methyl mercapto-purine ribonucleoside (MMPR) usually but not invariably potentiated the cytotoxic effect of UV and EMS but azaserine (AZS) and methotrexate (MTX) were without effect. No effects on mutant frequencies were observed on posttreatment with any of these agents. Caffeine produced the least effect on dnPS, but invariably potentiated lethal damage. This potentiation of lethal damage is not mediated by dnPS inhibition as has been suggested for Chinese hamster ovary (CHO) cells.
Animals↗
Effects of metabolic inhibitors on cel lethality and mutation induction in Chinese hamster cells. II. The effect of posttreatment with non-toxic concentrations of thymidine.
The ability of posttreatment exposure to non-toxic concentrations of thymidine (TdR) to enhance the lethal effects of a number of alkylating agents, X-rays and UV and the lethal and mutagenic effects of N'-ethyl-N-nitrosourea (ENU) and N-methyl-N-nitrosourea (MNU) has been examined in V79 cell lines. TdR posttreatment enhanced the cytotoxic effects of ethyl methanesulphonate (EMS), MNU and ENU but not of UV or X-rays and increased both the spontaneous and MNU- and ENU-induced frequencies of azaguanine resistant (AZR) mutants. No significant effect of TdR on the spontaneous frequency of thioguanine resistant (TGR) mutants was demonstrated but the frequency of MNU-induced mutants to TGR premutagenic was enhanced. The effects on expression of both potentially lethal and premutagenic damage were reversed by addition of an equimolar concentration of deoxycytidine (dCdR). The enhancement in spontaneous and induced mutant frequency (IMF) at the HGPRT locus appears to be due to an alteration in the selective efficiency of urine analogous due to alteration in growth kinetics of cells exposed to TdR or treated with alkylated agents or posttreated with thymidine after alkylation damage and not to an alteration in the miscoding potential of alkylated bases.
Animals↗
den V gene of bacteriophage T4 codes for both pyrimidine dimer-DNA glycosylase and apyrimidinic endonuclease activities.
Recent studies have shown purified preparations of phage T4 UV DNA-incising activity (T4 UV endonuclease or endonuclease V of phage T4) contain a pyrimidine dimer-DNA glycosylase activity that catalyzes hydrolysis of the 5' glycosyl bond of dimerized pyrimidines in UV-irradiated DNA. Such enzyme preparations have also been shown to catalyze the hydrolysis of phosphodiester bonds in UV-irradiated DNA at a neutral pH, presumably reflecting the action of an apurinic/apyrimidinic endonuclease at the apyrimidinic sites created by the pyrimidine dimer-DNA glycosylase. In this study we found that preparations of T4 UV DNA-incising activity contained apurinic/apyrimidinic endonuclease activity that nicked depurinated form I simian virus 40 DNA. Apurinic/apyrimidinic endonuclease activity was also found in extracts of Escherichia coli infected with T4 denV+ phage. Extracts of cells infected with T4 denV mutants contained significantly lower levels of apurinic/apyrimidinic endonuclease activity; these levels were no greater than the levels present in extracts of uninfected cells. Furthermore, the addition of DNA containing apurinic or apyrimidinic sites to reactions containing UV-irradiated DNA and T4 enzyme resulted in competition for pyrimidine dimer-DNA glycosylase activity against the UV-irradiated DNA. On the basis of these results, we concluded that apurinic/apyrimidinic endonuclease activity is encoded by the denV gene of phage T4, the same gene that codes for pyrimidine dimer-DNA glycosylase activity.
DNA Glycosylases↗
Relative mutagenicity of antineoplastic drugs and other alkylating agents in V79 Chinese hamster cells, independence of cytotoxic and mutagenic responses.
The mutagenic and cytotoxic effects of 4 antineoplastic drugs, vinblastine, vincristine, adriamycin and nitrogen mustard and of several monofunctional alkylating agents have been assayed in V79 Chinese hamster cells. Vincristine, vinblastine and nitrogen mustard did not significantly increase the frequency of TGRHGPRT- mutants but were were all highly cytotoxic. Adriamycin and the monofunctional alkylating agents were all significantly mutagenic even at the lowest doses tested (approx. 70% survival level). Induced mutant frequency increased linearly with increasing dose whereas dose-response curves for cytotoxicity for these effective mutagens invariably showed a shoulder followed by an exponential decline. At equitoxic doses the relative mutagenic effectiveness was MNU > ENU > EMS > MNNG > MMS greater than or equal to DMS. MNU was approx. 20 times more effective than MMS and DMS. Measurement of the total amount of alkylation and the relative amounts of reaction with individual DNA bases at approx. equitoxic doses of MNU and DMS indicated a significantly higher O6/N7 ratio after MNU (0.15) than after DMS (0.005). However, approx. equal numbers of mutants/10(5) cells/microM O6-Meguanine were induced by these 2 agents. These results support previous conclusions, that mutagenic and cytotoxic responses are independent in V79 cells.
