DNA repair in late-passage human cells.

Monolayer cultures of WI-38 cells from passages 18 to 60 were exposed to ultraviolet radiation, or to N-acetoxy-AAF, or to gamma-rays. The cultures were incubated in 3H-dThd, and unscheduled DNA synthesis--a measure of DNA repair--was measured radioautographically. Late passage cultures showed less repair, and many cells showed none. Double-label radioautographs indicated that there is an excellent correlation between cells that do scheduled synthesis and cells that do unscheduled synthesis. We interpret our results as indicating that failure of repair is not a causal event in the failure of late passage cells to divide, but that as cells age the ability to do the many coordinated steps in repair declines.     

Serologic and molecular investigations of a chimera

A chimeric individual possesses two or more genetically distinct cell populations. Although the chimerism may not be evident in all gene systems, various loci display greater numbers of alleles than genetically "normal" individuals. The proposita was referred for further laboratory investigation due to a mixed-field ABO blood group reaction following routine antenatal testing. Various molecular (HLA class II, ABO genotyping, and 10 short tandem repeat [STR] microsatellites) and serologic (HLA class I and red cell blood groups) typing techniques were employed to investigate a number of polymorphic loci located on different chromosomes. Chimerism was identified in 8 out of the 14 chromosomes tested: chromosome 1 (Duffy), 6 (HLA class I and II), 9 (ABO), 11 (HUMTH01), 12 (HUMPLA2A1), 15 (HUMFES/FPS), 18 (Kidd) and 21 (D21S11). The proposita was determined to be a probable dispermic chimera, based on the results of the serology and molecular studies.     

Animal model of neutropenia suitable for the study of dual-phagocyte systems.

When two sets of phagocytic cells participate simultaneously in the inflammatory process and bacterial killing, the relative contribution of each cell type is difficult to ascertain. The use of cell-specific antibody will permit selective depletion of one phagocyte population. We describe an experimental model of granulocytopenia which utilizes the immunoglobulin G fraction of an antigranulocyte serum. This material markedly depleted circulating polymorphonuclear leukocytes (PMN); within 2 h after injection of antigranulocyte globulin, PMN counts were at 19% of original levels and remained significantly depressed for 24 h. Granulocyte recruitment was also impaired, with only 5 x 10(3) PMN appearing in the lungs in response to an aerosol of Klebsiella, compared to 4.17 x 10(5) PMN in control animals (P less than 0.01). Most importantly, alveolar macrophages retained normal viability (97% versus 94% for control value, P not significant) normal phagocytic function, and normal bactericidal capacity. Antigranulocyte globulin is thus a valuable tool for the study of bacterial defense mechanisms.     

Initial evaluation of a continuous speech recognition program for radiology

The aims of this work were to measure the accuracy of one continuous speech recognition product and dependence on the speaker's gender and status as a native or nonnative English speaker, and evaluate the product's potential for routine use in transcribing radiology reports. IBM MedSpeak/Radiology software, version 1.1 was evaluated by 6 speakers. Two were nonnative English speakers, and 3 were men. Each speaker dictated a set of 12 reports. The reports included neurologic and body imaging examinations performed with 6 different modalities. The dictated and original report texts were compared, and error rates for overall, significant, and subtle significant errors were computed. Error rate dependence on modality, native English speaker status, and gender were evaluated by performing ttests. The overall error rate was 10.3 +/- 3.3%. No difference in accuracy between men and women was found; however, significant differences were seen for overall and significant errors when comparing native and nonnative English speakers (P = .009 and P = .008, respectively). The speech recognition software is approximately 90% accurate, and while practical implementation issues (rather than accuracy) currently limit routine use of this product throughout a radiology practice, application in niche areas such as the emergency room currently is being pursued. This methodology provides a convenient way to compare the initial accuracy of different speech recognition products, and changes in accuracy over time, in a detailed and sensitive manner.     

