A New Standard DNA Damage (SDD) Data Format.

Our understanding of radiation-induced cellular damage has greatly improved over the past few decades. Despite this progress, there are still many obstacles to fully understand how radiation interacts with biologically relevant cellular components, such as DNA, to cause observable end points such as cell killing. Damage in DNA is identified as a major route of cell killing. One hurdle when modeling biological effects is the difficulty in directly comparing results generated by members of different research groups. Multiple Monte Carlo codes have been developed to simulate damage induction at the DNA scale, while at the same time various groups have developed models that describe DNA repair processes with varying levels of detail. These repair models are intrinsically linked to the damage model employed in their development, making it difficult to disentangle systematic effects in either part of the modeling chain. These modeling chains typically consist of track-structure Monte Carlo simulations of the physical interactions creating direct damages to DNA, followed by simulations of the production and initial reactions of chemical species causing so-called "indirect" damages. After the induction of DNA damage, DNA repair models combine the simulated damage patterns with biological models to determine the biological consequences of the damage. To date, the effect of the environment, such as molecular oxygen (normoxic vs. hypoxic), has been poorly considered. We propose a new standard DNA damage (SDD) data format to unify the interface between the simulation of damage induction in DNA and the biological modeling of DNA repair processes, and introduce the effect of the environment (molecular oxygen or other compounds) as a flexible parameter. Such a standard greatly facilitates inter-model comparisons, providing an ideal environment to tease out model assumptions and identify persistent, underlying mechanisms. Through inter-model comparisons, this unified standard has the potential to greatly advance our understanding of the underlying mechanisms of radiation-induced DNA damage and the resulting observable biological effects when radiation parameters and/or environmental conditions change.

A triple-blind, placebo-controlled randomised trial of the ilioinguinal-transversus abdominis plane (I-TAP) nerve block for elective caesarean section.

This study investigated the efficacy of a new ilioinguinal-transversus abdominis plane block when used as a component of multimodal analgesia. We conducted a prospective, triple-blind, placebo-controlled randomised study of 100 women undergoing elective caesarean section. All women had spinal anaesthesia with hyperbaric bupivacaine, 15 µg fentanyl and 150 µg morphine, as well as 100 mg diclofenac and 1.5 g paracetamol rectally. Women were randomly allocated to receive the ilioinguinal-transversus abdominis plane block or a sham block at the end of surgery. The primary outcome was the difference in fentanyl patient-controlled analgesia dose at 24 h. Secondary outcomes included postoperative pain scores, adverse effects and maternal satisfaction. The cumulative mean (95%CI) fentanyl dose at 24 h was 71.9 (55.6-92.7) µg in the ilioinguinal-transversus abdominis group compared with 179.1 (138.5-231.4) µg in the control group (p < 0.001). Visual analogue scale pain scores averaged across time-points were 1.9 (1.5-2.3) mm vs. 5.0 (4.3-5.9) mm (p = 0.006) at rest, and 4.7 (4.1-5.5) mm vs. 11.3 (9.9-13.0) mm (p = 0.001) on movement, respectively. Post-hoc analysis showed that the ilioinguinal-transversus abdominis group was less likely to use ≥ 1000 µg fentanyl compared with the control group (2% vs. 16%; p = 0.016). There were no differences in opioid-related side-effects or maternal satisfaction with analgesia. The addition of the ilioinguinal-transversus abdominis plane block provides superior analgesia to our usual multimodal analgesic regimen.

Rapid implementation of the repair-misrepair-fixation (RMF) model facilitating online adaption of radiosensitivity parameters in ion therapy.

INTRODUCTION: Treatment planning for ion therapy must account for physical properties of the beam as well as differences in the relative biological effectiveness (RBE) of ions compared to photons. In this work, we present a fast RBE calculation approach, based on the decoupling of physical properties and the [Formula: see text] ratio commonly used to describe the radiosensitivity of irradiated cells or organs. MATERIAL AND METHODS: In the framework of the mechanistic repair-misrepair-fixation (RMF) model, the biological modeling can be decoupled from the physical dose. This was implemented into a research treatment planning system for carbon ion therapy. RESULTS: The presented implementation of the RMF model is very fast, allowing online changes of [Formula: see text]. For example, a change of [Formula: see text] including a complete biological modeling and a recalculation of RBE for [Formula: see text] voxel takes 4 ms on a 4 CPU, 3.2 GHz workstation. DISCUSSION AND CONCLUSION: The derived decoupling within the RMF model allows fast changes in [Formula: see text], facilitating online adaption by the user. This provides new options for radiation oncologists, facilitating online variations of the radiobiological input parameters during the treatment plan evaluation process as well as uncertainty and sensitivity analyses.

Biologically optimized helium ion plans: calculation approach and its in vitro validation.

Treatment planning studies on the biological effect of raster-scanned helium ion beams should be performed, together with their experimental verification, before their clinical application at the Heidelberg Ion Beam Therapy Center (HIT). For this purpose, we introduce a novel calculation approach based on integrating data-driven biological models in our Monte Carlo treatment planning (MCTP) tool. Dealing with a mixed radiation field, the biological effect of the primary (4)He ion beams, of the secondary (3)He and (4)He (Z = 2) fragments and of the produced protons, deuterons and tritons (Z = 1) has to be taken into account. A spread-out Bragg peak (SOBP) in water, representative of a clinically-relevant scenario, has been biologically optimized with the MCTP and then delivered at HIT. Predictions of cell survival and RBE for a tumor cell line, characterized by [Formula: see text] Gy, have been successfully compared against measured clonogenic survival data. The mean absolute survival variation ([Formula: see text]) between model predictions and experimental data was 5.3% ± 0.9%. A sensitivity study, i.e. quantifying the variation of the estimations for the studied plan as a function of the applied phenomenological modelling approach, has been performed. The feasibility of a simpler biological modelling based on dose-averaged LET (linear energy transfer) has been tested. Moreover, comparisons with biophysical models such as the local effect model (LEM) and the repair-misrepair-fixation (RMF) model were performed. [Formula: see text] values for the LEM and the RMF model were, respectively, 4.5% ± 0.8% and 5.8% ± 1.1%. The satisfactorily agreement found in this work for the studied SOBP, representative of clinically-relevant scenario, suggests that the introduced approach could be applied for an accurate estimation of the biological effect for helium ion radiotherapy.

Clinically meaningful blood pressure reductions with low intensity isometric handgrip exercise. A randomized trial.

There exists no examination of what is the minimum anti-hypertensive threshold intensity for isometric exercise training. Twenty two normotensive participants were randomly assigned to training intensities at either 5 % or 10 % of their maximal contraction. Twenty participants completed the study. Clinical meaningful, but not statistically significant, reductions in systolic blood pressure were observed in both 5 % and 10 % groups -4.04 mm Hg (95 % CI -8.67 to +0.59, p=0.08) and -5.62 mm Hg (95 % CI -11.5 to +0.29, p=0.06) respectively after 6 weeks training. No diastolic blood pressure reductions were observed in either 5 % -0.97 mm Hg (95 % CI -2.56 to +0.62, p=0.20) or 10 % MVC +1.8 mm Hg (95 % CI -1.29 to +4.89, p=0.22) groups respectively after training. In those unable to complete isometric exercise at the traditional 30 % intensity, our results suggest there is no difference between 5 and 10 % groups and based on the principle of regression to the mean, this could mean both interventions induce a similar placebo-effect.

Reliable lymphatic drainage to axillary sentinel lymph nodes regardless of tumor location within the breast.

BACKGROUND: This analysis was performed in order to determine whether primary tumor location in breast cancer affects the axillary sentinel lymph node (SLN) identification (ID) rate, the false negative (FN) rate, incidence of axillary nodal metastases, or the number of SLN identified. METHODS: In this prospective multi-institutional study, SLN biopsy was performed on clinical stage T1-2, N0 breast cancer patients using blue dye alone or in combination with radioactive colloid, followed by completion axillary LN dissection. RESULTS: Central tumor location was associated with an improved FN rate, which may be related to reliable drainage from the subareolar lymphatic plexus. Tumor location did not significantly affect the SLN ID rate or the mean number of SLN identified. Medial tumor location was associated with a decreased rate of axillary nodal metastasis. CONCLUSIONS: Breast cancers drain reliably to the axillary lymph nodes regardless of tumor location within the breast.

