The retinal nerve fiber layer in normal and glaucomatous eyes. II. Correlations

The retinal nerve fiber layer is different in normal and glaucomatous eyes. We correlated semi-quantitative data of the retinal nerve fiber layer of 398 eyes with chronic primary open-angle glaucoma and of 234 normal eyes with the intra- and parapapillary morphometric signs and with the perimetric indices. The three parameters "sequence of the fundus sectors concerning the best visibility of the retinal nerve fiber bundles", "visibility of the nerve fiber bundles", and "localized defects" were significantly (p less than 0.001) correlated to 1) area of the neuroretinal rim as a whole and in four different optic disc sectors, 2) neuroretinal rim width determined every 30 degrees, 3) optic cup area, diameters and form, 4) horizontal and vertical cup/disc ratios and the quotient of the horizontal to vertical cup/disc ratio, 5) area and width of zone "Alpha", zone "Beta", and the total parapapillary chorio-retinal atrophy, 6) diameter of the retinal vessels, 7) grade of a "tesselated fundus", and 8) the visual field loss. If only the inferior temporal and the superior temporal sectors were considered, the retinal nerve fiber bundles were less visible in that sector with the largest notch in the neuroretinal rim, the smaller neuroretinal rim area and width, the thinner retinal vessels, and the larger zone "Alpha", zone "Beta", and total parapapillary chorio-retinal atrophy. The glaucomatous changes in the retinal nerve fiber layer are correlated in time and location with the intra- and parapapillary and the perimetric alterations. Evaluation of the retinal nerve fiber layer is a useful method to detect a glaucomatous optic nerve damage.(ABSTRACT TRUNCATED AT 250 WORDS)     

Connective tissue growth factor expression and Smad signaling during mouse heart development and myocardial infarction.

Connective tissue growth factor (CTGF) is reported to be a target gene of transforming growth factor beta (TGFbeta) and bone morphogenetic protein (BMP) in vitro. Its physiological role in angiogenesis and skeletogenesis during mouse development has been described recently. Here, we have mapped expression of CTGF mRNA during mouse heart development, postnatal adult life, and after experimental myocardial infarction. Furthermore, we investigated the relationship between CTGF and the BMP/TGFbeta signaling pathway in particular during heart development in mutant mice. Postnatally, CTGF expression in the heart became restricted to the atrium. Strikingly, 1 week after myocardial infarction, when myocytes have disappeared from the infarct zone, CTGF and TGFbeta expression as well as activated forms of TGFbeta but not BMP, Smad effector proteins are colocalized exclusively in the fibroblasts of the scar tissue, suggesting possible cooperation between CTGF and TGFbeta during the pathological fibrotic response.     

A controlled family history study of bulimia

Using the family history method, we assessed the morbid risk for psychiatric disorders in the first-degree relatives of 69 probands with bulimia, 24 probands with major depression, and 28 nonpsychiatric control probands. The morbid risk for major affective disorder among the first-degree relatives of the bulimic probands was 32%, significantly greater than that found in the nonpsychiatric control probands. The rate of familial major affective disorder was significantly greater in bulimic probands who had a history of major affective disorder themselves than in bulimic probands without such a history - but the latter group, in turn, displayed significantly higher rates than the nonpsychiatric control probands. Eating disorders were slightly, but not significantly, more prevalent in the families of bulimic probands than nonpsychiatric control probands. We present two alternative hypotheses which might explain these findings.     

