Rnx deficiency results in congenital central hypoventilation.

The genes Tlx1 (Hox11), Enx (Hox11L2, Tlx-2) and Rnx (Hox11L2, Tlx-3) constitute a family of orphan homeobox genes. In situ hybridization has revealed considerable overlap in their expression within the nervous system, but Rnx is singularly expressed in the developing dorsal and ventral region of the medulla oblongata. Tlx1-deficient and Enx-deficient mice display phenotypes in tissues where the mutated gene is singularly expressed, resulting in asplenogenesis and hyperganglionic megacolon, respectively. To determine the developmental role of Rnx, we disrupted the locus in mouse embryonic stem (ES) cells. Rnx deficient mice developed to term, but all died within 24 hours after birth from a central respiratory failure. The electromyographic activity of intercostal muscles coupled with the C4 ventral root activity assessed in a medulla-spinal cord preparation revealed a high respiratory rate with short inspiratory duration and frequent apnea. Furthermore, a coordinate pattern existed between the abnormal activity of inspiratory neurons in the ventrolateral medulla and C4 motorneuron output, indicating a central respiratory defect in Rnx mice. Thus, Rnx is critical for the development of the ventral medullary respiratory centre and its deficiency results in a syndrome resembling congenital central hypoventilation.

A prediction equation for the estimation of cardiorespiratory fitness using an elliptical motion trainer.

OBJECTIVE: In the United States of America, 6.2 million individuals are using elliptical motion trainers in fitness centres. However, graded exercise test protocols to estimate peak oxygen consumption (VO(2peak)) using elliptical motion trainers have not been developed for the general population. METHODS: Fifty-nine subjects (mean age: 23.5 +/- 4.1 years) were randomly divided into a validation (VAL: n = 39) or cross-validation (XVAL: n = 20) group. Peak oxygen consumption (ml x kg(-1) x min(-1)) was measured via indirect calorimetry on an elliptical motion trainer for both groups. Subjects exercised at 150 strides x min(-1) against a resistance of four and a crossramp of 8%. The resistance was increased every two minutes by two units until exhaustion. For the VAL group, a stepwise regression analysis was used to predict VO(2peak) from resistance, maximal heart rate (HR(max)), body mass index (BMI), height and gender (female = 0, male = 1). RESULTS: The prediction equation derived from this study was VO(2peak) (ml x kg(-1) x min(-1)) = 187.39403 + 12.97271 (gender) - 1.45311 (height) - 1.21604 (BMI) - 0.19613 (HR(max)) + 1.57093 (resistance) (R2 = 0.76, SEE = 4.47, p < 0.05). Using this equation, the predicted VO(2peak) of the XVAL group was 45.18 +/- 6.42 ml x kg(-1) x min(-1), while the measured VO(2peak) was 43.55 +/- 6.23 ml x kg(-1) x min(-1) CONCLUSION: No significant difference was found between the measured and predicted VO(2peak) in the XVAL group. Therefore, it appears this protocol and equation will allow individuals to accurately estimate their VO(2peak) without using direct calorimetry. However future studies should investigate the validity of this protocol with diverse populations.

Enx (Hox11L1)-deficient mice develop myenteric neuronal hyperplasia and megacolon.

The isolated homeobox gene Enx (Hox11L1) is expressed in enteric neurons innervating distal ileum, and proximal and distal colon. Enx-deficient mice develop megacolon with massive distension of the proximal colon. The number of myenteric ganglia, total neurons per ganglion, and NADPH diaphorase presumptive inhibitory neurons per ganglion are increased in the proximal and distal colon, but decreased in the distal ileum of all Enx-/- mice. Enx-/- mice provide a model for human neuronal intestinal dysplasia (NID), in which myenteric neuronal hyperplasia and megacolon are seen. These results suggest that Enx is required for the proper positional specification and differentiative cell fate of enteric neurons.

Concurrent training and pulmonary function in smokers.