Defining the optimal surgeon experience for breast cancer sentinel lymph node biopsy: a model for implementation of new surgical techniques.

OBJECTIVE: To determine the optimal experience required to minimize the false-negative rate of sentinel lymph node (SLN) biopsy for breast cancer. SUMMARY BACKGROUND DATA: Before abandoning routine axillary dissection in favor of SLN biopsy for breast cancer, each surgeon and institution must document acceptable SLN identification and false-negative rates. Although some studies have examined the impact of individual surgeon experience on the SLN identification rate, minimal data exist to determine the optimal experience required to minimize the more crucial false-negative rate. METHODS: Analysis was performed of a large prospective multiinstitutional study involving 226 surgeons. SLN biopsy was performed using blue dye, radioactive colloid, or both. SLN biopsy was performed with completion axillary LN dissection in all patients. The impact of surgeon experience on the SLN identification and false-negative rates was examined. Logistic regression analysis was performed to evaluate independent factors in addition to surgeon experience associated with these outcomes. RESULTS: A total of 2,148 patients were enrolled in the study. Improvement in the SLN identification and false-negative rates was found after 20 cases had been performed. Multivariate analysis revealed that patient age, nonpalpable tumors, and injection of blue dye alone for SLN biopsy were independently associated with decreased SLN identification rates, whereas upper outer quadrant tumor location was the only factor associated with an increased false-negative rate. CONCLUSIONS: Surgeons should perform at least 20 SLN cases with acceptable results before abandoning routine axillary dissection. This study provides a model for surgeon training and experience that may be applicable to the implementation of other new surgical technologies.

Assessing the new general competencies for resident education: a model from an emergency medicine program.

The Accreditation Council for Graduate Medical Education (ACGME) has promoted six areas that should be addressed during graduate medical training, or "general competencies" (GCs). According to the ACGME, these GCs should be reflected in the educational processes of all residency programs. In promulgating these competencies, however, the ACGME has not provided examples of core content, methods of implementation, or methods of evaluation. The authors propose a practical method for modifying an existing evaluation format, providing a template other programs could use in assessing residents' acquisition of the knowledge, skills, and attitudes reflected in the GCs.

Accuracy of sentinel lymph node biopsy for patients with T2 and T3 breast cancers.

Although numerous studies have demonstrated that sentinel lymph node (SLN) biopsy can accurately determine the axillary nodal status for early breast cancer some studies have suggested that SLN biopsy may be less reliable for tumors >2 cm in size. This analysis was performed to determine whether tumor size affects the accuracy of SLN biopsy. The University of Louisville Breast Cancer Sentinel Lymph Node Study is a prospective multi-institutional study involving 226 surgeons. The study was approved by the Institutional Review Board of each institution, and informed consent was obtained from all patients. Patients with clinical stage T1-2 N0 breast cancer were eligible for the study. Some patients with T3 tumors were included because they were clinically staged as T2 but on final pathology were found to have tumors >5 cm. This analysis includes 2148 patients who were enrolled from August 1997 through October 2000. All patients underwent SLN biopsy using a combination of radioactive colloid and blue dye injection followed by completion Level I/II axillary dissection. Statistical comparison was performed by chi-square analysis. The SLN identification rate, false negative rate, and overall accuracy of SLN biopsy were not significantly different among tumor stages T1, T2, and T3. We conclude that SLN biopsy is no less accurate for T2-3 breast cancers compared with T1 tumors.

Sentinel lymph node biopsy for breast cancer: impact of the number of sentinel nodes removed on the false-negative rate.

