Frequency of fetal cells in sorted subpopulations of nucleated erythroid and CD34+ hematopoietic progenitor cells from maternal peripheral blood

Fetal cells that circulate in maternal peripheral blood (PB) during pregnancy offer a potential source of nucleated fetal material for noninvasive prenatal diagnosis. Fluorescence-activated cell sorting was used to target two populations of fetal cells: nucleated erythroid cells (NECs; CD71/glycophorin-A+ CD45(lo-int) CD34-) and hematopoietic progenitor cells (CD34+ cells; CD34++ CD71/glycophorin-A- CD45(int)). Fetal cells were detected by fluorescence in situ hybridization (FISH) using directly conjugated chromosome X and Y probes in 65% (13 of 20) of the maternal PBs (fetal karyotype 46,XY). The frequency of fetal cells isolated from the NEC and CD34+ fractions was, respectively, 0 to 14 and 0 to 7 cells per 2 x 10(7) previously frozen maternal cells (approximately 20 mL of blood). In nonfrozen samples, the yield and recovery of fetal cells was moderately improved. Culturing the CD34+ sorted fractions in serum-free media with cytokines improved the quality of the FISH preparations and resulted in a slight expansion in detectable fetal cells. The frequency of fetal cells isolated from cultured CD34+ fractions was 0 to 35 and 0 to 93 cells per 2 x 10(7) previously frozen and nonfrozen maternal PB cells, respectively. These results document the isolation, characterization, and enumeration of fetal cells from the maternal periphery that appear to be present in most, but not all, samples analyzed.     

RhG-CSF-mobilized CD34+ peripheral blood progenitors are myeloperoxidase-negative and noncycling irrespective of CD33 or CD13 coexpression

OBJECTIVE: The purpose of this study was to differentiate between the catabolic effects of interleukin-1 (IL-1) when infused into the central nervous system or into the periphery. SUMMARY BACKGROUND DATA: After injury and infection, IL-1 has been found in the central nervous system. Chronic intracerebrovascular infusion of IL-1 produces protein catabolism, anorexia, and fever. However, IL-1 may act directly on liver and bone marrow to elicit metabolic responses. Although IL-1 is thought to be involved in a number of metabolic responses associated with injury-inflammation, the sites of action are unclear. METHODS: Rats were implanted with chronic infusion pumps and received diluent or three doses of IL-1 infused subcutaneously for 6 days, and a variety of response variables were measured. In a second study, doses were adjusted so that similar systemic catabolic responses were obtained from peripheral and intracerebroventricular infusion of IL-1. The acute-phase responses then were compared in the two groups of animals receiving IL-1 by different routes. RESULT: Subcutaneously infused IL-1 elicited catabolic responses in a dose-response manner. Similar catabolic responses were achieved by infusing one tenth of the dose of IL-1 given subcutaneously into the central nervous system. Although similar systemic responses (protein catabolism, anorexia, fever, and weight loss) were observed with both routes of infusion, the subcutaneous infusion produced a much greater lymphocytosis, elevation in acute-phase reactants, and fall in serum iron and albumin. CONCLUSIONS: The IL-1 appears to have different effects depending on the site of production and site of action. Regionalization of signal proteins such as IL-1 should be taken into consideration when devising specific anticytokine treatment strategies.     

Itraconazole maintenance treatment for histoplasmosis in AIDS: a prospective, multicenter trial

The expression of cytokeratins (CKs) in normal cervical epithelium, low grade squamous intraepithelial lesions (SIL), high grade SILs and squamous cell carcinoma (SCC) were analyzed using four different monoclonal antikeratin antibodies. In normal cervical epithelium, CK 18 showed strong immunoreactivity in basal and parabasal layers. CK 19 and 14 were expressed only in the basal layer while CK 13 was found selectively n the spinal cells. As the lesions progressed from low grade SIL to high grade SIL, immunoreactivity of CK 18, 19 and 14 in the basal cell compartment increased while the expression of CK 13 decreased. In SCC, as well-differentiated tumors showed decreased immunoreactivity for CK 18, 19 and 14 with CK 13 showing a strong and focal (localized) immunoreactivity. Undifferentiated carcinomas totally lacked CK 13 reactivity. Our findings therefore suggest that expression of CK 18, 19 and 14 may be directly related to tumor grade and CK 13 may be a marker of differentiation in cervical lesions.     

