Characterization of a high capacity calcium transport system in mitochondria of the yeast Endomyces magnusii

The Ca2+ transport system of Endomyces magnusii mitochondria has been shown previously to be activated by spermine. Here we report it to be regulated also by low, physiological ADP concentrations, by the intramitochondrial NADH/NAD+ ratio, and by Ca2+ ions. The combination of all these physiological modulators induced high initial rates of Ca2+ uptake and high Ca2+-buffering capacity of yeast mitochondria, enabling them to lower the medium [Ca2+] to approximately 0.2 microM. The mechanisms of stimulation by these agents are discussed.     

Leiomyoma-related bleeding: a classic hypothesis updated for the molecular era

Leiomyomas are an important cause of menorrhagia and other forms of abnormal uterine bleeding. The pathogenesis of this process is largely unknown, however. A classic theory, first suggested by Sampson's work in 1912 (Surg. Gynecol. Obstet., 14, 215-230), states that local dysregulation of the vascular structures in the uterus is responsible for this abnormal bleeding. Recent work demonstrates dysregulation of a number of growth factors in the myomatous uterus. As many of these factors regulate the process of angiogenesis or have other effects on vascular structures, we hypothesize that this dysregulation of growth factors or their receptors provides the molecular mechanism underlying these vascular abnormalities. In turn, these abnormal vessels lead women with leiomyomas to experience menorrhagia. Factors that may prove to be important in this process include basic fibroblast growth factor, vascular endothelial growth factor, heparin-binding epidermal growth factor, platelet-derived growth factor, transforming growth factor-beta, parathyroid hormone-related protein and prolactin. Current treatment regimens for women with leiomyoma-related bleeding depend on manipulation of the steroid hormone environment. By better understanding the pathogenesis of this disease process, therapies directed against growth factor abnormalities may result in better treatment with less harmful side-effects.     

Raised plasma endothelin-1 concentrations in patients with primary hypercholesterolemia without evidence of atherosclerosis

This study investigated the Psychosocial adjustment in 40 patients who received orthotopic liver transplantation (OLT) for several endstage liver diseases. Twenty patients were grafted because they suffered from liver Cancer as well as cirrhosis. Particular attention was paid to evaluating whether cancer could affect recipients' coping with transplant. Each patient underwent a semi-structured interview to obtain information on their psychosocial life, relationship with the donor, organ acceptance and life expectancy. Interview was performed I year after transplantation. A psychodiagnostic evaluation was also performed using a Minnesota Multiphasic Personality Inventory (MMPI) and a Human Figure Test. Psychosocial adaptation in everyday life following liver transplantation seemed good in most of the patients, whatever the indication for transplantation might be. It can he seen that by replacing the diseased organ a high percentage of oncological patients overcame their fear of cancer.     

Lithium treatment causes gliosis and modifies the morphology of hippocampal astrocytes in rats

The biological basis of the clinical efficacy of lithium in the treatment of mental illness has been extensively studied in neurones, but little is known about the effects of the drug on glia. Recently we showed that treatment of rats with clinically relevant doses of lithium chloride results in a 35% increase in the immunocontent of the astrocyte marker GFAP in the hippocampus. Here we studied the cytology of this phenomenon. Rats were treated for 4 weeks with a lithium diet which resulted in serum Li+ concentrations of 0.6-1.2 mmol/l. GFAP immunocytochemistry of the hippocampus revealed a mild gliosis in the CA1 area and the dentate gyrus which was associated with a change in the orientation of astrocytic processes. In control animals astrocyte processes were mainly orientated perpendicular to the stratum pyramidale, whereas in treated animals the cells were predominantly stellar in appearance.     

Rural and urban differences in physician resource use for low-risk obstetrics

OBJECTIVE: To explore the hypothesis that rural obstetricians (OBs) and family physicians (FPs) utilized fewer resources during the care of the low-risk women who initially booked with them than did their urban counterparts of the same specialties. DATA SOURCES/STUDY DESIGN: A stratified random sample of Washington state rural and urban OBs and FPs was selected during 1989. A participation rate of 89 percent yielded 209 participating physicians. The prenatal and intrapartum medical records of a random sample of the low-risk patients who initiated care with the sampled providers during a one-year period were abstracted in detail and analyzed with the physician as the unit of analysis. Complete data for 1,683 patients were collected. Resource use elements (e.g., urine culture) were combined by standardizing them with average charge data so that aggregate resource use could be analyzed. Intraspecialty comparisons for resource use by category and overall were performed. FINDINGS/CONCLUSIONS: Results show that rural physicians use fewer overall resources in caring for nonreferred low-risk-booking obstetric patients than do their urban colleagues. Resource use unit expenditures showed the hypothesized pattern for both specialties for total, intrapartum, and prenatal care with the exception of FPs for prenatal care. Approximately 80 percent of the resource units used by each physician type were related to hospital care. No differences were shown in patterns of care for most clinically important aspects of care (e.g., cesarean delivery rates), and no evidence suggested that outcomes differed. The overall differences were due to specific components of care (e.g., fewer intrapartum hospital days and less epidural anesthesia).     

