Recruitment of 99m-technetium- or 111-indium-labelled polymorphonuclear leucocytes in experimentally induced pyogranulomas in lambs.

The recruitment of polymorphonuclear leucocytes (PMNs) during the development of experimental pyogranulomas induced by Corynebacterium pseudotuberculosis was followed in nine male lambs by scintigraphic examination. Autologous blood PMNs were labelled with 99m-technetium or 111-indium and were re-injected intravenously into infected lambs. The functional properties of the labelled cells were monitored 1) in vitro by measuring their phagocytic and bactericidal activity against C. pseudotuberculosis and their chemotaxis under agarose, and 2) in vivo by following scintigraphically their capacity to accumulate in an inflammatory focus induced by intradermal injection of latex beads coated with Salmonella abortus equi lipopolysaccharide. Following inoculation of corynebacteria into the right ear of lambs, radioactive foci were observed to be localized in the right ear and in the draining lymph nodes during the 4 days following inoculation. Histopathological examination performed 32 h after inoculation confirmed the intense accumulation of PMNs at these sites. With the exception of one animal, which presented visible foci in the neck 14 days postinoculation, no radioactive foci were observed during the later phases of experimental infection, despite the presence of multiple pyogranulomas which were confirmed by bacteriological examination after necropsy of the lambs. Histopathological examination of these lesions revealed layers of fibroblasts, lymphocytes, and macrophages surrounding a necrotic centre. The results of these studies suggest that the contribution of PMNs during the chronic phase of inflammation is considerably reduced in comparison with the acute inflammatory phase of the infectious process.

Ovine mononuclear phagocytes in situ: identification by monoclonal antibodies and involvement in experimental pyogranulomas.

In order to characterize in situ the macrophages present in experimental pyogranulomas induced in lambs with Corynebacterium pseudotuberculosis, a set of monoclonal antibodies (MAbs) was produced following immunization of BALB/c mice with alveolar macrophages from healthy sheep. Three MAbs were retained after two steps of screening using alveolar macrophages, peripheral blood lymphocytes, and polymorphonuclear leukocytes as target cells. Their reactivity was tested not only on macrophages in pyogranulomas but also on sections of various organs in steady-state conditions. One MAb, termed OM1, recognized the monocytes and the majority of cells of the mononuclear phagocyte system in lymphoid and nonlymphoid organs. The two other MAbs, OM2 and OM3, reacted with a subpopulation of alveolar macrophages and with other cell types in tissues, in particular with endothelial cells for the MAb OM2. On sections of experimental pyogranulomas that developed in lymph nodes draining the C. pseudotuberculosis-injected sites, MAb OM1 reacted with all the macrophages distributed in a palisade surrounding the necrotic center of the lesion from day 6 to day 28 postinoculation. The two other MAbs, OM2 and OM3, enabled two types of granulomas to be distinguished: one type was characterized by a large number of epithelioid cells stained by OM2; and the other was characterized by a few OM2-positive macrophages, whereas the OM3-positive cells were more numerous. These results show that macrophages are predominant cells in pyogranulomas and suggest two different histological patterns in the evolution of pyogranulomas induced by C. pseudotuberculosis, according to the immunological status of the host.

Radioisotopic imaging allows optimization of adenovirus lung deposition for cystic fibrosis gene therapy.

Cystic fibrosis is a common, heriditary disease resulting from mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Airway transfer of the CFTR gene is a potential strategy to treat or prevent the lung pathology that is the main cause of morbidity and mortality. Among the vectors used for gene therapy, adenoviruses have shown their ability to transfer the CFTR gene to respiratory epithelial cells, using either instillation or nebulization. Our objective was to characterize the lung deposition of aerosolized adenovirus by quantitative radioisotopic imaging, the only noninvasive technique allowing in vivo quantitation of inhaled drugs. We first labeled an adenovirus expressing human CFTR with the gamma-emitting radioisotope, technetium 99m (99mTc), and determined the best labeling conditions to allow preservation of virus bioactivity. We then administered the radioaerosol to baboons, determined lung regional deposition of 99mTc-labeled adenovirus, and compared the expression of CFTR transcripts 3 and 21 days after inhalation. The expression of vector-encoded mRNA ranged from 4 to 22% with respect to the endogenous CFTR mRNA depending on the lung segments. Moreover, we have developed a model using 99mTc-DTPA (diethylenetriamine pentaacetic acid), which can be used, as an alternative to adenovirus, to determine the profile of lung deposition of the vector. This study demonstrates that scintigraphy is a useful technique to achieve optimization of gene administration to the airways.

