Medical Sciences Commons^™

Identifying Global Anatomical Differences: Deformation-Based Morphometry, J Ashburner, C Hutton, R Frackowiak, Ingrid Johnsrude, C Price, K Friston

Brain and Mind Institute Researchers' Publications

The aim of this paper is to illustrate a method for identifying macroscopic anatomical differences among the brains of different populations of subjects. The method involves spatially normalizing the structural MR images of a number of subjects so that they all conform to the same stereotactic space. Multivariate statistics are then applied to the parameters describing the estimated nonlinear deformations that ensue. To illustrate the method, we compared the gross morphometry of male and female subjects. We also assessed brain asymmetry, the effect of handedness, and interactions among these effects.

Stent Placement Compared With Balloon Angioplasty For Obstructed Coronary Bypass Grafts. Saphenous Vein De Novo Trial Investigators., M P Savage, J S Douglas, D L Fischman, C J Pepine, S B King, J A Werner, S R Bailey, P A Overlie, S H Fenton, J A Brinker, M B Leon, S Goldberg

Department of Medicine Faculty Papers

BACKGROUND: Treatment of stenosis in saphenous-vein grafts after coronary-artery bypass surgery is a difficult challenge. The purpose of this study was to compare the effects of stent placement with those of balloon angioplasty on clinical and angiographic outcomes in patients with obstructive disease of saphenous-vein grafts.

METHODS: A total of 220 patients with new lesions in aortocoronary-venous bypass grafts were randomly assigned to placement of Palmaz-Schatz stents or standard balloon angioplasty. Coronary angiography was performed during the index procedure and six months later.

RESULTS: As compared with the patients assigned to angioplasty, those assigned to stenting had a higher rate …

Cellular Basis Of Decreased Immune Responses To Pneumococcal Vaccines In Aged Mice, Manju Garg, Wei Luo, Alan M. Kaplan, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Previously, model systems were developed in our laboratory to study murine immune responses to the 23-valent pneumococcal polysaccharide vaccine Pnu-Imune, both in vivo and in vitro (M. Garg and B. Subbarao, Infect. Immun. 60:2329-2336, 1992; M. Garg, A. M. Kaplan, and S. Bondada, J. Immunol. 152: 1589-1596, 1994). Using these systems, we found that aged mice did not respond to the vaccine in vivo or in vitro. Cell separation studies showed that the unresponsiveness of the aged spleen cells to the vaccine was not due to an intrinsic B-cell defect or to T-cell-mediated immunosuppression but resulted from an accessory cell …

Disruption Of The Cbfa2 Gene Causes Necrosis And Hemorrhaging In The Central Nervous System And Blocks Definitive Hematopoiesis., Qing Wang, Terryl Stacy, Michael M Binder, Miguel Marin-Padilla, Arlene H. Sharpe, Nancy A. Speck

Dartmouth Scholarship

The CBFA2 (AML1) gene encodes a DNA-binding subunit of the heterodimeric core-binding factor. The CBFA2 gene is disrupted by the (8;21), (3;21), and (12;21) chromosomal translocations associated with leukemias and myelodysplasias in humans. Mice lacking a CBF alpha 2 protein capable of binding DNA die between embryonic days 11.5 and 12.5 due to hemorrhaging in the central nervous system (CNS), at the nerve/CNS interfaces of cranial and spinal nerves, and in somitic/intersomitic regions along the presumptive spinal cord. Hemorrhaging is preceded by symmetric, bilateral necrosis in these regions. