Comparative immunopathologic study of hyperacute rejection in naive and sensitized rodent cardiac xenograft models.
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Acute Disease↗
Biomedical subjects
J Cole
Publications and source records attributed to J Cole.
Is breast preservation possible in women with large, locally advanced breast cancers?
Breast conservation therapy is an accepted treatment option for early stage breast carcinoma, but is rarely considered appropriate for locally advanced nonmetastatic lesions. Mastectomy specimens of 46/50 patients treated at the Ochsner Clinic and the Mallinckrodt Institute of Radiology with neoadjuvant chemotherapy prior to mastectomy +/- irradiation were evaluated by a single pathologist to assess tumor response to chemotherapy. Forty percent of this group would potentially have been eligible for breast conservation therapy, using a residual tumor size of < or = 4 cm with negative surgical margins as the criteria. Patients most likely to qualify for breast conservation therapy were those with T3N0-1 lesions (67%). Least likely were patients with skin involvement at diagnosis 4/33 (12%). Tumors with an extensive intraductal component at biopsy often had residual islands of intraductal carcinoma occupying the original tumor volume, even when the invasive component was absent or much reduced. A prospective trial will be required to determine whether or not acceptable local control rates can be obtained after breast conservation therapy for that subset of patients with a favorable response to induction chemotherapy.
Adult↗
Cardiac stress during transurethral prostatectomy.
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Anesthesia, General↗
Mutations which alter splicing in the human hypoxanthine-guanine phosphoribosyltransferase gene.
A large proportion of mutations at the human hprt locus result in aberrant splicing of the hprt mRNA. We have been able to relate the mutation to the splicing abnormality in 30 of these mutants. Mutations at the splice acceptor sites of introns 4, 6 and 7 result in splicing out of the whole of the downstream exons, whereas in introns 1, 7 or 8 a cryptic site in the downstream exon can be used. Mutations in the donor site of introns 1 and 5 result in the utilisation of cryptic sites further downstream, whereas in the other introns, the upstream exons are spliced out. Our most unexpected findings were mutations in the middle of exons 3 and 8 which resulted in splicing out of these exons in part of the mRNA populations. Our results have enabled us to assess current models of mRNA splicing. They emphasize the importance of the polypyrimidine tract in splice acceptor sites, they support the role of the exon as the unit of assembly for splicing, and they are consistent with a model proposing a stem-loop structure for exon 8 in the hprt mRNA.
Base Sequence↗
Comparison of the fracture strengths of ceramometal crowns versus several all-ceramic crowns.
Fracture resistance to forces applied to the incisal edges of four types of anterior crowns was tested. Ceramometal crowns fractured at significantly higher values (720 psi) than the all-ceramic crowns (approximately 360 psi). No significant difference was found among the fracture values of the Dicor crowns, the aluminous porcelain jackets, and the crowns fabricated from Dicor veneered with aluminous body and incisal porcelain.
Aluminum Oxide↗
A comparison of the response of unstimulated and stimulated T-lymphocytes and fibroblasts from normal, xeroderma pigmentosum and trichothiodystrophy donors to the lethal action of UV-C.
Unstimulated T-lymphocytes from normal donors are significantly more sensitive to the lethal effects of UV-C than either stimulated T-lymphocytes or fibroblasts as judged by colony-forming ability. Data from other studies suggest that excision repair is more effective in stimulated than unstimulated T-lymphocytes leading to the prediction that these differences in survival should be minimal in cells established from excision defective donors. The prediction was met with XP6BR, a donor of unknown complementation group. For 3 XP's from complementation group D, however, enhanced survival in stimulated T-cells was observed. With cells from an excision-defective TTD who was included in complementation group D of XP both fibroblasts and unstimulated T-lymphocytes were hypersensitive. For a second excision defective TTD patient who was excluded from complementation group D, the unstimulated T-lymphocytes were more resistant than those of normal donors although the fibroblasts were hypersensitive. These results suggest that the in vitro response of stimulated T-lymphocytes or fibroblasts may not reflect the in vivo response of cells, as measured by the response of unstimulated T-lymphocytes.
Adult↗
UV-C sensitivity of unstimulated and stimulated human lymphocytes from normal and xeroderma pigmentosum donors in the comet assay: a potential diagnostic technique.
We have studied incision-break formation in unstimulated and stimulated populations of human T-lymphocytes using the comet (single-cell microgel electrophoresis) assay. The frequency of strand breaks 1 h after UV-irradiation appears to be far greater in unstimulated than in stimulated lymphocytes from normal donors and the excess of strand breaks was observed for a far longer time after irradiation. This result corroborates the greater sensitivity of UV-C irradiation observed in a colony-forming assay but suggests that the defect may relate to a defect in strand rejoining rather than a defect in incision. Few strand breaks were seen in either unstimulated or stimulated lymphocytes of four xeroderma pigmentosum donors, suggesting that the method may offer a rapid diagnostic assay for XP.
Cells, Cultured↗
Elevated hprt mutant frequency in circulating T-lymphocytes of xeroderma pigmentosum patients.
