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Biomedical subjects

S G Martin

Publications and source records attributed to S G Martin.

18 recordsLinked to original sources
PubMed1998

Mutation of yeast Ku genes disrupts the subnuclear organization of telomeres.

The mammalian Ku70 and Ku86 proteins form a heterodimer that binds to the ends of double-stranded DNA in vitro and is required for repair of radiation-induced strand breaks and V(D)J recombination [1,2]. Deletion of the Saccharomyces cerevisiae genes HDF1 and HDF2--encoding yKu70p and yKu80p, respectively--enhances radiation sensitivity in a rad52 background [3,4]. In addition to repair defects, the length of the TG-rich repeat on yeast telomere ends shortens dramatically [5,6]. We have shown previously that in yeast interphase nuclei, telomeres are clustered in a limited number of foci near the nuclear periphery [7], but the elements that mediate this localization remained unknown. We report here that deletion of the genes encoding yKu70p or its partner yKu80p altered the positioning of telomeric DNA in the yeast nucleus. These are the first mutants shown to affect the subnuclear localization of telomeres. Strains deficient for either yKu70p or yKu80p lost telomeric silencing, although they maintained repression at the silent mating-type loci. In addition, the telomere-associated silencing factors Sir3p and Sir4p and the TG-repeat-binding protein Rap1p lost their punctate pattern of staining and became dispersed throughout the nucleoplasm. Our results implicate the yeast Ku proteins directly in aspects of telomere organization, which in turn affects the repression of telomere-proximal genes.

Animals↗
PubMed1998

Analysis of complement receptor type 1 (CR1) expression on erythrocytes and of CR1 allelic markers in Caucasian and African American populations.

CR1 expression on erythrocytes (E) is regulated by an element that is tightly linked in Caucasians to the site of an RFLP of the CR1 gene. Genomic HindIII fragments of 7.4 and 6.9 kb identify alleles that are expressed in high (H allele) or low (L allele) amounts, respectively. When age-fractionated E of donors heterozygous for both the H and L alleles and for CR1 allotypes of differing molecular weights were analyzed in Western blots, the product of the L allele appeared to have an increased rate of loss during cell aging. A coding sequence polymorphism of CR1 predicted to cause a Pro-->Arg substitution in its proximal extramembranous region was tightly linked in Caucasians to the site of the HindIII RFLP. However, neither this polymorphism nor the HindIII RFLP correlated with CR1 expression among African Americans. Relative instability of CR1 encoded by the L allele thus may derive from another coding sequence polymorphism, or may require both the Pro-->Arg substitution and epistatic effects of another polymorphic gene.

Alleles↗
PubMed1995

Photoneutrons from medical linear accelerators--radiobiological measurements and risk estimates.

PURPOSE: To assess the oncogenic potential of the photoneutrons produced by high energy medical linear accelerators. METHODS AND MATERIALS: An established line of cells of rodent origin (C3H 10T1/2) was used to assess the oncogenic potential of the radiation dose received in the breast of an anthropomorphic "randoman" phanton, while the cervix received a dose of 70 Gy. Experiments were performed at 6 MV, below the threshold for the production of photoneutrons, and at 20 MV where the dose includes about 0.01 Gy of photoneutrons as well as scattered x-rays. RESULTS: A significantly higher transformation incidence was observed for the 20-MV machine, consistent with the measured neutron dose of about 0.01 Gy and a quality factor of 20. CONCLUSION: An estimate can be made of the additional deaths from second malignancies that might result from the photoneutrons generated by higher energy linear accelerators (Linacs), which must be offset against the possible improvements in survival that might result from the higher tumor doses made possible by the increased percentage depth doses.

Animals↗
PubMed1995

Neutron-induced cell cycle-dependent oncogenic transformation of C3H 10T1/2 cells.