This study compared the effects of aerobic, resistance and concurrent aerobic and resistance training on pulmonary function and cardiorespiratory endurance in at-risk smokers. 50 sedentary, male smokers with pulmonary function impairments at risk for developing chronic lung diseases were randomly assigned to an aerobic (AerG;n=12), resistance (ResG;n=13), concurrent (ConG;n=13) or non-exercising control (NexG;n=12) group for 16 weeks. AerG subjects performed 45 min of aerobic exercise at 60%HR(max), ResG subjects performed 8 resistance exercises at 60%1-RM for 3 sets, 15 repetitions while ConG subjects performed both aerobic and resistance exercises. ANOVA revealed no significant difference between the groups in their pre-/post-test changes for FEV(1)/FVC ratio (AerG:-4.13%; ResG:-2.13%; ConG:-0.56%); FEF-50 (AerG:-4.59%; ResG:-7.62%; ConG:5.76%), FEF-75 (AerG:-2.36%; ResG:-7.62%; ConG:10.71%) and FEF 25-75 (AerG:-3.53%; ResG:-6.43%; ConG:7.63%). Significant differences were found between the groups in their pre-/post-test changes for FVC (AerG:8.05%; ResG:7.22%; ConG:11.55%), FEV(1) (Aer:9.60%;ResG:5.13%; ConG:12.10%), PEF (AerG: 11.29%; ResG:7.49%; ConG:20.18%), PIF (AerG:24.80%; ResG:19.41%; ConG:28.15%), IVC (AerG: 9.04%; ResG: 6.21%; ConG:16.35%), FEF-25 (AerG:5.88%; ResG:5.37%; ConG:11.88%) and cardiorespiratory fitness (AerG:25.44%; ResG:11.59%; ConG:22.83%). Post-hoc analysis revealed concurrent and aerobic training were equally effective at improving PIF and cardiorespiratory fitness with concurrent training most effective at improving FVC, FEV(1), PEF, IVC and FEF-25. This suggests synergy between aerobic and resistance exercise in preventing or reducing the detrimental effects of smoking while gaining the unique benefits of each mode of exercise.

Bax-deficient mice with lymphoid hyperplasia and male germ cell death.

BAX, a heterodimeric partner of BCL2, counters BCL2 and promotes apoptosis in gain-of-function experiments. A Bax knockout mouse was generated that proved viable but displayed lineage-specific aberrations in cell death. Thymocytes and B cells in this mouse displayed hyperplasia, and Bax-deficient ovaries contained unusual atretic follicles with excess granulosa cells. In contrast, Bax-deficient males were infertile as a result of disordered seminiferous tubules with an accumulation of atypical premeiotic germ cells, but no mature haploid sperm. Multinucleated giant cells and dysplastic cells accompanied massive cell death. Thus, the loss of Bax results in hyperplasia or hypoplasia, depending on the cellular context.

Extended time-lapse in vivo imaging of tibia bone marrow to visualize dynamic hematopoietic stem cell engraftment.

Homing, engraftment and proliferation of hematopoietic stem/progenitor cell (HSC/HPCs) are crucial steps required for success of a bone marrow transplant. Observation of these critical events is limited by the opaque nature of bone. Here we demonstrate how individual HSCs engraft in long bones by thinning one side of the tibia for direct and unbiased observation. Intravital imaging enabled detailed visualization of single Sca-1+, c-Kit+, Lineage- (SKL) cell migration to bone marrow niches and subsequent proliferation to reconstitute hematopoiesis. This longitudinal study allowed direct observation of dynamic HSC/HPC activities during engraftment in full color for up to 6 days in live recipients. Individual SKL cells, but not mature or committed progenitor cells, preferentially homed to a limited number of niches near highly vascularized endosteal regions, and clonally expanded. Engraftment of SKL cells in P-selectin and osteopontin knockout mice showed abnormal homing and expansion of SKL cells. CD150+, CD48- SKL populations initially engrafted in the central marrow region, utilizing only a subset of niches occupied by the parent SKL cells. Our study demonstrates that time-lapse imaging of tibia can be a valuable tool to understand the dynamic characteristics of functional HSC and niche components in various mouse models.

Characterization of a DNA topoisomerase IIalpha gene rearrangement in adriamycin-resistant P388 leukemia: expression of a fusion messenger RNA transcript encoding topoisomerase IIalpha and the retinoic acid receptor alpha locus.