Distribution of non-enzymatically bound glucose in in vivo and in vitro glycosylated type I collagen molecules.

Non-enzymatic glycosylation of collagen occurs both in vivo during diabetes and in vitro after incubation with glucose. Glycosylated collagen exhibits altered physicochemical and biological properties which could explain some of the complications of diabetes. To provide a mechanistic explanation of this modification the localization of bound glucose was investigated using NaB[3H]H4 reduction and CNBr cleavage. Glucose fixation is distributed mainly on the alpha 1CB6 peptide after in vitro glycosylation whereas this distribution occurs less specifically during diabetes. It is concluded that fibrillogenesis alteration of in vitro glycosylated collagen is related to glucose fixation on free epsilon NH2 sites normally implied in intermolecular interactions.

Quantitative magnetic resonance and isotopic imaging: early evaluation of radiation injury to the brain.

PURPOSE: Using magnetic resonance (MR) and isotopic imaging to investigate the cerebral alterations after highdose single-fraction irradiation on a pig model. We assessed the nuclear magnetic resonance (NMR) relaxation times as early markers of radiation injury to the healthy brain. METHODS AND MATERIALS: A total of 17 animals was studied; 15 irradiated and 2 unirradiated controls. Pigs were irradiated with a 12 MeV electron beam at a rate of 2 Gy/min. Ten animals received 40 Gy at the 90% isodose, five animals received 60 Gy, and two animals were unirradiated. The follow-up intervals ranged from 2 days to 6 months. T1-weighted scans, T2-weighted scans, and scintigrams were performed on all animals to study neurological abnormalities, cerebral blood flow, and blood-brain barrier (BBB) integrity. T1 and T2 relaxation times were measured in selected regions of interest (ROIs) within the irradiated and contralateral hemispheres. A ratio T1 after irradiation/T1 before irradiation, and a ratio T2 after irradiation/T2 before irradiation, were calculated, pooled for each dose group, and followed as a function of time after irradiation. RESULTS: Scintigraphy visualized the brain perfusion defect and BBB disruption in all irradiated brains. The ratio T2 after irradiation/T2 before irradiation was proportional to the effective dose received. The T2 ratio kinetics could be analyzed in three phases:an immediate and transient phase, two long-lasting phases, which preceded compression of the irradiated lateral ventricle, and edema and necrosis at later stages of radiation injury, respectively. The magnetic resonance imaging (MRI) observations correlated well with histological analysis. CONCLUSION: The results show that quantitative imaging is a sensitive in vivo method for early detection of cerebral radiation injury. The reliability and dose dependence of T2 relaxation time may offer new opportunities to detect and understand brain pathophysiology after high-dose single-fraction irradiation.

Bone kinetics of calcium-45 and pyrophosphate labeled with technetium-96: an autoradiographic evaluation.

The uptake of calcium-45 and of pyrophosphate labeled with the long-lived technetium-96 isotope were compared by means of liquid-emulsion microautoradiograms of the epiphyseal plates of 10-week-old rabbits, at 30 min, and 3 and 48 hr after i.v. administration. For both tracers, thin sections confirm the significant role of the blood supply, especially shortly after injection. However, other more specific mechanisms lead to a mixing of the calcium in the mineral mass and to a linear deposition of technetium facing the osteoid surfaces. These findings suggest that the tropism of tin-reduced technetium pyrophosphate is not governed by the mineral pool but rather by exchanges inside a still poorly calcified organic matrix.

Skeletal uptake of pyrophosphate labeled with technetium-95m and technetium-96, as evaluated by autoradiography.

For animal experimentation, the 95m and 96 technetium isotopes offer many advantages over technetium-99m. Their long physical half-lives and the emission of extranuclear electrons of low penetrating power make it possible to obtain autoradiograms of a great precision. The uptake of technetium stannous pyrophosphate by the epiphyseal plate was studied using liquid-emulsion microautoradiography, 3 hr after i.v. injection into 10-week-old rabbits. Microautoradiograms showed a well-defined and rather specific pattern of localization with intense uptake beneath the epiphyseal disk on the extremities of the vascular buds and a lack of accumulation in the cartilage, whether calcified or uncalcified. In the metaphysis, the label was located where new bone was being laid down and also over the cytoplasm of osteoclasts. We deduce from these results that in normal bone the general distribution of this tracer reflects mainly the arrangement of the blood supply, but the specific sites of accumulation are the bone-forming surfaces and the active resorbing osteoclasts.