BACKGROUND: Numerous studies have demonstrated that sentinel lymph node (SLN) biopsy can accurately determine axillary nodal status for breast cancer, but unacceptably high false negative rates have also been reported. Attention has been focused on factors associated with improved accuracy. We have previously shown that injection of blue dye in combination with radioactive colloid reduces the false negative rate compared with injection of blue dye alone. We hypothesized that this may be from the increased ability to identify multiple sentinel nodes. The purpose of this analysis was to determine whether removal of multiple SLNs results in a lower false negative rate. STUDY DESIGN: The University of Louisville Breast Cancer Sentinel Lymph Node Study is a prospective multiinstitutional study. Patients with clinical stage T1-2, N0 breast cancer were eligible for enrollment. All patients underwent SLN biopsy using blue dye alone, radioactive colloid alone, or both agents in combination, followed by completion level I and II axillary dissection. RESULTS: A total of 1,436 patients were enrolled in the study from August 1997 to February 2000. SLNs were identified in 1,287 patients (90%), with an overall false negative rate of 8.3%. A single SLN was removed in 537 patients. Multiple SLNs were removed in 750 patients. The false negative rates were 14.3% and 4.3% for patients with a single sentinel node versus multiple sentinel nodes removed, respectively (p = 0.0004, chi-square). Logistic regression analysis revealed that use of blue dye injection alone was the only factor independently associated with identification of a single SLN (p<0.0001), and patient age, tumor size, tumor location, surgeon's previous experience, and type of operation were not significant. CONCLUSIONS: The ability to identify multiple sentinel nodes, when they exist, improves the diagnostic accuracy of SLN biopsy. Injection of radioactive colloid in combination with blue dye improves the ability to identify multiple sentinel nodes compared with the use of blue dye alone.

Dermal injection of radioactive colloid is superior to peritumoral injection for breast cancer sentinel lymph node biopsy: results of a multiinstitutional study.

OBJECTIVE: To determine the optimal radioactive colloid injection technique for sentinel lymph node (SLN) biopsy for breast cancer. SUMMARY BACKGROUND DATA: The optimal radioactive colloid injection technique for breast cancer SLN biopsy has not yet been defined. Peritumoral injection of radioactive colloid has been used in most studies. Although dermal injection of radioactive colloid has been proposed, no published data exist to establish the false-negative rate associated with this technique. METHODS: The University of Louisville Breast Cancer Sentinel Lymph Node Study is a multiinstitutional study involving 229 surgeons. Patients with clinical stage T1-2, N0 breast cancer were eligible for the study. All patients underwent SLN biopsy, followed by level I/II axillary dissection. Peritumoral, subdermal, or dermal injection of radioactive colloid was performed at the discretion of the operating surgeon. Peritumoral injection of isosulfan blue dye was performed concomitantly in most patients. The SLN identification rates and false-negative rates were compared. The ratios of the transcutaneous and ex vivo radioactive SLN count to the final background count were calculated as a measure of the relative degree of radioactivity of the nodes. One-way analysis of variance and chi-square tests were used for statistical analysis. RESULTS: A total of 2,206 patients were enrolled. Peritumoral, subdermal, or dermal injection of radioactive colloid was performed in 1,074, 297, and 511 patients, respectively. Most of the patients (94%) who underwent radioactive colloid injection also received peritumoral blue dye injection. The SLN identification rate was improved by the use of dermal injection compared with subdermal or peritumoral injection of radioactive colloid. The false-negative rates were 9.5%, 7.8%, and 6.5% (not significant) for peritumoral, subdermal, and dermal injection techniques, respectively. The relative degree of radioactivity of the SLN was five- to sevenfold higher with the dermal injection technique compared with peritumoral injection. CONCLUSIONS: Dermal injection of radioactive colloid significantly improves the SLN identification rate compared with peritumoral or subdermal injection. The false-negative rate is also minimized by the use of dermal injection. Dermal injection also is associated with SLNs that are five- to sevenfold more radioactive than with peritumoral injection, which simplifies SLN localization and may shorten the learning curve.

Practical guidelines for optimal gamma probe detection of sentinel lymph nodes in breast cancer: results of a multi-institutional study. For the University of Louisville Breast Cancer Study Group.