Alkanesulfonates↗
Failure of caffeine to influence induced mutation frequencies and the independence of cell killing and mutation induction in V79 Chinese hamster cells.
Using V79 Chinese hamster cells and a replating assay, no effect of caffeine post-treatment on spontaneous or UV- or EMS-induced mutation frequencies to 8-azaguanine resistance was demonstrable. However, considerable potentiation of cell killing was observed. Previous reports that caffeine enhances induced mutation frequencies are explained by an artefact in the situ method used; a similar artefact may also explain the cumulative in situ mutation dose-response curves. Furthermore, the relationship between mutation induction and dose has been shown to be qualitatively distinct from that between cell killing and dose. These differences suggest that cell killing and mutation induction are mediated via independent mechanisms and that pre-mutational lesions may be qualitatively distinct from pre-lethal lesions.
Animals↗
Value of electrocardiogram in predicting and estimating infarct size in man.
The value of the electrocardiogram in assessing infarct size was studied using serial estimates of the MB isomer of creatine kinase (CK MB) in plasma, serial 35 lead praecordial maps in 28 patients with anterior myocardial infarction, and serial 12 lead electrocardiograms in 17 patients with inferior myocardial infarction. In patients with anterior infarcts, sigma ST, sigma R, sigma Q, sigma R/(Q+S), and the number of sites with ST elevation more than 2 mm or with QS waves, were obtained from each map. Correlation between both maximum sigma Q and maximum sigma ST with cumulative CK MB was highly significant. There was also a significant correlation between sigma R and sigma R/(Q+S) with cumulative CK MB. There was no significant correlation between maximum number of sites with ST elevation or with Q or QS waves and cumulative CK MB. Maximum sigma ST and number of sites with ST elevation predicted maximum sigma Q and number of sites with QS or Q waves at a time when infarction was not complete. In patients with inferior infarcts, there was a significant correlation between maximum sigma Q and maximum sigma ST in leads II, III, and a VF, and cumulative CK MB. This study shows that all the waves in the electrocardiogram are useful in assessing infarct size. The fact that maximum sigma ST predicts final sigma Q may be used to assess the efficacy of interventions designed to salvage ischaemic myocardium.
Aged↗
Diazepam, alcohol and drivers.
Fifteen hundred drivers' blood samples have been analysed for the drug diazepam (Valium) over a three-year period. Of 1000 hospitalised drivers whose blood samples were forwarded to DSIR for alcohol analysis, diazepam was detected in 2.0% and alcohol in over 90%. Diazepam was found to a lesser extent in blood samples from 370 fatally injured drivers, and from 130 apprehended drivers who returned low blood alcohol levels. The significance of the levels of diazepam and its major metabolite in blood are discussed in relation to the blood alcohol level and consequent driving impairment.
Accidents, Traffic↗
Sporotrichoid leishmaniasis.
American leishmaniasis that is acquired in Panama may appear clinically as a sporotrichoid eruption. When leisons reminiscent of sporotrichosis are encountered, a careful history of the patient's travels should be made, as well as a search for the organism of leischmaniasis in tissue smears, histopathological sections, and cultured media. We report the case of an American soldier stationed in Panama who had developed an ulcer on the dorsum of his right wrist, and nodules on his right forearm that were arranged in a linear pattern. The initial clinical impression was that of sporotrichosis, but on careful study of the patient's history, and after other appropriate investigations were made, it was discovered that the patient had leishmaniasis.
Adult↗
Pyrimidine dimer-DNA glycosylases: studies on bacteriophage T4-infected and on uninfected Escherichia coli.