Decrease in internal H+ and positive inotropic effect of heptaminol hydrochloride: a 31P n.m.r. spectroscopy study in rat isolated heart.

1. The cardiotonic effect of heptaminol hydrochloride (Hept-a-myl, Delalande) was studied using 31P-nuclear magnetic resonance (n.m.r.) spectroscopy and left ventricular pressure (LVP) measurements in rat isolated hearts. The possibility of this effect being mediated by an intracellular realkalinisation was tested. 2. Isolated hearts were perfused at 10 ml min-1 by the Langendorff method with Krebs-Henseleit solution at 37 degrees C and stimulated at 5 Hz. Mechanical activity was measured as variations of left ventricular pressure (LVP). 31P-n.m.r. spectra were recorded every 2 min. Changes in cardiac adenosine triphosphate (ATP), phosphocreatine (PCr) and inorganic phosphate (Pi) were followed and intracellular pH (pHi) was estimated from the chemical shift of Pi. 3. The effects of heptaminol were tested in different conditions: normoxia, moderate ischaemia, severe ischaemia, and moderate ischaemia in the presence of amiloride or guanidinium chloride as inhibitors of the Na-H exchange. 4. In normoxia, heptaminol induced a cyclic increase of systolic LVP, associated with an increase in Pi. No significant effect on pHi was observed. In changing from normoxia to moderate ischaemia, PCr and systolic LVP decreased; a mild intracellular acidification (pHi 6.96) was obtained. Heptaminol induced a restoration of pHi and increased LVP. In severe ischaemia, the realkalinization effect and the restoration of LVP induced by heptaminol were no longer observed. During moderate ischaemia, Na-H exchange inhibitors decreased pHi and LVP. Heptaminol applied in the presence of these inhibitors was unable to restore pHi and LVP. In severe ischaemia, the realkalinization effect and the restoration of LVP induced by heptaminol were no longer observed. During moderate ischaemia, Na-H exchange inhibitors decreased pHi and LVP. Heptaminol applied in the presence of these inhibitors was unable to restore pHi and LVP. 5. These results suggest that the positive inotropic effect of heptaminol during moderate ischaemia could be related to a restoration of internal pH, possibly mediated by a stimulation of the Na-H exchange.

Scintigraphic in vivo assessment of the development of pulmonary intravascular macrophages in liver disease: experimental study in rats with biliary cirrhosis.

STUDY OBJECTIVES: In regard to nuclear medicine literature reporting lung uptake of colloidal radiopharmaceuticals in patients with liver diseases, it has been hypothesized that liver abnormalities could trigger induction of pulmonary intravascular macrophages (PIMs) in humans normally lacking them. Recently, experimental induction of PIMs in rats in which they are not normally prevalent has been demonstrated to be at the origin of pulmonary hemodynamic alterations with an increased susceptibility to ARDS. If such induction may occur in humans, the risk of pulmonary hemodynamic alterations has to be considered and detected. This study demonstrates in a rodent model of biliary cirrhosis that scintigraphy of phagocytic function as commonly used for liver exploration is a suitable strategy for staging PIM development. DESIGN: Sixty rats were randomized as follows: bile duct section (n = 40), sham operation (n = 10), and no operation (n = 10). The rats were submitted to scintigraphy of phagocytic function every 5 days over 35 days for the assessment of radiocolloid uptake within lung and liver. At day 35, radioactivity of blood was counted and immunohistochemistry was performed on lung specimens. RESULTS: As disease progressed, radiopharmaceutical uptake decreased within the liver, while increasing considerably in the lung. At day 35, lung uptake averaged about 66% as compared to 3% before surgery. Lung histologic findings revealed numerous intravascular mononuclear cells closely related to the monocyte-macrophage lineage. CONCLUSION: Scintigraphy of phagocytic function commonly used for liver scanning could be a suitable strategy for the diagnosis of the induction of PIMs under pathologic situations.

Scintigraphy with J001 macrophage targeting glycolipopeptide. A new approach for sarcoidosis imaging.