Giant cell arteritis in Lugo, Spain, is associated with low longterm mortality

OBJECTIVE: To assess the longterm survival of patients with giant cell arteritis (GCA) in a well defined area in Northwestern Spain. METHODS: A followup study of consecutive biopsy proven patients with GCA diagnosed in Lugo, Spain January 1, 1982-March 31, 1996 was performed. Patients were followed from time of diagnosis until either their death or October 1, 1996. Time and cause of death were reviewed. Statistical methods included standardized mortality ratio (SMR), and Kaplan-Meier product-limit survival analysis. Cox proportional hazard models were used to identify clinical features and laboratory findings associated with survival. RESULTS: By October 1, 1996, full information about 109 biopsy proven patients with GCA (59 men/50 women) was available. The mean age +/- SD at the time of diagnosis was 73.9 +/- 7.3 years for women and 74.1 +/- 5.8 for men (p = NS). After a median followup of 54 months, 22 patients (20.2%) had died. Three died within the first month after diagnosis due to either vascular complications related to GCA or therapy complications. Apart from a history of severe underlying diseases (comorbid condition unrelated to GCA), neither sex nor any clinical features of GCA were significantly associated with an increase in mortality. As in the general population of the same age in Lugo, the majority of deaths were due to cardiovascular and cerebrovascular complications. SMR was 0.80 (95% CI 0.47-1.13). One, 2, 5, and 10 year survival rates were 95, 91, 81, and 62%, respectively. Hazard function was 1.8% at Day 30 after diagnosis and remained low until the end of the first year of treatment. Thereafter, mortality increased slightly. As this function was constant, we applied an exponential model. The estimated risk of death with this model was 5.3% per year. CONCLUSION: Longterm mortality of GCA in our area is low. However, it may be possible to further lower the mortality rate through early diagnosis and careful followup.     

Development of multisensory neurons and multisensory integration in cat superior colliculus

The development of multisensory neurons and multisensory integration was examined in the deep layers of the superior colliculus of kittens ranging in age from 3 to 135 d postnatal (dpn). Despite the high proportion of multisensory neurons in adult animals, no such neurons were found during the first 10 d of postnatal life. Rather, all sensory-responsive neurons were unimodal. The first multisensory neurons (somatosensory-auditory) were found at 12 dpn, and visually responsive multisensory neurons were not found until 20 dpn. Early multisensory neurons responded weakly to sensory stimuli, had long latencies, large receptive fields, and poorly developed response selectivities. Most surprising, however, was their inability to integrate combinations of sensory cues to produce significant response enhancement (or depression), a characteristic feature of the adult. Responses to combinations of sensory cues differed little from responses to their modality-specific components. At 28 dpn an abrupt physiological change was noted. Some multisensory neurons now integrated combinations of cross-modality cues and exhibited significant response enhancements when these cues were spatially coincident and response depressions when the cues were spatially disparate. During the next 2 months the incidence of multisensory neurons, and the proportion of these neurons capable of adult-like multisensory integration, gradually increased. Once multisensory integration appeared in a given neuron, its properties changed little with development. Even the youngest integrating neurons showed superadditive enhancements and spatial characteristics of multisensory integration that were indistinguishable from the adult. Nevertheless, neonatal and adult multisensory neurons differed in the manner in which they integrated temporally asynchronous stimuli, a distribution that may reflect the very different behavioral requirements at different ages. The possible maturational role of corticotectal projections in the abrupt gating of multisensory integration is discussed.     

Hormonal receptors in mammary carcinoma: comparison between quantitative and qualitative methods

Alternatives to the traditional hormone receptor dosages for prognostic evaluation and clinical approach to breast cancer have been proposed for immunohistochemical determinations. For correlation purposes, such procedures were compared in 37 patients presenting 5 to 15 years of survival. Considering 30 fm/mg as the positivity index, the disagreement between both methods reached 35.1% with estrogen and 48.5% with progesterone receptors. When the positiveness level was changed to 20 fm/mg, the discrepancies were reduced to 32% with ER and increased to 57% with PgR. This study leads us to not recommend the immunohistochemical method applied to paraffin sections as an alternative procedure to the dextran-charcoal dosage for prognosis and therapeutic management of mammary carcinoma.     