Pyrimidine dimer (PD)-DNA glycosylase activity has been reported in both the M. luteus and phage T4 UV endonucleases. In the present studies the T4 PD-DNA glycosylase has been purified close to physical homogeneity using an assay that measures the release of free thymine from UV-irradiated poly ([H5] dT):poly (dA), after the photo-reversal of thymine-thymine dimers. The activity has also been demonstrated in vivo following infection of UV-irradiated E. coli uvr- cells with phage T4. Under these conditions the T4 PD-DNA glycosylase accounts quantitatively for all thymine-containing PD excised from [3H] labeled E. coli DNA. In vitro the T4 PD-DNA glycosylase has an associated AP endonuclease activity that incises UV-irradiated DNA 3 to the apyrimidinic sites created by the glycosylase. However, the glycosylase/AP endonuclease reaction mechanism in vitro does not appear to be a concerted one. In addition, a T4 phage with a temperature-sensitive mutation in the denV gene shows wild-type levels of survival at the permissive temperature, despite the fact that in vitro, extracts of E. coli infected with this mutant show no detectable phage-coded AP endonuclease at 28 degrees C. Thus the exact role of the T4 AP endonuclease in the incision of UV-irradiated DNA dimer in vivo is not clear. The ratio of excised non-containing nucleotides to dimer-containing nucleotides following infection of UV-irradiated E. coli with phage T4 denV+ yields a calculated average repair patch size of approximately 7 nucleotides. In contrast, the calculated average patch size in uninfected E. coli is approximately 70 nucleotides. Thus the extent of excision/resynthesis of UV-irradiated DNA may be determined by the specific mode of incision of the DNA at PD. When uninfected E. coli (uvr+) is exposed to UV radiation, a fraction of the excised thymine-containing PD contain photolabile thymine, suggesting the presence of PD-DNA glycosylase in E. coli. The role of this putative activity in the metabolism of UV-irradiated DNA is under investigation.
DNA Glycosylases↗
A synthetic peptide induces a new anti-dextran idiotype.
We have synthesized the JH1 peptide and coupled it to keyhole limpet haemocyanin for use as an immunogen. A serum from an animal hyperimmunized with this immunogen demonstrated binding to both peptide and native immunoglobulin. Furthermore, this serum seems to define an idiotypic determinant nearly unique to alpha (1 ---- 3) dextran-binding immunoglobulins. Synthetic peptide immunogens may be a useful tool in probing the molecular basis of idiotypy.
Amino Acid Sequence↗
Survey of graduate programs in cancer nursing.
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Directories as Topic↗
Validity and reliability of medical and surgical oncology patient acuity tools.
PURPOSE/OBJECTIVES: To develop valid and reliable medical and surgical acuity tools as part of an overall classification system for patients with cancer. SETTING: An acute care, tertiary, research, academic oncology hospital in the southeastern United States. SAMPLE: Clinical nursing experts in medical and surgical oncology; 125 patient observations for the surgical oncology acuity tool, and 75 patient observations for the medical oncology acuity tool. METHOD: The nursing division developed a medical oncology acuity tool and a surgical oncology acuity tool using the Johns Hopkins Oncology Patient Classification System as a model. They then studied the validity of developed tools using content validity indexes (CVIs). Two independent raters studied the interrater reliability of each tool. FINDINGS: CVIs for items on the surgical tool ranged from 0.57-1.0; the overall CVI for this tool was 0.86. CVIs for items on the medical tool ranged from 0.25-1.0. The overall CVI for this tool was 0.88. Pearson correlation coefficients were r = 0.95 (p < 0.001) for the surgical oncology acuity tool and r = 0.92 (p < 0.001) for the medical tool. Interrater reliability, tested continually for four years, was greater than 95%. CONCLUSIONS: The tools are reliable and valid. IMPLICATIONS FOR NURSING PRACTICE: Medical and surgical oncology acuity tools that are nursing diagnosis based, interface with nursing standards of care, are easy to use, and require no calculation provide reliable quantification of nursing work loads based on the care needs of patients with cancer. Supervisors use data from these tools to determine variable nursing hours per patient per day, establish productivity for units, make staffing and scheduling decisions, assign patients, work on budgets, and, ultimately, establish charges for nursing services. As the needs of medical and surgical oncology patients evolve, continued refinement of indicators and acuity levels will be needed. As other medical and surgical oncology tools are developed, further comparison will be warranted. Additional study would determine if the tools could be modified for these nursing uses in other cancer centers as well as in designated medical and surgical oncology units of other types of hospitals. Oncology acuity systems also could be established in the future as the basis for third-party reimbursement.
Cancer Care Facilities↗
Study reveals isolation and strain in HIV/AIDS workers.
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HIV Infections↗