Scintigraphy with radiolabeled J001 as a ligand for macrophage targeting is a new approach for sarcoidosis imaging. J001 is a fully characterized acylated peptido-poly (1,3) galactoside isolated from Klebsiella membrane proteoglycans and able to bind electively recruited macrophages. Its physiochemical properties allow rapid absorption by the respiratory tract when this agent, labeled by 99m technetium, is administered as an aerosol. Images are obtained within 3 to 5 h after inhalation. In the present study, we determined the ability of J001 scintigraphy to localize areas of sarcoidosis involvement in 22 patients compared with gallium scanning in ten of them. Nineteen patients underwent bronchoalveolar lavage (BAL) and serum angiotensin-converting enzyme (ACE) assay. J001 scintigraphy was also performed on a control group of six patients with extrathoracic melanoma, in whom J001 scintigraphy was used to evaluate the cutaneous extent of the tumor and the lymph node involvement. In this control group, no fixation appeared in the thoracic area. In the sarcoidosis group, 18 positive results were observed. One stage 0 patient had a mediastinal fixation. Five of the six stage 1 patients had a fixation located in the mediastinum, the lungs, and the wrists. Five of the six stage 2 patients had positive foci located in the mediastinum or the lung areas and in the myocardium in one of them. Six of the nine stage 3 patients had positive J001 scintigraphy occurring in the lungs and/or the mediastinum. One patient had a fixation on the main bronchi. J001 scintigraphy and gallium scanning, performed in ten patients, were positive in seven of them. There were discrepancies between the BAL results and J001 scintigraphy, as well as between the ACE results and J001 scintigraphy. In conclusion, 99mTc-J001 scintigraphy appears to be a sensitive and rapid technique for the imaging of thoracic sarcoidosis at the three stages of the disease.

T2 relaxation time as a marker of brain myelination: experimental MR study in two neonatal animal models.

The progress of myelination in the brain was evaluated by visualization of grey/white matter differentiation on magnetic resonance (MR) images and quantitative analysis of MR data. In vivo quantitative MR imaging was used to monitor the T2 transverse relaxation time changes associated with cerebral development and myelination. The progress of myelination was evaluated using two neonatal animal models, the monkey and the dog, known to mature at very different rates. Three beagles were studied from birth to 4 months of age and nine baboons from 1 to 30 months of age. The T2 values in the frontal, parietal and occipital white matter were calculated and the changes in these values with age were followed. Brain maturation in both species was found to correspond to decreasing T2 values in both grey and white matter. This decrease was observed both in the dog brain and, despite slower maturation, in the baboon brain, and appeared to fit with the myelination process in these models. Exploiting the physicochemical parameters of water in tissues via T2 determination is a convenient and reliable strategy for the documentation of brain development in both experimental approaches and clinical situations.

Experimental MR study of cerebral radiation injury: quantitative T2 changes over time and histopathologic correlation.

PURPOSE: To use the pig brain as a large-animal model to examine the effects of high-dose single-fraction irradiation on MR images, T2 relaxation time, and histologic integrity. METHODS: A total of 24 Meishan pigs were studied: 20 irradiated animals and 4 unirradiated controls. A high dose was delivered to the right hemisphere of the animals, using a 12-MeV electron beam. Ten animals received 40 Gy at the 90% isodose, and 10 animals received 60 Gy. Quantitative measurement of T2 relaxation time was compared with qualitative analysis of T2-weighted images and histologic studies. RESULTS: Quantitative analysis revealed a reproducible increase of the T2 parameter within the irradiated areas. The T2 kinetic could be analyzed in two phases, which appeared before the visualization of ventricle compression, necrosis, and edema. The first is characterized by vascular inflammation and the latter by radiation necrosis and edema. Both are dose dependent. CONCLUSION: These results underline the ability of quantitative MR for early diagnosis of brain radiation lesions in vivo.

Potential of T2 relaxation time measurements for early detection of radiation injury to the brain: experimental study in pigs.