Previous studies using cloned lines of Adriamycin-sensitive and -resistant P388 murine leukemia cells have suggested that a reduction in DNA topoisomerase II alpha (topo II alpha) enzyme activity and protein levels in drug-resistant cell lines (A. M. Deffie, J. K. Batra, and G. J. Goldenberg, Cancer Res., 49: 58-62, 1989) may be due to an allelic mutation in the topo II alpha gene (A. M. Deffie, D. J. Bosman, and G. J. Goldenberg, Cancer Res., 49: 6879-6882, 1989). The drug-resistant cell lines P388/ADR/3 and P388/ADR/7 express a shortened topo II alpha mRNA transcript in addition to the native transcript present in the drug-sensitive P388/4 cell line. Using complementary DNA probes derived from the coding sequence and 3' untranslated region of the native mouse topo II alpha transcript, we have determined that the shorter 4.5-kilobase topo II alpha transcript expressed in the drug-resistant cell lines contains only 3.5-kilobases of topo II sequence from the 5'-terminus onwards. Using a 3'-rapid amplification of cDNA ends strategy, we have cloned cDNAs representing the 3'-termini of both the native and mutant transcripts from both P388/ADR/3 and P388/ADR/7 cells. DNA sequence analysis revealed that the shorter 4.5-kilobase transcript: (a) encodes topoisomerase II alpha until nucleotide position 3494, at which point the sequence diverges for the remaining 956 bases; (b) contains a polyadenylation signal distinct from the native transcript; and (c) contains an open reading frame predicting a truncated topo II alpha fusion protein. Of great interest was the finding that the non-topo II alpha 956-base sequence in the shorter transcript encodes the promoter, exon I, and part of the first intron of the murine retinoic acid receptor alpha gene locus in the antisense orientation, suggesting that a rearrangement on chromosome 11 in the drug-resistant cells led to a gene fusion event between the loci encoding topo II alpha and retinoic acid receptor alpha.

Relationship of DNA topoisomerase II alpha and beta expression to cytotoxicity of antineoplastic agents in human acute lymphoblastic leukemia cell lines.

The levels of expression of topoisomerase II alpha and topoisomerase II beta were investigated in six established cell lines of human childhood acute lymphoblastic leukemia (ALL) as a function of doubling time, cell cycle distribution, and of sensitivity to the antineoplastic agents Adriamycin and etoposide. The slowest growing cell line, ALL-G, was most sensitive to both drugs, whereas the fastest growing cell line, ALL-C, was 15.3- and 6.4-fold more resistant than ALL-G to Adriamycin and etoposide, respectively. Furthermore, ALL-W, the second most rapidly dividing cell line, was most resistant to both Adriamycin (22.8-fold) and etoposide (14.1-fold). Expression of topoisomerase II alpha varied inversely with doubling time, whereas no correlation was found between topoisomerase II beta levels and doubling time. Expression of topoisomerase II beta varied inversely with that of topoisomerase II alpha. The level of topoisomerase II alpha correlated directly with the percentage of cells in S and G2-M phases, whereas topoisomerase II beta expression varied directly with the number of cells in G1. An inverse correlation was found between the level of expression of topoisomerase II beta and resistance to Adriamycin, whereas a direct correlation was observed between the level of expression of topoisomerase II alpha and resistance to Adriamycin. Studies with etoposide, although not statistically significant, were consistent with the pattern observed with Adriamycin. These findings suggest that in ALL cells, cytocidal activity of Adriamycin and etoposide may be mediated, at least in part, by topoisomerase II beta.

Alumni-based evaluation of a novel veterinary curriculum: are Nottingham graduates prepared for clinical practice?

INTRODUCTION: Outcomes-based education has been the core of the curriculum strategy of the Nottingham School of Veterinary Medicine and Science (SVMS) since its inception in 2006. As part of the ongoing curriculum evaluation, the first two graduating cohorts were invited to provide an appraisal of their preparation by the SVMS curriculum for their role in clinical practice. This paper provides brief accounts of the SVMS curriculum model, the development of the evaluation instrument and the findings of the alumni survey. MATERIALS AND METHODS: The evaluation instrument contained 25 attributes expected of SVMS graduates. Alumni rated their preparation for practice in relation to each attribute. RESULTS: The four highest rated characteristics were compassion for animals and the application of ethics to animal welfare; communication skills; recognising own limitations and seeking help and advice where needed and clinical examination skills. The four lowest rated were clinical case management and therapeutic strategies; dealing with veterinary public health and zoonotic issues; knowledge of current veterinary legislation and dealing with emergency and critical care cases. Free text responses were in line with these quantitative findings. CONCLUSION: The results indicate that this sample of SVMS graduates were satisfied with their undergraduate education and felt well prepared for their role in clinical practice.

A molecular signature of PCA3 and ERG exosomal RNA from non-DRE urine is predictive of initial prostate biopsy result.