The mutant frequency to 6-thioguanine resistance in circulating T-lymphocytes from 10 xeroderma pigmentosum patients (including complementation groups D and G and XP variants) has been determined. A highly significantly elevated frequency was observed, compared to age-matched, non-smoking control donors (x 2.1-fold higher than the mutant frequency in normal control donors, adjusted for age and cloning efficiency, p less than 0.001). The mutant frequency of 5 XP heterozygotes was in the normal range, when age, smoking habit and log cloning efficiency were taken into account. A number of possible factors which may account for the elevated mutant frequency seen in the XP donors (including an elevated spontaneous mutation rate, UV mutagenesis of the T-cells as they pass through the skin, an effect of environmental mutagens such as tobacco smoke, or as a consequence of immune deficiency) are discussed.
Adult↗
Clozapine-associated priapism: a case report.
Priapism is a recognized side effect of antipsychotic therapy. Recently, new agents known as atypical antipsychotics, such as clozapine, have been introduced with the intent of ameliorating psychosis without the extrapyramidal side effects associated with standard antipsychotic therapy. Priapism has not been observed previously with atypical antipsychotic therapy. We report a case of veno-occlusive priapism associated with the use of clozapine. This priapistic episode was complicated by the development of recurrent post-ischemic priapism.
Adult↗
Sumatriptan in chronic cluster headache: results of continuous treatment for eleven months.
A 32-year-old man received a total of 480 injections of subcutaneous sumatriptan 6 mg for the treatment of acute attacks of chronic cluster headache over an eleven-month period. Over 90% of the attacks resolved within 10 min of treatment (average 6.8 +/- 3.4). As a comparison, the average duration of 61 attacks occurring over the same period, but not treated with sumatriptan, was 56.1 +/- 20.8 min. This difference was highly significant. There was no clinical evidence of tachyphylaxis, and there were no adverse effects. This is the first report of a long-term treatment of cluster headache with sumatriptan. It is concluded that sumatriptan in this case was an effective and well-tolerated treatment for cluster headache.
Adult↗
Comparing the effects of neonatal intensive care unit intervention on premature infants at different weights.
This study investigated the efficacy of an intervention program in the neonatal intensive care unit (NICU) on the development of premature infants from low socioeconomic status (SES) backgrounds. Sixty premature infants born at a county hospital over an 8-month period and their mothers were the focus of this study. The infants were assigned to either a control group or an experimental group. The experimental group received teaching and reinforcement about their babies' behavior from a child development specialist when they visited the NICU. Of the initial 60 infants, 49 completed the study at 8 months, but because data from only the first born of twin pairs were used, 41 infants were included in the final analysis. Infants were divided into two weight groups: one below and one above 1500 g. There was a significant effect of the intervention on the infants' mental and motor scores at 4 and 8 months. Significant differences on the total Home Observation for Measurement of the Environment (HOME) were noted between the groups. There were some significant differences between intervention and control groups on the interaction of the mother with the infant at 4 months but not in the play situation at 8 months. The lighter premature infants had a greater boost from the intervention than did the heavier premature infants. The intervention had no effect on the mother's perception of her infant's temperament or on her confidence skills. In line with other research findings, the infants who weighed less than 1500 g seemed to have benefited most from the intervention, and the effect of the intervention was most notable at 4 months.(ABSTRACT TRUNCATED AT 250 WORDS)
Child, Preschool↗
Measured steps to outcomes.
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Cholecystectomy↗
Possible association between mutant frequency in peripheral lymphocytes and domestic radon concentrations.
To investigate whether previously found geographical correlations between leukaemia incidence and exposure to radon are reflected in a detectable mutagenic effect on individuals, the frequency of mutations in the hypoxanthine guanine phosphoribosyl transferase gene (hprt) in peripheral blood T lymphocytes was measured in subjects with known domestic radon concentrations. These concentrations were measured in December, 1989, in houses in Street, Somerset, UK, by passive alpha-track radon detectors. 20 non-smoking subjects aged 36-55 years were selected from the patient list at the local health centre on the basis of the radon concentrations in their homes--the range selected varied by a factor of ten. Blood samples for preparation of T lymphocytes were taken in July, 1990. There was a significant association between the log mutant frequency and radon concentration (t = 3.47, p less than 0.01). A second analysis of a further set of radon measurements (October, 1990, to January, 1991), in both living rooms and bedrooms, and repeated mutant frequency determinations also showed a significant relation, which remained significant even after exclusion of the highest frequency and adjustment for subject's age and cloning efficiency. These data must be regarded as preliminary and further more extensive studies should be done to determine whether the observed association is causal.
Acute Disease↗
The mutagenicity of 2-amino-N6-hydroxyadenine to L5178Y tk +/- 3.7.2C mouse lymphoma cells: measurement of mutations to ouabain, 6-thioguanine and trifluorothymidine resistance, and the induction of micronuclei.