INTRODUCTION: Multiple radioactive lymph nodes are often removed during the course of sentinel lymph node (SLN) biopsy for breast cancer when both blue dye and radioactive colloid injection are used. Some of the less radioactive lymph nodes are second echelon nodes, not true SLNs. The purpose of this analysis was to determine whether harvesting these less radioactive nodes, in addition to the "hottest" SLNs, reduces the false-negative rate. METHODS: Patients were enrolled in this multicenter (121 surgeons) prospective, institutional review board-approved study after informed consent was obtained. Patients with clinical stage T1-2, N0, M0 invasive breast cancer were eligible. This analysis includes all patients who underwent axillary SLN biopsy with the use of an injection of both isosulfan blue dye and radioactive colloid. The protocol specified that all blue nodes and all nodes with 10% or more of the ex vivo count of the hottest node should be removed and designated SLNs. All patients underwent completion level I/II axillary dissection. RESULTS: SLNs were identified in 672 of 758 patients (89%). Of the patients with SLNs identified, 403 patients (60%) had more than 1 SLN removed (mean, 1.96 SLN/patient) and 207 patients (31%) had nodal metastases. The use of filtered or unfiltered technetium sulfur colloid had no impact on the number of SLNs identified. Overall, 33% of histologically positive SLNs had no evidence of blue dye staining. Of those patients with multiple SLNs removed, histologically positive SLNs were found in 130 patients. In 15 of these 130 patients (11.5%), the hottest SLN was negative when a less radioactive node was positive for tumor. If only the hottest node had been removed, the false-negative rate would have been 13.0% versus 5.8% when all nodes with 10% or more of the ex vivo count of the hottest node were removed (P =.01). CONCLUSIONS: These data support the policy that all blue nodes and all nodes with 10% or more of the ex vivo count of the hottest SLN should be harvested for optimal nodal staging.

Sentinel lymph node biopsy for breast cancer: a suitable alternative to routine axillary dissection in multi-institutional practice when optimal technique is used.

PURPOSE: Previous studies have demonstrated the feasibility of sentinel lymph node (SLN) biopsy for nodal staging of patients with breast cancer. However, unacceptably high false-negative rates have been reported in several studies, raising doubt about the applicability of this technique in widespread surgical practice. Controversy persists regarding the optimal technique for correctly identifying the SLN. Some investigators advocate SLN biopsy using injection of a vital blue dye, others recommend radioactive colloid, and still others recommend the use of both agents together. PATIENTS AND METHODS: A total of 806 patients were enrolled by 99 surgeons. SLN biopsy was performed by single-agent (blue dye alone or radioactive colloid alone) or dual-agent injection at the discretion of the operating surgeon. All patients underwent attempted SLN biopsy followed by completion level I/II axillary lymph node dissection to determine the false-negative rate. RESULTS: There was no significant difference (86% v 90%) in the SLN identification rate among patients who underwent single- versus dual-agent injection. The false-negative rates were 11.8% and 5.8% for single- versus dual-agent injection, respectively (P <.05). Dual-agent injection resulted in a greater mean number of SLNs identified per patient (2. 1 v 1.5; P <.0001). The SLN identification rate was significantly less for patients older than 50 years as compared with that of younger patients (87.6% v 92.6%; P =.03). Upper-outer quadrant tumor location was associated with an increased likelihood of a false-negative result compared with all other locations (11.2% v 3. 9%; P <.05). CONCLUSION: In multi-institutional practice, SLN biopsy using dual-agent injection provides optimal sensitivity for detection of nodal metastases. The acceptable SLN identification and false-negative rates associated with the dual-agent injection technique indicate that this procedure is a suitable alternative to routine axillary dissection across a wide spectrum of surgical practice and hospital environments.

Preoperative lymphoscintigraphy for breast cancer does not improve the ability to identify axillary sentinel lymph nodes.