Improvement in histological diagnosis of primary hyperparathyroidism with a monoclonal antiparathyroid antibody

The monoclonal antiparathyroid antibody E11 reacts with a glycoprotein of high molecular weight, which acts as a calcium receptor on the surface of parathyroid cells and mediates calcium regulation of parathyroid hormone (PTH) release. Reduced expression of the calcium receptor has been implicated as a cause of the defect in PTH regulation in the pathological parathyroid parenchyma of patients with hyperparathyroidism (HPT). The present study evaluated the efficacy of immunostainings with the E11 antibody in comparison with routine histopathological methods including staining by the oil red O technique for histological discrimination between normal and pathological parathyroid glands. Parathyroid tissue from euparathyroid individuals invariably presented intense and homogeneous surface staining, with the antibody on virtually all chief cells, while the pathological glands from patients with HPT consistently showed heterogeneous and reduced immunostaining. Even minimally enlarged pathological glands from individuals with mild hypercalcemia and the normal-sized glands associated with adenomas displayed parathyroid chief cells with reduced antibody reactivity. The monoclonal antiparathyroid antibody should constitute a useful tool in parathyroid histopathology not only by its ability to identify the parathyroid tissue, but also by directly demonstrating the functionally normal and abnormal cells within the parathyroid tissue.     

The University of Missouri-Kansas City School of Medicine: thirty-five years of experience with a nontraditional approach to medical education.

The University of Missouri-Kansas City (UMKC) School of Medicine is a public medical school that opened in 1971 in response to a need to train more physicians in Missouri. As a six-year, integrated, combined-degree program leading to the baccalaureate and medical degrees, the school offers an innovative, nontraditional approach to medical education. In the past 35 years, UMKC has graduated over 2,400 physicians who are successful according to outcomes measures used at other medical schools. With recent interest in reforming medical education to prepare physicians for a changing world, a review of alternative models may be especially instructive.UMKC's academic plan offers a blueprint for the curriculum plan and governance of the school. The plan is built on four hallmarks: (1) a combined baccalaureate/MD program, (2) early exposure to clinical medicine, (3) small-group learning through the docent system, and (4) a continuing ambulatory care clinic experience for four years.This article catalogs the results of this plan including student, faculty, and graduates' perceptions of and satisfaction with the school's educational approach, students' achievement on licensing examinations and in the residency match, graduates' performance in residency programs, and their subsequent career patterns. The authors also discuss lessons learned and adjustments made in response to local needs in the context of a changing environment in education, health care, and health care delivery while continually improving the school's nontraditional approach to medical education. These include changes in basic and clinical science instruction, student assessment, faculty development, and funding and governance.     

Presynaptic short-term depression is maintained during regulation of transmitter release at a GABAergic synapse in rat hippocampus

To examine possible interactions between fast depression and modulation of inhibitory synaptic transmission in the hippocampus, we recorded from pairs of synaptically connected basket cells (BCs) and granule cells (GCs) in the dentate gyrus of rat brain slices at 34 °C. Multiple-pulse depression (MPD) was examined in trains of 5 or 10 inhibitory postsynaptic currents (IPSCs) evoked at frequencies of 10–00 Hz under several conditions that inhibit transmitter release: block of voltage-dependent Ca²⁺ channels by Cd²⁺ (10 μ m ), activation of γ-amino-butyric acid type B receptors (GABA_BRs) by baclofen (10 μ m ) and activation of muscarinic acetylcholine receptors (mAchRs) by carbachol (2 μ m ). All manipulations led to a substantial inhibition of synaptic transmission, reducing the amplitude of the first IPSC in the train (IPSC₁) by 72 %, 61 % and 29 %, respectively. However, MPD was largely preserved under these conditions (0.34 in control versus 0.31, 0.50 and 0.47 in the respective conditions at 50 Hz). Similarly, a theta burst stimulation (TBS) protocol reduced IPSC₁ by 54 %, but left MPD unchanged (0.40 in control and 0.39 during TBS). Analysis of both fractions of transmission failures and coefficients of variation (CV) of IPSC peak amplitudes suggested that MPD had a presynaptic expression site, independent of release probability. In conclusion, different types of presynaptic modulation of inhibitory synaptic transmission converge on a reduction of synaptic strength, while short-term dynamics are largely unchanged.     

Comparative studies on internalization of gold labelled mistletoe lectin I (MLI), its subunits, and of an immunotoxin into mouse L 1210V leukemia cells.