BACKGROUND: New screening methods that can add predictive diagnostic value for aggressive (high-grade, Gleason score ⩾ 7) prostate cancer (PCa) are needed to reduce unnecessary biopsies for patients with non-aggressive PCa. This is particularly important for men presenting for an initial biopsy with an equivocal PSA in the 2-10 ng ml(-1) range. PCA3 and ERG are biomarkers that can add predictive value for PCa in urine; however, with a limited utility as a digital rectal exam (DRE) is required. METHODS: First-catch urine samples were collected at six sites from men scheduled to undergo a prostate biopsy. Exosomal RNA was extracted, RNA copy numbers of ERG and PCA3 were measured by reverse transcription-quantitative PCR (RT-qPCR), and the EXO106 score (the sum of normalized PCA3 and ERG RNA levels) was computed. Performance was compared with standard of care (SOC; PSA, age, race or family history) parameters. Contingency table, logistic regression, receiver operating characteristics curve and box-plot analyses were performed. RESULTS: In this cohort (N=195), a dichotomous EXO106 score demonstrated good clinical performance in predicting biopsy result for both any cancer and high-grade disease. For high-grade disease, the negative and positive predictive values were 97.5% and 34.5%, respectively. The discrimination between high-grade and Gleason score ⩽ 6 (including benign) biopsy results by a combination of EXO106 and SOC (area under the curve (AUC)=0.803) was significantly improved compared with SOC without EXO106 (AUC=0.6723, P=0.0009). The median EXO106 score correlated (P<0.001; Spearman's rank order) with histologic grade. CONCLUSIONS: A novel molecular signature (EXO106 score) derived from non-DRE urine demonstrated independent, negative predictive value for the diagnosis of high-grade PCa from initial biopsy for men with 'gray zone' serum PSA levels. Its use in the biopsy decision process could result in fewer prostate biopsies for clinically insignificant disease.

Endocrine responses to chronic androstenedione intake in 30- to 56-year-old men.

In young men, chronic ingestion of 100 mg androstenedione (ASD), three times per day, does not increase serum total testosterone but does increase serum estrogen and ASD concentrations. We investigated the effects of ASD ingestion in healthy 30- to 56-yr-old men. In a double-blind, randomly assigned manner, subjects consumed 100 mg ASD three times daily (n = 28), or placebo (n = 27) for 28 days. Serum ASD, dihydrotestosterone (DHT), free and total testosterone, estradiol, prostate-specific antigen (PSA), and lipid concentrations were measured at week 0 and each week throughout the supplementation period. Serum total testosterone and PSA concentrations did not change with supplementation. Elevated serum concentrations of ASD (300%), free testosterone (45%), DHT (83%), and estradiol (68%) were observed during weeks 1-4 in ASD (P < 0.05). There was no relationship between age and changes in serum ASD (r2 = 0.024), free testosterone (r2 = 0.00), or estradiol (r2 = 0.029) concentrations with ASD, whereas the serum DHT response to ASD ingestion was related to age (r2 = 0.244; P < 0.05). Serum concentrations of high-density lipoprotein cholesterol were decreased by 10% during the supplementation period (P < 0.05). These results suggest that the ingestion of 100 mg ASD, three times per day, does not increase serum total testosterone or PSA concentrations but does elicit increases in ASD, free testosterone, estradiol, and DHT and decreases serum high-density lipoprotein cholesterol concentrations.

Nonlipid formula components and fat absorption in the low-birth-weight newborn.

The relationship between nonlipid formula components and fat absorption in newborns is largely uninvestigated. Two formulas of identical fat blend but different protein quality and acid-base properties were fed to two groups of babies from birth and during 3-5 d balance periods in the third week of life. Babies receiving a formula of higher acidity containing predominantly curd protein absorbed a significantly lower percentage of their fat and nitrogen intake than babies receiving a curd-and-whey protein formula (fat absorptions of 73 +/- 11.0 and 85 +/- 8.0%, means +/- SD, p less than 0.04; N absorptions of 90 +/- 3.0 and 93 +/- 1.0%, p less than 0.03, respectively). The feces of the curd-formula babies contained a smaller proportion of long-chain, saturated fatty acids and a larger proportion of shorter-chain and unsaturated fatty acids. Fatty acid type and triglyceride structure are not the only factors influencing fat absorption in newborns. Other formula components may need modification to achieve maximum fat absorption.

Animal models for antiviral chemotherapy.