OBJECTIVE: To evaluate the role of preoperative lymphoscintigraphy in sentinel lymph node (SLN) biopsy for breast cancer. SUMMARY BACKGROUND DATA: Numerous studies have demonstrated that SLN biopsy can be used to stage axillary lymph nodes for breast cancer. SLN biopsy is performed using injection of radioactive colloid, blue dye, or both. When radioactive colloid is used, a preoperative lymphoscintigram (nuclear medicine scan) is often obtained to ease SLN identification. Whether a preoperative lymphoscintigram adds diagnostic accuracy to offset the additional time and cost required is not clear. METHODS: After informed consent was obtained, 805 patients were enrolled in the University of Louisville Breast Cancer Sentinel Lymph Node Study, a multiinstitutional study involving 99 surgeons. Patients with clinical stage T1-2, N0 breast cancer were eligible for the study. All patients underwent SLN biopsy, followed by level I/II axillary dissection. Preoperative lymphoscintigraphy was performed at the discretion of the individual surgeon. Biopsy of nonaxillary SLNs was not required in the protocol. Chi-square analysis and analysis of variance were used for statistical comparison. RESULTS: Radioactive colloid injection was performed in 588 patients. In 560, peritumoral injection of isosulfan blue dye was also performed. A preoperative lymphoscintigram was obtained in 348 of the 588 patients (59%). The SLN was identified in 221 of 240 patients (92.1%) who did not undergo a preoperative lymphoscintigram, with a false-negative rate of 1.6%. In the 348 patients who underwent a preoperative lymphoscintigram, the SLN was identified in 310 (89.1%), with a false-negative rate of 8.7%. A mean of 2.2 and 2. 0 SLNs per patient were removed in the groups without and with a preoperative lymphoscintigram, respectively. There was no statistically significant difference in the SLN identification rate, false-negative rate, or number of SLNs removed when a preoperative lymphoscintigram was obtained. CONCLUSIONS: Preoperative lymphoscintigraphy does not improve the ability to identify axillary SLN during surgery, nor does it decrease the false-negative rate. Routine preoperative lymphoscintigraphy is not necessary for the identification of axillary SLNs in breast cancer.

Transient stimulation of myelin basic protein gene expression in differentiating cultured oligodendrocytes: a model for 3,5,3'-triiodothyronine-induced brain development.

We compared the regulation of myelin basic protein (MBP) gene expression by T3 in differentiating oligodendrocytes in culture with that previously observed by us in the neonatal rat brain. As in intact brain, expression of the T3R alpha gene preceded that of the T3R beta gene. Although the absence of T3 retarded the rate of accumulation of MBP messenger RNA, the level ultimately attained was similar to that reached in the presence of T3. This relationship mirrored the pattern observed in the neonatal brain. Transient transfection experiments showed that T3 regulates MBP expression at the transcriptional level, but only for a limited period during differentiation. These observations imply that the early rise of MBP messenger RNA is T3 dependent, whereas the terminal levels are maintained independently of T3. Both the T3-dependent and, surprisingly, the T3-independent expression of MBP require the presence of an intact T3 response element. T3 receptor may regulate MBP expression in a ligand-independent manner, or a nuclear factor other than T3 receptor may bind to the T3 response element of MBP to regulate terminal gene expression. These findings support the use of differentiating oligodendrocytes as a model of T3-induced brain development.

Thyroid hormone receptor isoform content in cultured type 1 and type 2 astrocytes.

Immunohistochemical studies previously reported from this laboratory showed that astrocytes in adult rat brain appear devoid of all thyroid hormone receptor (TR) isoforms. These findings, however, contrast with reports of measurable nuclear T3 binding in astrocytes in cell culture. To address this discrepancy, TR protein and messenger RNA (mRNA) content of type 1 and type 2 astrocytes in culture were assayed. Type 1 cells represent astrocytes present in brain in vivo. Type 2 astrocytes differentiate in culture from bipotential progenitor O-2A cells in the presence of serum. Under serum-free conditions, these progenitor cells differentiate into oligodendroglia. Total nuclear T3 binding capacity in both type 1 and type 2 astrocytes was approximately 3000 sites/cell. Northern blots showed the presence of mRNA for TRbeta1, TRalpha1, and TRalpha2 in type 2 cells but failed to reveal the presence of these mRNAs in type 1 astrocytes. Moreover, Northern blots also failed to reveal TRbeta2 mRNA in both type 1 and type 2 astrocytes. These findings, therefore, raised a question as to which receptor isoform was responsible for the nuclear binding capacity observed in type 1 astrocytes. As anticipated, immunocytochemical analysis demonstrated prominent nuclear signals for TRbeta1, TRalpha1, and TRalpha2 mRNA in type 2 astrocytes but failed to demonstrate TRbeta1, TRalpha1, or TRalpha2 in type 2 astrocytes. Application of RT-PCR, however, revealed the presence of low levels of TRbeta2 mRNA in type 1 astrocytes. When stained with a specific anti-TRbeta2 antiserum, both type 1 and type 2 astrocytes showed a strong fluorescent signal concentrated in the nucleus. These data indicate that under the special conditions of cell culture, expression of the TRbeta2 isoform in type 1 accounts for the measured nuclear T3 binding capacity.