PURPOSE: To investigate the MR T2 relaxation time and histologic changes after a single-fraction 25-Gy dose of radiation to the brain of pigs. METHODS: The right hemisphere of 10 Meishan pigs was irradiated with a single dose of 25 GY at the 90% isodose, using a 12-MeV electron beam. T2 relaxation time was measured within three regions of interest in the brain: those that had received 90%, 70%, and 40% of the total dose, respectively. T2 kinetics over time was compared with histologic studies. RESULTS: Brain T2 values were noted to increase within the irradiated areas. T2 kinetics were analyzed in three phases: an immediate transient phase and two long-lasting phases. These two long-lasting phases were correlated with the detection of ventricular compression and necrosis, respectively. The T2 increase within the 90% region of interest was 19%, 22%, and 26% for phases I, II, and III, respectively. T2 measurements within other regions of interest were not significant. CONCLUSION: Although our results suggest a dose threshold for T2 variations, brain T2 values increased after irradiation at a level at which disease could not be seen on conventional MR images. This illustrates the value of using conventional MR imaging in a quantitative manner to assess molecular tissue abnormalities at earlier stages of developing diseases.

T1 mapping from spin echo and stimulated echoes.

We present an imaging method to obtain a map of the spin-lattice relaxation time. Images were acquired with the same spatial resolution and in the same time as for a regular spin-echo acquisition. The sequence was based on the simultaneous acquisition of a spin echo and several stimulated echoes with the same intensity except for T1 weighting which increases with the interval between the excitation pulse and the readout pulse. T1 values obtained on phantoms were compared to those from the inversion-recovery method and show the accuracy (2%) and the precision (5%) of the method. T1 images of the brain of a healthy volunteer are presented and demonstrate the ability of the method to obtain T1 mapping in vivo in 12 min and without susceptibility artifacts. In vivo and in vitro results were compared to those obtained by a TOMROP sequence in the same acquisition time.

Scintigraphic potentials of J001X acylated poly-galactoside for imaging inflammatory lesions in pigs.

Although several approaches already exist for the imaging of inflammatory foci, new specific strategies providing functional data on the lesions are required to determine the extent of the disease and also to assess anti-inflammatory treatment. In our study, we investigated the scintigraphic potential of 99mTc-J001X, an agent developed for the targeting of macrophages. Due to its well documented and progressive evolution of lesions, a model of radiation-induced inflammation in pigs was chosen. Our results demonstrated the ability of J001X to provide images of inflammatory foci with a high contrast. The contribution of some specific and non-specific parameters possibly involved in the scintigraphic behavior of J001X is discussed.

Lymphoscintigraphy via the targeting of macrophages with 99mTc-J001X poly-galactoside in a model of pyogranulomas developed in sheep lymph nodes.

Lymphoscintigraphy usually involves labeled microparticles or colloids that distribute in the lymph flow. A new strategy for imaging pathological lymph nodes would be the targeting of macrophages recruited in these lesions. The potential for lymphoscintigraphy of the highly diffusible J001X acylated polygalactoside labeled with 99mTc was studied and compared to usual colloidal agents in a model of infectious granulomas developed in sheep. Scintigraphic and histological assessment of the specificity of targeting was performed using a MAb (OM1) raised against ovine macrophages taken as reference. This study has evidenced the ability of J001X specifically to image pathologic lymph nodes and more especially the second lymph node in the same chain with a significant scintigraphic contrast.

Evaluation of possible interference of anti-inflammatory drugs upon scintigraphic imaging with macrophage targeting 99mTc-J001X: effects of methylprednisolone, dexamethasone, indomethacin and methotrexate.

J001X, an acylated poly-(1,3)-galactoside isolated from Klebsiella pneumoniae proteoglycan, has been developed to target cells from the monocyte-macrophage lineage. Recent experimental work and initial clinical trials have proved the potential of this molecule labeled with 99mTc for the scintigraphy of inflammatory foci. In a model of radiation-induced inflammation in pigs, the scintigraphic contrast was observed to be very sensitive to a single injection of methylprednisolone given 12 h before scintigraphy. The present study was undertaken to confirm this effect and to estimate the possible interference of various anti-inflammatory agents on the in vivo targeting of macrophages by J001X. Methylprednisolone, dexamethasone, indomethacin and methotrexate used at an immunosuppressive dose were tested to assess the possible risk of false-negative examinations in patients thus treated. Analysis of the results indicated that among the four drugs tested, only methylprednisolone at 0.5-1 mg/kg could interfere with J001X scintigraphy.

Influence of technetium-99m-labeling conditions on physico-chemical and related biological properties of an acylated poly-galactosidic macrophage targeting agent for inflammation imaging.