Traditionally animal models have formed a vital part of the preclinical evaluation of new forms of antiviral therapy. A variety of models used in the past or potentially useful in the future are considered in this short review. Several valuable and complex questions concerning virus-drug interactions in vivo have been successfully addressed by means of animal models. Better understanding of drug modes of action and virus pathogenesis in the models enable even more accurate predictions to be made for the outcome of antiviral therapy in man. The complexity of virus infections in man is such that animals are likely to remain an important part in drug evaluation for many years. To this end, new developments such as improved techniques in the production of transgenic animals are opening up a variety of completely novel methods for studying inhibitors of a wider group of viruses in vivo including the human immunodeficiency virus. However, the correct interpretation of animal data requires the critical evaluation of animal models. This review will identify several important difficulties which confront those working on antiviral chemotherapy in animals and which must continue to be addressed if confidence in animal data is to be maintained.

Chondroid chordoma--a variant of chordoma. A morphologic and immunohistochemical study.

In 1973, Heffelfinger and coworkers described a variant of chordoma that contained cartilaginous areas indistinguishable from hyaline type chondrosarcoma. They designated these tumors chondroid chordomas and found that they had a better prognosis than classic (nonchondroid) chordomas. Since that time, there has been an ongoing debate over whether chondroid chordoma is best considered a distinct clinicopathologic entity separable from chondrosarcoma or a misdiagnosed chondrosarcoma whose concept developed from the erroneous interpretation of morphology. In an attempt to clarify the issue, the authors used light microscopy and immunohistochemistry to study 12 chondroid chordomas, 38 classic chordomas, and 28 chondrosarcomas that arose in the base of the skull or spine. As a reference, they also analyzed the immunohistochemical profile of fetal notochord, ecchordosis physaliphora, and fetal hyaline cartilage. They found that all chondroid and nonchondroid chordomas were positive for cytokeratin, and the majority were also positive for epithelial membrane antigen (EMA) and carcinoembryonic antigen (CEA). In contrast, none of the chondrosarcomas stained for cytokeratin, EMA or CEA. Vimentin and S-100 were positive in more than 95% of both classic and chondroid chordomas and chondrosarcomas. The immunohistochemical profile of these tumors was similar to the pattern of immunoreactivity of their nonneoplastic counterparts. The authors conclude that chondroid chordomas is a variant of chordoma and should not be confused with chondrosarcoma. Because chondroid chordomas have been reported to have a better prognosis, they felt that this nosologic term should be preserved and that chondroid chordoma should continue to be a focus of clinical and pathologic study.

Effect of oral DHEA on serum testosterone and adaptations to resistance training in young men.

This study examined the effects of acute dehydroepiandrosterone (DHEA) ingestion on serum steroid hormones and the effect of chronic DHEA intake on the adaptations to resistance training. In 10 young men (23 +/- 4 yr old), ingestion of 50 mg of DHEA increased serum androstenedione concentrations 150% within 60 min (P < 0.05) but did not affect serum testosterone and estrogen concentrations. An additional 19 men (23 +/- 1 yr old) participated in an 8-wk whole body resistance-training program and ingested DHEA (150 mg/day, n = 9) or placebo (n = 10) during weeks 1, 2, 4, 5, 7, and 8. Serum androstenedione concentrations were significantly (P < 0.05) increased in the DHEA-treated group after 2 and 5 wk. Serum concentrations of free and total testosterone, estrone, estradiol, estriol, lipids, and liver transaminases were unaffected by supplementation and training, while strength and lean body mass increased significantly and similarly (P < 0.05) in the men treated with placebo and DHEA. These results suggest that DHEA ingestion does not enhance serum testosterone concentrations or adaptations associated with resistance training in young men.

A reliable method for establishing viral infection in the rabbit by intranasal inoculation.

Bovine herpesvirus 1 (BHV-1) infection was established in the rabbit by a novel procedure which involved virus being injected through trephine openings on either side of the nose of anaesthetised animals. This method of intranasal inoculation produced more consistent reactions to BHV-1 inoculation, and both humoral and cell-mediated immune responses to the virus were of greater magnitude compared with those following per naris instillation of virus.

Mechanical performance of standard and cannulated 4.0-mm cancellous bone screws.