Using a preembedding electron microscopic technique, the binding and internalization of gold labelled mistletoe lectin I (MLI.Au), its 2 A subunits (MLI-A.Au) and of the B subunit (MLI-B.Au) in murine L 1210V leukemia cells was analysed. Furthermore, the endocytosis of a gold marked immunotoxin (MoAb-16-MLI-A.Au), consisting of a monoclonal antibody (MoAb-16) reacting with L 1210V cells and the cytotoxic A subunits (MLI-A) was detected. The cells were incubated with MLI.Au, MLI-A.Au, MLI-B.Au, or MoAb-16-MLI-A.Au at 37 degrees C for 1, 3, 5, 10, 20 or 30 min, respectively. Remarkable differences were found in the endocytotic pathway and internalization kinetics. The endocytosis of MLI, its subunits and of the immunotoxin has been compared to that of the other ligands in various systems.     

Viral load,CD4 percentage,and delayed-type hypersensitivity in subjects receiving the HIY-1 Immunogen and antiviral drug therapy

Two trials of subjects inoculated with the inactivated, gp120-depleted HIV-1 Immunogen are reported. In one study, in which 19 subjects received ZDV and 8 subjects received ddI, treatment with the HIV-1 Immunogen did not affect the pharmacokinetic parameters of the antiviral drugs. In another study, 65 subjects who were previously immunized with the HIV-1 Immunogen over a mean period of 4.0 years (range, 1.2–5.4 years) received inoculations at 0 and 6 months. At some point during this 48-week study, 72% of the subjects (47/65) were receiving antiviral drug therapy. The HIV-1 DNA load in CD4 cells and CD4 percentage were found to be stable over the 48-week period. Delayed-type hypersensitivity to HIV-1 antigens increased after two inoculations with the HIV-1 Immunogen. In these two trials, no serious treatment-related adverse events were documented in the subjects. The two studies presented herein are the first to suggest that an immune-based therapy such as the HIV-1 Immunogen can be combined safely with antiviral drugs, supporting further study to evaluate the clinical utility of this approach.     

Characterization of Group B Streptococcal Invasion of Human Chorion and Amnion Epithelial Cells In Vitro

Group B streptococci (GBS) have been cultured from the chorioamnionic membrane of pregnant women, usually in association with chorioamnionitis and premature labor (K. A. Boggess, D. H. Watts, S. L. Hillier, M. A. Krohn, T. J. Benedetti, and D. A. Eschenbach, Obstet. Gynecol. 87:779–784, 1996). Colonization and infection of placental membranes can be a prelude to neonatal GBS infections even in the presence of intact membranes (R. L. Naeye and E. C. Peters, Pediatrics 61:171–177, 1978), suggesting that GBS cause chorioamnionitis or establish amniotic fluid infections by partial or complete penetration of the placental membranes. We have isolated and grown cultures of primary chorion and amnion cells from human cesarean-section placentas. This has provided a biologically relevant model for investigating GBS adherence to and invasion of the two epithelial barriers of the placental membrane. GBS adhered to chorion cell monolayers to a high degree. Pretreatment of GBS with trypsin reduced adherence up to 10-fold, which suggested that the bacterial ligand(s) was a protein. GBS invaded chorion cells at a high rate in vitro, and invasion was dependent on cellular actin polymerization. GBS could be seen within intracellular vacuoles of chorion cells by transmission electron microscopy. We also demonstrated that GBS were capable of transcytosing through intact chorion cell monolayers without disruption of intracellular junctions. GBS also adhered to amnion cells; in contrast, however, these bacteria failed to invade amnion cells under a variety of assay conditions. GBS interactions with the chorion epithelial cell layer shown here correlate well with epidemiological and pathological studies of GBS chorioamnionitis. Our data also suggest that the amnion cell layer may provide an effective barrier against infection of the amniotic fluid.