Body fat and skeletal muscle mass in relation to physical disability in very old men and women of the Framingham Heart Study

BACKGROUND: Low muscle mass has been assumed to be associated with disability, but no studies confirming this association have been published. High body weight and high body mass index, both rough indicators of body fatness, have been shown to increase the risk for disability; however, the specific role of body fatness has not been studied. METHODS: The relations of skeletal muscle mass and percent body fat with self-reported physical disability were studied in 753 men and women aged 72 to 95 years. Cross-sectional data from biennial examination 22 (1992-1993) of the Framingham Heart Study were used. Body composition was assessed by dual-energy x-ray absorptiometry. Disability was scored as any versus none on a 9-item questionnaire. RESULTS: Total body and lower extremity muscle mass were not associated with disability in either men or women. However, a strong positive association between percent body fat and disability was observed. The odds ratio for disability in those in the highest tertile of body fatness was 2.69 (95% confidence interval 1.45-5.00) for women and 3.08 (1.22-7.81) for men compared to those in the lowest tertile. The increased risk could not be explained by age, education, physical activity, smoking, alcohol use, estrogen use (women only), muscle mass, and health status. Analyses restricting disability to mobility items gave similar results. CONCLUSIONS: In contrast to current assumptions, low skeletal muscle mass was not associated with self-reported physical disability. Persons with a high percent body fat had high levels of disability. Because it cannot be ruled out that persons with low skeletal muscle mass dropped out earlier in the study, prospective studies are needed to further assess the relationship between body composition and physical disability.     

Menadione induces changes in the membrane electrical properties associated with downregulation of insulin receptors in human erythrocytes

BACKGROUND AND OBJECTIVE: To investigate the course of the intraocular pressure (IOP) in nonglaucomatous patients with pseudoexfoliation (PSX) syndrome after cataract surgery. PATIENTS AND METHODS: In a prospective age-matched controlled clinical study, 23 consecutive patients with PSX were studied and compared with a control group of 23 patients. The IOP was measured by applanation tonometry preoperatively, and postoperatively on day 1, after 4 weeks, and after 6 months. All patients were operated on with a self-sealing 7-mm scleral tunnel incision, phacoemulsification, and posterior chamber intraocular lens (IOL) implantation. RESULTS: Preoperatively the IOP was similar between both groups (P = .962). At the first postoperative day the IOP was below 22 mm Hg in all cases. After 4 weeks and 6 months a mean decrease of 3.88 mm Hg (P = .001) in the control group and of 3.15 mm Hg (P = .002) in the PSX group was observed; this difference was not statistically significant (P = .543). CONCLUSIONS: At 1 day postoperatively no pressure increase was observed in the eyes with PSX after scleral tunnel incision and phacoemulsification. Six months after cataract extraction with IOL implantation, the tension level decreased in the presence of PSX similarly as in normal eyes.     

Spinal cord neuronal precursors generate multiple neuronal phenotypes in culture

Neuronal restricted precursors (NRPs) () can generate multiple neurotransmitter phenotypes during maturation in culture. Undifferentiated E-NCAM+ (embryonic neural cell adhesion molecule) immunoreactive NRPs are mitotically active and electrically immature, and they express only a subset of neuronal markers. Fully mature cells are postmitotic, process-bearing cells that are neurofilament-M and synaptophysin immunoreactive, and they synthesize and respond to different subsets of neurotransmitter molecules. Mature neurons that synthesize and respond to glycine, glutamate, GABA, dopamine, and acetylcholine can be identified by immunocytochemistry, RT-PCR, and calcium imaging in mass cultures. Individual NRPs also generate heterogeneous progeny as assessed by neurotransmitter response and synthesis, demonstrating the multipotent nature of the precursor cells. Differentiation can be modulated by sonic hedgehog (Shh) and bone morphogenetic protein (BMP)-2/4 molecules. Shh acts as a mitogen and inhibits differentiation (including cholinergic differentiation). BMP-2 and BMP-4, in contrast, inhibit cell division and promote differentiation (including cholinergic differentiation). Thus, a single neuronal precursor cell can differentiate into multiple classes of neurons, and this differentiation can be modulated by environmental signals.