Changes in maternal and newborn lymphocyte reactivity in reciprocal mixed lymphocyte cultures during the postpartum period

Reciprocal one-way mixed mother-newborn lymphocyte cultures (MMNLC) containing alternatively maternal or newborn responding (R) or stimulating (S) cells were investigated in both directions in primiparae at three different times: a few hours after delivery, and at 4 and at 16 weeks. Cultures were grown in the presence of maternal and pooled control serum prepared from the blood of five to eight unrelated healthy donors. Four weeks after delivery in maternal and in control serum a significant increase in MMNLC reactivity could be observed, which disappeared at 16 weeks when a pronounced decline in MMNLC values in both directions was found. The suppressive effect of maternal serum was more pronounced at delivery, still evident 4 weeks later, and insignificant after 16 weeks. The results of this study suggest that 4 weeks after delivery, maternal sensitization to fetal histocompatibility antigens can be detected in primiparae with MMNLC; and that 16 weeks later, this was no longer detectable with the same test.     

Behavioral treatment of essential hypertension: a comparison between cognitive therapy and biofeedback of heart rate

The efficacy and the mechanisms of action of two behavioral treatments for essential hypertension were compared: cognitive group therapy for anger control and biofeedback for heart rate control. The cognitive therapy aimed at lowering the "general anger" level and helping overt expression of "anger out;" heart rate biofeedback aimed at slowing heart rate in stress situations. Ninety-seven essential hypertensive patients were randomly assigned to three groups; after 20 dropouts, 77 patients fully participated in the study: cognitive treatment (N = 30), biofeedback (N = 27), and control (no treatment, N = 20). The treatments were held in 17 weekly sessions; during treatment, blood pressure was measured once a month, and during follow-up after 1 and 6 months. The anger level and heart rate control were assessed at the beginning and the end of treatment. The main results were: 1) a significant decrease of blood pressure for both treatments as compared with control, 2) a significant decrease of blood pressure with heart rate biofeedback as compared with cognitive therapy, and 3) a better control in anger achieved with cognitive therapy and a lesser control in heart rate as compared with biofeedback.     

Monoclonal antibody purified beta 2-microglobulin: heterogeneity revealed by radioimmunoassay

A monoclonal antibody, CMRF1, to human beta 2-microglobulin (beta 2m) was used to purify antigen to develop an in-house beta 2m radioimmunoassay. This immunoadsorption purified material was used to prepare a rabbit anti-beta 2m serum and was radiolabelled for the radioimmunoassay. The assay compared favourably with a widely used commercial radioimmunoassay but the immunological potency of the in-house standard was lower than that of the commercial reagent. This potency difference was not accounted for by antigenic denaturation. Subsequent two-dimensional gel electrophoresis revealed a second 12,000 dalton protein with a higher isoelectric point than beta 2m in the immunoadsorption purified material, which was also present, although in lesser amounts, in the commercial product. The different relative content of the additional 12,000 dalton protein appeared to explain the immunological potency difference between the in-house and the commercial standard. These results strengthen suggestions that there may be some heterogeneity or polymorphism in human beta 2m.     

Effects of tibolone on lipoprotein(a) and HDL subfractions

Objective: To determine the effects of tibolone, a synthetic steroid used to alleviate climacteric symptoms and prevent osteoporosis, on lipoprotein metabolism, with particular reference to lipoprotein(a) levels and HDL subfraction profiles.Design: Thirty nine postmenopausal women were treated with tibolone (Livial) 2.5 mg/day for 6 months and fasting serum lipoprotein levels were estimated at 0, 2, 4 and 6 months. Results: Lipoprotein(a) levels were reduced significantly over the 6 months from a median level of 245 (range <60–780) mg/I to 152 (range <60–530) mg/l, a reduction of 39% in the median level. A decrease was observed in approximately two thirds of the women. Reductions were noted in all 6 subjects whose pretreatment levels were high, although concentrations remained at a level associated with increased risk in all but one. There were significant decreases in triglycerides and VLDL cholesterol and no significant change in LDL cholesterol. There was a significant reduction of 18% in HDL cholesterol and a 26% reduction in the HDL₂:HDL₃ ratio. Conclusion: The reduction in lipoprotein(a) levels may have a beneficial effect on cardiovascular risk, which could go some way towards balancing the potentially adverse effect on the cardiovascular system caused by the reduction in HDL cholesterol.