The potential of 99m-Tc-J001 for the investigation of inflammatory lesions via the targeting of recruited macrophages (M phi) has already been documented in several experimental models and in human diseases. To achieve a functional imaging of inflammation via M phi targeting, minimal labeled colloid content and high in vivo stability of 99mTc-J001 are essential. The actual specificity of such scintigraphy is closely dependent upon the radiolabeling of only the J001 molecules available for M phi targeting. To develop an appropriate radiopharmaceutical kit, optimization of the labeling conditions was achieved from a series of pilot formulations that were evaluated for radiolabeling efficiency and both in vitro and in vivo 99mTc-J001 stability. Colloids were characterized using autocorrelation spectroscopy and multiangle laser-light scattering, radioactive colloid content of the formulations being deduced from biodistribution studies. This work has made possible the definition of a formulation exhibiting a radiolabeling yield > 97.0%, associated with in vivo stability and minimal colloid formation, thus greatly enhancing the specificity of such macrophage scintigraphy.

Macrophage targeting with 99mTc-labelled J001 for scintigraphy of joint inflammation in ovalbumin-induced arthritis in rabbits.

BACKGROUND AND OBJECTIVE: J001 scintigraphy is a new approach, based on macrophage targeting, developed for tumor and inflammation imaging. J001, a non-pyrogenic acylated poly(1,3)galactoside purified from the membrane of a non-encapsulated strain of Klebsiella pneumoniae associates selectively with macrophages via binding to CD11b and CD14 molecules. Since macrophages play a primary role in inflammatory arthritis processes, J001 labeled with 99mTc appeared to be of interest for the scintigraphic imaging of inflammatory lesions. The purpose of this study was to assess the potential of J001 scintigraphy for imaging inflammatory arthritis in the model of ovalbumin-induced arthritis in rabbits. MATERIAL AND METHODS: Ovalbumin-induced arthritis was developed in 17 rabbits. 99mTc-J001 scintigraphy was performed 4 weeks after arthritis induction in 17 rabbits and was repeated at 6 and 8 weeks in 8 rabbits. 99mTc-J001 and 99mTc-MDP scintigraphy were performed before and 2.5 months after radionuclide synovectomy with the intra-articular injection of a high energy beta-emitting radionuclide (186Re) in 3 rabbits and 186Re (first subjected to a complete decrease of radioactivity) in 3 rabbits. RESULTS: 99mTc-J001 scintigraphy was able to image inflammatory arthritis 4 weeks after induction. J001 scintigraphy demonstrated an increased uptake earlier than MDP, which was maintained at week 8. After radionuclide synovectomy, a clear decrease in the J001 scintigraphy ratio occurred, whereas the MDP scintigraphy ratio was stable. After the intra-articular injection of inactive 186Re, no changes in MDP and J001 scintigraphy ratio appeared. CONCLUSION: 99mTc-J001 scintigraphy is able to image joint inflammation and to assess the response to anti-inflammatory treatment in an experimental model of arthritis.

Women's health in relation with their family and work roles: France in the early 1990s.

In this paper, the health of women aged 30 to 49 years is analyzed according to the family and work roles which they exercise, based on the 1991-1992 French national health survey. Households are classified based on the amount of their material resources, and a variety of measures of health and of health-related behaviors are considered. Looking at each role separately, the 'healthy married', 'healthy mother' and 'healthy worker' effects are very obvious for almost all health measures, and higher household income per unit of consumption is clearly associated with better health of women. The role patterns of women are not evenly distributed across income levels: housewives and lone mothers are more common at the bottom and middle of the income scale than at the top, while working women without children, married or not, are much more common at the top. In health terms, more heterogeneity is attached to role patterns in the middle of the income scale than at either extreme. In the middle stratum, two groups of women stand out as being clearly disadvantaged in comparison with that of married women with children and a job: (1) lone mothers, particularly in terms of mental health conditions, malaise symptoms and health-related behaviour, and (2) housewives, particularly in terms of physical health conditions. At the bottom of the income scale, no significant disadvantage is found for housewives compared to married working mothers, yet their overall health pattern is somewhat negative. At the top of the income scale, married working women without children, as well as single women do feel more often than married working mothers that they suffer from handicap or discomfort. The findings are discussed in terms of role enhancement and role strain, health selection, the nature of the health disadvantage associated with specific role patterns, and the importance of the structural context in the role framework.