Exposure of synchronized populations of mouse C3H 10T1/2 cells to a single dose (0.6 Gy) of 5.9 MeV neutrons at intervals after mitotic shake-off results in a distinctive variation in the oncogenic transformation frequency through the cell cycle. Previous findings show a sensitive window for X-ray-induced oncogenic transformants at late times after mitotic shake-off (14-16 h). Optimal sensitivity to neutrons was observed for cell populations irradiated soon after mitotic shake-off (4-6 h), where the majority of cells would be in the G1 phase of the cell cycle. Additionally, enhanced sensitivity was also found for that period after shake-off (14-16 h) which was maximally sensitive to X rays corresponding to cell populations with a high proportion of G2-phase cells. That is, low-LET radiation (250 kVp X rays) largely appears to produce oncogenic transformants in G2-phase cells, while intermediate-LET radiation (5.9 MeV neutrons) is effective principally on G1- and, to a somewhat lesser extent, G2-phase cells. Cells irradiated with neutrons showed less variation for lethality through the cell cycle than those irradiated with X rays, in agreement with previous findings. The mechanistic basis for the difference in the response of cells in the different phases of the cell cycle to radiations of different quality is unknown but is suggestive of distinct ("signature") molecular changes leading to the observed oncogenic transformation response.

3T3 Cells↗
PubMed1995

The biological effectiveness of radon-progeny alpha particles. II. Oncogenic transformation as a function of linear energy transfer.

Epidemiological studies have established an association between exposure to radon and carcinoma of the lung. However, based on data for either lung cancer in uranium miners exposed to radon or bronchial epithelial carcinomas in Japanese A-bomb survivors, it has not been possible to assign estimates of risk of lung cancer for the general population exposed to radon in their homes. Based on past success with the excellent quantitative properties of the C3H 10T1/2 in vitro oncogenic transformation assay system, the relative biological effectiveness (RBE) for radiation-induced transformation for charged particles of defined LET has been determined. As the LET of the radiation was increased, the rate of induction of oncogenic transformation increased and the RBEm approached 20. At higher LETs, RBE dropped precipitously. The rapid drop in effectiveness for alpha particles with LETs between 120 and 265 keV/microns implies a lower quality factor than the 20-25 currently considered appropriate when estimating lung cancer mortality.

Alpha Particles↗
PubMed1995

The biological effectiveness of radon-progeny alpha particles. IV. Morphological transformation of Syrian hamster embryo cells at low doses.

Primary explants of Syrian hamster embryo (SHE) cells were exposed to either low-LET 250 kVp X rays or graded single doses of defined high-LET alpha particles (90, 100, 120, 150, 180 and 200 keV/microns), simulating those produced by radon progeny, and monitored for cell inactivation and oncogenic transformation. For the alpha particles the doses delivered ranged from 1 cGy to 1 Gy with an emphasis on doses less than 20 cGy, while for the X rays the doses ranged from 20 cGy to 4 Gy. The dose-response curves for cell killing by alpha particles approximated an exponential function of dose, whereas the X rays produced a curve with a shoulder characteristic of linear-quadratic relationships seen for low-LET radiations. The RBE at 10% survival varied between 3.6-7.0 depending on the LET of the alpha particles, with the RBEm ranging between 7-12. The most effective alpha particles were those with an LET of 120 keV/microns. All radiations produced initial increases in the frequency of morphological transformants, as a function of dose, with a rise to a maximum followed by a plateau in the response which was relatively constant at approximately 2-6 x 10(-3) transformants frequency, expressed per initial cell at risk, had a tendency to decline to parallel the cell survival response. Both the dose at which the maximum frequency of transformants was expressed and the initial slope of the dose-response relationship differed substantially between the different radiation qualities. Maximal transformation per initial cell at risk occurred at doses as low as 1-4 cGy for the 90 and 100 keV/microns particles with the maximum occurring at higher doses (to 16 cGy) as the LET increased toward 200 keV/microns. In contrast, the maximal transformation for 250 kVp X rays was at 50 cGy. The 90 and 100 keV/microns particles, with an RBEm of 60 and 37, respectively, based on the ratios of the initial slopes of the dose-response curves, were the most effective LETs in terms of the ability to induce morphological transformation of SHE cells. When expressed in terms of particle fluence, it appears that in the LET range of radon progeny approximately two to four particle traversals per nucleus are required per killing event, whereas it is at doses corresponding to less than one particle per nucleus that maximal oncogenic transformation is expressed.(ABSTRACT TRUNCATED AT 400 WORDS)

Alpha Particles↗
PubMed1994

Organizational innovations that nourish staff leadership.