The mechanical performance of bone screws is determined by their pull-out strength (holding power), compressive force, stripping torque, yield bending moment, ultimate bending moment, and fatigue strength. These parameters are related to the parameters of the screw design, including major thread diameter, minor thread diameter, thread length, pitch, shaft diameter, cannulation diameter, and material properties. The goal of the study was to theoretically predict the static performance of five 4.0-mm, 45-46-mm-long, cancellous, partially threaded standard and cannulated bone screws and compare the predictions with experimental measurements. A secondary goal was to determine if cannulation of the bone screw diminished its mechanical performance. The predicted values for pull-out force, compressive force, and stripping torque were determined by the thread length, major thread diameter, and thread shape factor. The screws with the largest major thread diameter and longest thread length had the greatest pull-out force, compressive strength, and stripping torque. However, when correcting for the thread length, a higher thread shape factor compensated for a smaller major diameter. The coefficient of determination (r2) for the correlation between the predicted and measured pull-out force improved from 0.75 to 0.90 when the theoretical model included the thread shape factor. The yield and ultimate bending moments are a function of the section modulus and material properties of the screw. The Ace solid screw had the greatest section modulus and yield and ultimate bending moments. The experimental data support the theoretical models for predicting the mechanical performance of bone screws. The design of the bone screws can be optimized on the basis of theoretical modeling. The strong correlation between the predicted and measured parameters allows comparison between bone screws without repeated experimental tests. Theoretical and experimental results show that cannulation of the bone screw did not inherently diminish its mechanical performance.

The nature of small bowel luminal fluid lactase.

The evidence indicating a mucosal source for the jejunal fluid lactase activity of children is so far inconclusive. Samples of jejunal mucosa and the adjacent fluid were obtained simultaneously from 15 children. Lactase activity was measured at pH 5.9 in mucosa and fluid. Fluid activities showed a significant positive correlation with the activity of the corresponding mucosal homogenate but a stronger correlation was found with an enterocyte microvillous membrane fraction prepared from the same homogenate (r = 0.807 and 0.889, respectively). Kinetic and pH optima studies were consistent with a microvillous membrane origin. Fluid activity and pH optimum were not changed detectably when measured in the presence of an enterocyte lysosomal acid lactase inhibitor. Jejunal fluid lactase activity and its properties closely reflect the microvillous membrane enzyme. Lysosomal acid lactase does not contribute measurably to the total lactase activity of jejunal fluid.

Selective sensitization of adriamycin-resistant P388 murine leukemia cells to antineoplastic agents following transfection with human DNA topoisomerase II alpha.

Previous studies have demonstrated decreased levels of DNA topoisomerase II alpha protein and messenger RNA in the Adriamycin-resistant P388 murine leukemia cell line P388/ADR/7 compared to the sensitive P388/4 cell line. An allelic fusion event involving the topoisomerase II alpha and the retinoic acid receptor a genes has been identified in these cells that probably contributes to the decreased topoisomerase II activity in P388/ADR/7 cells. However, this allelic mutation may be a minor contributor or even incidental to the resistance phenotype, since these cells display other candidate mechanisms of resistance, including increased P-glycoprotein, increased glutathione-S-transferase activity and an increased onset of DNA repair. To establish a role for topoisomerase II alpha in mediating the Adriamycin resistance phenotype, complementation of the mutant allele was attempted by transfecting the murine P388/ADR/7 cells with a human topoisomerase II alpha expression construct under the control of the human metallothionein IIA promoter. The majority of transfected cell lines that were obtained by selection in hygromycin B contained copies of the integrated expression construct that were rearranged. Only two of thirty-two transfected cell lines were found to contain a single, unrearranged copy of the human topoisomerase II alpha cDNA. P388/ADR/7 cell lines carrying an integrated, intact human topoisomerase II alpha expression vector were more sensitive to Adriamycin, daunorubicin, mitoxantrone, and etoposide, but not to actinomycin D and vincristine compared to control cells transfected with vector alone or cell lines with rearranged topoisomerase II alpha expression constructs. These findings suggest that topoisomerase II alpha is a selective and significant contributor to multifactorial resistance.

Prenatal, delivery, and infant care under Medicaid in three states.

Medicaid services and expenditures were analyzed for care during the prenatal, delivery, and post-delivery periods in three States--California, Georgia, and Michigan. Uniform data were used from the Health Care Financing Administration's Medicaid Tape-to-Tape project, 1983-84. Results indicate that from 16 to 24 percent of all births in the States of the study, during the study period, were financed by Medicaid. Overall, the study showed that more than one-half of expenditures for the study population were for the delivery hospitalization, and less than 12 percent were for prenatal care. As expected, a substantial portion of expenditures were for high-cost deliveries, up to 41 percent of total delivery payments. From 33 to 41 percent of total Medicaid expenditures for Aid to Families with Dependent Children were for pregnancy, delivery, and newborn care in 1983.