Immunofluorescent localization of thyroid hormone receptor isoforms in glial cells of rat brain.

The three currently recognized T3 binding thyroid hormone receptor (TR) isoforms, TR alpha 1, TR beta 1, and TR beta 2, arise from two distinct genes (alpha and beta), whereas two closely related non-T3-binding receptor variants, collectively designated TR alpha 2, arise from alternate splicing of the alpha gene transcript. Using a panel of specific antisera to these isoforms we have assessed the presence or absence of TRs in oligodendrocytes and astrocytes of rat cerebrum and cerebellum. Inferences as to colocalization of the receptor isoforms and cell-specific marker proteins were based on immunohistochemical analysis of the differential emissions of paired immunofluorescent probes. Antisera against myelin basic protein (MBP) identified oligodendroglia, and glial fibrillary acidic protein identified astrocytes. MBP-positive oligodendrocytes displayed positive fluorescent signals with each of the three TR isoform-specific antisera and the antiserum to the receptor variants. These findings are consistent with the concept that the MBP gene is a direct target for thyroid hormone action. TR immunoreactivity appeared to localize primarily to the nuclei of these cells. In contrast, we observed no immunofluorescent signals for any of the TR isoforms in glial fibrillary acidic protein-positive astrocytes. These findings raise the possibility that any effect of thyroid hormone on astrocyte function and structure is mediated indirectly as a result of interaction of thyroid hormone with receptors situated in nonastrocyte cells or as a result of nonnuclear mechanisms.

Prediction of maximum exercise tolerance in patients with COPD.

Exercise tolerance in patients with COPD is difficult to predict from measurements of lung function. We examined multiple physiologic and psychosocial variables in an attempt to predict exercise performance in a group of patients with COPD enrolled in a clinical trial of pulmonary rehabilitation. A total of 119 patients (FEV1 = 1.41 +/- 0.64 L) were divided randomly into either a study group (group A, n = 58) or validation group (group B, n = 61). Stepwise multiple regression in group A revealed that peak oxygen uptake (peak VO2) was predicted best by the following equation: Peak VO2 (L/min) = (0.0327 x DCO) + (0.0040 x MVV)-(0.0156 x peak-exercise VD/VT) + (0.0259 x resting VE) + 0.848; r = 0.90; SE = 0.233 L/min. This equation was then cross-validated in group B. It demonstrated excellent validity: measured peak VO2 (L/min) = (1.13 x predicted peak VO2)-0.0891; r = 0.90; SE = 0.239 L/min. We conclude that exercise tolerance was predicted reasonably well from measurements of lung function and gas exchange in this group of patients with COPD. However, the variability of the prediction would limit its usefulness in individual patients.

Fine-scale variability of lanosol and its disulfate ester in the temperate red algaNeorhodomela larix.

Aqueous extraction and HPLC separation techniques were used to quantify two major bromophenols naturally present in the red algaNeorhodomela larix: lanosol (2,3-dibromo-4,5-dihydroxybenzyl alcohol) and its 1,4-disulfate ester. Maximum concentrations of each compound were as high as 1.5% on a wet mass basis. The within-plant distributions of lanosol and its ester were highly variable on centimeter scales: adjacent portions often varied by an order of magnitude in bromophenol content. Some bromophenol variation was related to algal phase, location within the algal thallus, and reproductive status. Bromophenol concentrations were higher in exterior vegetative regions and some reproductive structures (cystocarps and tetrasporangial branchlets) than in interior vegetative regions or male reproductive structures (spermatangial stichidia). In contrast to results reported for harvestedN. larix, there was no evidence that the intactin situ algae released either compound into seawater.