Health care is experiencing a paradigm shift that has the potential to redefine traditional roles, systems, and practices. At Albert Einstein Medical Center in Philadelphia, Pennsylvania, the nursing organization has capitalized on this potential and has been energized by the array of opportunities for innovation and experimentation. The results of these efforts suggest that many of these changes not only are positive approaches to patient care but also promote staff leadership and an entrepreneurial spirit at the front line.

Decision Making, Organizational↗
PubMed1992

Collagen metabolism in the murine colon following X irradiation.

Female CBA mice, aged 16 weeks, were irradiated to the total pelvic region with either single doses (5-20 Gy) or two equal fractions (10- to 30-Gy total dose, 24-h interval) of 240 kV X rays. Total protein and collagen synthesis rates, collagen breakdown, and net collagen content of the colon were measured at various times postirradiation using a radioisotope incorporation method and HPLC analysis. Immunohistochemical staining and computerized image analysis were used to assess the relative amounts of collagen types I and III at various times postirradiation, in various regions of the colon. Total protein and collagen synthesis rates were elevated above control levels at 4 and 8 weeks postirradiation, as was collagen degradation. Values had returned to control levels by 16 weeks postirradiation, and there were no further changes up to 71 weeks postirradiation. The net amount of collagen in the colon did not change relative to controls at any time during the investigation. There was, however, increased immunohistochemical staining for collagen type I 52 weeks postirradiation in all regions of the colon and decreased staining of type III in the circular muscle layer and villi. Altered ratios of these two collagen isotypes are consistent with changes in mechanical properties of the tissue.

Animals↗
PubMed1991

Determination of X-ray-induced damage to the murine colon using tissue compliance measurements.

A proctometroscope has been developed to measure the mechanical functioning of the colon in a murine model. A balloon-tipped probe is inserted into the colorectal region of anaesthetized mice and inflated hydraulically, at a constant rate, by a motor-driven syringe. Balloon pressure and volume are monitored, processed and plotted on a X-Y/t recorder. The balloon is inserted within the irradiated area, such that the centre of the balloon is 1 cm proximal to the anus, and inflated up to either a maximum volume of 100 microliters or a maximum pressure of 100 cmH2O, depending on which occurs first. Compliance (delta V/delta P) of the colon was measured at various intervals following X-irradiation, a dose-dependent decrease being observed at 24 weeks. This decrease was progressive with time out to 72 weeks postirradiation. The compliance measured, in both control and irradiated groups, was not dependent on the inflation rate used to make the determination, and no iatrogenic effects have been detected after repeated probing during a long-term study. The use of different anaesthetic agents was also investigated, no significant difference between the compliance of mice anaesthetized with the different agents being detected. Use of this technique provides fully quantitative data on the function of the colon following radiation injury, and provides an alternative to other physiological assays. The technique is non-destructive, rapid, easy to use and non-invasive to the tissue, thus the onset and progression of damage can be followed in each mouse over long postirradiation periods.

Animals↗
PubMed1990

Determination of collagen and protein turnover by high-performance liquid chromatography.