2-Amino-N6-hydroxyadenine (AHA) was tested in the mouse lymphoma L5178Y tk +/- assay using the microtitre cloning technique over concentrations from 0.005 micrograms/ml-1 (100% viability) to 6 micrograms/ml (10% viability) as measured by cloning efficiency immediately after treatment. At low, non-toxic concentrations (0.005-0.25 micrograms/ml) a dose-related linear increase in the frequency of ouabain-resistant mutants was seen, in addition to an increase in 6-thioguanine- and trifluorothymidine-resistant mutants. No consistent induction of micronucleated cells was observed in this concentration range. Toxic concentrations (20-90% kill) induced a dose-related increase in micronuclei, while the frequency of ouabain-resistant mutants fell (although it was still highly significantly above the control value). These results suggest that the mechanism of action of AHA depends on the concentration, with point mutations being induced at low, non-toxic doses and detectable chromosome breakage occurring only at higher doses. Both large-colony and small-colony trifluorothymidine-resistant mutants were induced at all concentrations. The utility of using multiple genetic end-points in one cell line and the importance of dose range selection for risk assessment and an understanding of the mode of action of test substances is underlined.
Adenine↗
Comparative human cellular radiosensitivity: III. Gamma-radiation survival of cultured skin fibroblasts and resting T-lymphocytes from the peripheral blood of the same individual.
Skin and blood samples were obtained from 34 donors, for whom there was no indication of abnormal radiosensitivity. From these, in 33 cases both fibroblast and T-lymphocyte cultures were obtained and in 26 cases at least three fibroblast and at least two G0 (resting) T-lymphocyte survival assays were possible. Within this set of results, differences in radiosensitivity between donors were significant for fibroblasts but not T-lymphocytes, although the range of radiosensitivity was similar for the two cell types (D 0.90-1.68 Gy for fibroblasts; 1.26-2.15 Gy for T-lymphocytes). Furthermore, there was little evidence for a correlation in radiosensitivity between the two cell types. These results suggest limitations in the predictive value of conventional measurement of cell survival.
Cell Survival↗
Comparative human cellular radiosensitivity: IV. The increased sensitivity of human neonatal cord blood lymphocytes to gamma-irradiation compared with lymphocytes from children and adults.
We have compared the gamma-irradiation survival of G0 peripheral blood lymphocytes from 18 neonatal cord blood samples in a cloning assay with results from 21 controls (age range 1-65 years and consisting of 20 adults and one child). Using mean inactivation dose as the discriminating parameter, the cord blood cells showed a significantly greater radiosensitivity (mean inactivation dose for pooled data = 1.54 Gy) than the normal controls (mean inactivation dose for pooled data = 1.90 Gy, p less than 0.001). These results confirm and extend earlier work suggesting that T-lymphocytes in newborn children are more radiosensitive than normal controls, and this may have implications for the radiation protection of the unborn child.
Adult↗
A phase I study of a combination of allopurinol, 5-fluorouracil and leucovorin followed by hydroxyurea in patients with advanced gastrointestinal and breast cancer.
Twenty patients with advanced carcinomas of the colorectum, pancreas, stomach, and breast were enrolled in a Phase I study of a sequential administration of 5-fluorouracil-leucovorin (FU-LV) combination followed by hydroxyurea (HU) with allopurinol protection (HALF regimen). As a weekly regimen for 6 weeks, followed by a rest period of 2 weeks, FU was administered intravenously (i.v.) during infusion of a 2-hour i.v. infusion of LV at a dose of 500 mg/m2. Six hours following the FU-LV combination, HU (1 gm/m2) was administered orally. Allopurinol (300 mg every 8 hours, orally) was given the day before and on the day of the administration of the FU-LV combination. The starting dose of FU was 300 mg/m2, with escalations to 900 mg/m2. Mucositis, diarrhea, and hematologic toxicities were mild and sporadic with FU doses up to 750 mg/m2 and occurred in patients who had received prior treatment with FU and/or radiotherapy. Dose-limiting neurocerebellar toxicity was observed in 2 out of 6 patients who received a FU dose of 900 mg/m2. Three additional patients experienced moderate neuromotor toxicity at this dose level. Among 17 patients evaluable for response, partial responses were seen in 3 of the 9 patients with colorectal cancer, 1 of the 3 patients each with carcinoma of breast and pancreas. Three of the 5 responses occurred in patients who had received prior treatment with FU and/or radiation therapy. An FU dose of 750 mg/m2 is recommended for a Phase II trial of the HALF regimen.
Aged↗
Abnormal erythemal response and elevated T lymphocyte HRPT mutant frequency in Cockayne's syndrome.
In three children with Cockayne's syndrome (CS), skin exposed to ultraviolet radiation responded transiently either with erythematous papules or an exaggerated sunburn-like response, without chronic actinic damage. Irradiation monochromator tests demonstrated an abnormal delay or reduction in the threshold to ultraviolet (UVB) irradiation-induced erythema similar to that of xeroderma pigmentosum (XP). As with XP there was an elevated frequency of mutants resistant to 6-thioguanine in circulating T lymphocytes. The mutant frequency in a single obligate heterozygote was normal. In contrast to XP, in the two CS individuals studied, adaptive cell-mediated immunity and natural killer cell function were normal. Because the risk of skin cancer is very high in XP but not in CS, the normal immune function in CS provides evidence that immune surveillance may be important in UV tumorigenesis.
Child, Preschool↗