Midwall fractional shortening is an independent predictor of left ventricular diastolic dysfunction in asymptomatic patients with systemic hypertension

Conventional measures of left ventricular (LV) systolic performance suggest that diastolic dysfunction precedes the development of systolic dysfunction in hypertension. Midwall fractional shortening is a new measure of systolic function that identifies hypertensive patients who have evidence of target-organ damage, impaired contractile reserve, and increased mortality. We therefore sought to determine whether depressed midwall fiber shortening is associated with abnormal diastolic function. Echocardiograms were obtained in 102 otherwise healthy hypertensive patients without treatment with normal conventional measures of systolic function. Of these, 15 had depressed midwall shortening based on previously described normative relations. Patients with depressed midwall shortening had slightly higher blood pressure. Abnormal diastolic function, defined as late (A) LV inflow velocity greater than early (E) velocity, was observed in 33% of those with normal midwall shortening but in 60% of those with depressed shortening (p <0.05). Patients with A/E >1 had lower absolute midwall fiber shortening (15 +/- 3% vs 18 +/- 3%, p <0.0001) but similar endocardial shortening. Patients with abnormal midwall shortening had higher A/E and longer isovolumic relaxation times (both p <0.05). In multivariate analysis, midwall fractional shortening, age, and heart rate were independent predictors (p <0.01) of A/E in a model including blood pressure, LV mass, and endocardial shortening. We conclude that subnormal midwall shortening predicts LV diastolic abnormalities in this population of hypertensive patients with otherwise normal measures of LV systolic function. Contrary to our previous understanding, depressed LV systolic performance, when identified with this newer method, occurs coincidentally with impaired diastolic function.     

Regulation of cardiac myocyte contractile function by inducible nitric oxide synthase (iNOS): mechanisms of contractile depression by nitric oxide

Inflammatory cytokines have been implicated in the reversible depression of cardiac contractile function accompanying local or systemic immune stimulation. Incubation of cardiac myocytes with soluble components in the supernatant from cultured rat lung macrophages activated with endotoxin decreases their contractile response to beta-adrenergic stimulation through the induction of iNOS and the subsequent production of nitric oxide by these cells. In the present study, we characterize the mechanisms underlying NO's attenuation of adrenergic responsiveness in cardiac myocytes. iNOS was induced in cultured ventricular myocytes from adult rats by incubation for 20 h with conditioned medium from lipopolysaccharide (LPS)-activated macrophages. iNOS induction did not induce any alteration in beta-adrenergic receptor density or affinity, Galphai protein abundance, or adenylyl cyclase activity in cultured myocytes. Myocyte exposure to activated macrophage-conditioned medium markedly attenuated the elevation of cAMP in response to isoproterenol (Iso, 2 nM). Induction of iNOS with the macrophage-conditioned medium also potentiated the Iso-induced increase in myocyte cGMP. This cGMP increase was totally abolished by NOS inhibitors. NOS inhibition also returned the attenuated cAMP response to 2 nM Iso to levels observed in control cells. Pre-incubation of the cells in isobutylmethylxanthine (IBMX), a phosphodiesterase inhibitor, also partly reversed the attenuation of cAMP increase with 2 nM Iso in cells expressing iNOS. Brief (15 min) exposure of myocytes to the NO donor, S-nitrosoacetylcysteine (SNAC, 100 micro M) which produced a three-fold increase in intracellular cGMP, also decreased by half the contractile response of cardiac myocytes to Iso (2 nM). We conclude that NO endogenously produced by iNOS decreases the intracellular levels of cAMP in response to beta-adrenergic stimulation in isolated cardiac myocytes, in part through a cGMP-mediated mechanism. This effect may participate in the NO-dependent depression of cardiac function following cytokine exposure.     

Uncertainty analysis methods for comparing predictive models and biomarkers: A case study of dietary methyl mercury exposure

Biologically based markers (biomarkers) are currently used to provide information on exposure, health effects, and individual susceptibility to chemical and radiological wastes. However, the development and validation of biomarkers are expensive and time consuming. To determine whether biomarker development and use offer potential improvements to risk models based on predictive relationships or assumed values, we explore the use of uncertainty analysis applied to exposure models for dietary methyl mercury intake. We compare exposure estimates based on self-reported fish intake and measured fish mercury concentrations with biomarker-based exposure estimates (i.e., hair or blood mercury concentrations) using a published data set covering 1 month of exposure. Such a comparison of exposure model predictions allowed estimation of bias and random error associated with each exposure model. From these analyses, both bias and random error were found to be important components of uncertainty regarding biomarker-based exposure estimates, while the diary-based exposure estimate was susceptible to bias. Application of the proposed methods to a simple case study demonstrates their utility in estimating the contribution of population variability and measurement error in specific applications of biomarkers to environmental exposure and risk assessment. Such analyses can guide risk analysts and managers in the appropriate validation, use, and interpretation of exposure biomarker information.     

Mechanical connections between elastin and collagen

The ligament supporting the leading edge of birds' wings is a connective tissue structure with unusual morphologic and elastic features. Its center section is made of a highly extensible composite of elastin and collagen fibers and its two end sections of nearly inextensible pure collagen; these are joined end-to-end in short interdigitating junctions. Substantial forces are transmitted through the junctions showing that collagen and elastin are mechanically connected. The junctions and elastic segment are sufficiently strong that when the intact ligament is maximally strained, the point of failure is commonly in the collagenous segments or their attachments to the tissues of origin or insertion. Here we outline the morphology and describe static force-length properties of this ligament.     

The rare metastasis of osteosarcoma of a long bone associated with von Recklinghausen''s neurofibromatosis

Benign mesothelioma of the pleura is a very rare tumor. The cells responsible originate from either the mesothelium or the submesothelium. This is why such tumors are described in the literature as fibroma of the pleura, mesothelial fibroma, localized fibrous mesothelioma and monophasic spindle cell tumor. Their growth, is very slow taking several years or even decades. In contrast to the more common malignant mesothelioma of the pleura, it is not related to asbestos exposure. This report deals with a 47-year-old woman patient with a giant benign mesothelioma of the pleura in the region of the right thorax, which was completely removed by thoracotomy.