A high-performance liquid chromatographic method is described for the determination of tissue collagen and protein synthesis rates in vivo, together with an index of collagen degradation. The technique utilises post-column reaction with 7-chloro-4-nitrobenzofurazan (NBDCl), which shows higher reactivity towards the secondary amino acids, proline and hydroxyproline, and also exploits differences in absorbance and fluorescence spectra to avoid interference by primary amino acids, including cysteine which reacts rapidly with NBDCl. The relative benefits of using fluorescence or absorbance detection are discussed. A detailed description is given of the steps involved in sample preparation and data for five normal tissues in the mouse are presented using fluorescence detection.

4-Chloro-7-nitrobenzofurazan↗
PubMed1985

Case-mix and cost differences between teaching and nonteaching hospitals.

The case loads of 11 teaching and 20 nonteaching hospitals are compared, using the original 383 diagnosis-related groups (DRGs) to analyze the extent to which case-mix differences contribute to differences in average cost per case. Case-mix differences are concentrated in a small proportion of DRGs. Teaching hospitals have relatively more surgery cases and neoplasms, and nonteaching hospitals have more cases with heart conditions and infectious diseases. Most nonteaching hospitals have a similar case mix, but among the teaching hospitals, there are two distinct case-mix types, one with which only teaching hospitals are correlated, one that correlates with both teaching and nonteaching hospitals. The average cost per case is more than 60% more expensive in teaching hospitals. Only approximately one quarter of this higher cost is accounted for by case-mix differences. The rest results from the fact that patients in the same DRGs cost more, on average, in teaching than in nonteaching hospitals.

Adult↗
PubMed1984

An analysis of hospital case mix, cost, and payment differences for Medicare, Medicaid, and Blue Cross Plan patients using DRGs.

To increase our understanding of case mix as a major contributor to variability in hospital costs, we examined the relationship among case mix, resource consumption, and payments for all Medicare, Medicaid, and Blue Cross Plan patients discharged from 28 hospitals in New York State. Case mix differences among the three payers were found to contribute to differences in overall average cost per case, although residual differences in costs existed at the DRG level. Medicare and Medicaid payments more often covered the actual costs of their patients than did Blue Cross Plan payments. Our results indicate the importance of payer-specific data in the design of effective and equitable reimbursement and cost containment strategies.

Blue Cross Blue Shield Insurance Plans↗
PubMed1982

Impact of a mandatory second-opinion program on medicaid surgery rates.

The effect of the Massachusetts second-opinion program on the volume of elective surgery in the Medicaid population was assessed using two approaches: a study of the program experience and surgery decisions of 2,501 program referrals, and an analysis of Medicaid surgery rates before and after program implementation. Nonconfirmation rates, which averaged 14.5 per cent, varied by procedure from 4 per cent for cholecystectomy to 26 per cent for disc surgery. The patient's surgery decision was related to the outcome of the second-opinion consultation: 85.5 per cent of the confirmed patients had the originally proposed operation, as compared with 31 per cent of the nonconfirmed patients. In the year after program implementation, the program was associated with a 20 per cent reduction in the volume of those procedures covered by the program. The greatest percentage declines were for hysterectomies, meniscectomies, hemorrhoidectomies and tonsillectomies/adenoidectomies. The decline in surgery rates was attributed both to a direct effect on patients referred to the program and to a sentinel effect whereby fewer operations were proposed. We conclude that the mandatory second-opinion program in Massachusetts saved Medicaid $3 to $4 for every dollar spent.

Costs and Cost Analysis↗
PubMed1981

The effect of a thirty per cent reduction in physician fees on Medicaid surgery rates in Massachusetts.

In this paper, we use an interrupted time series analysis to assess the effect of a 30 per cent reduction in the Medicaid reimbursement fee for physician services on the rate at which eight elective surgical procedures were performed in the Massachusetts Medicaid population. Tonsillectomy/adenoidectomy is the only procedure in which there was a statistically significant decline in the rate of surgery in most areas of the state following the fee cut. There is some evidence of an increase in the rate of disc surgeries/spinal fusions. The rate of other procedures increased in some areas of the state and decreased in other areas in the period after the fee cut.

Adenoidectomy↗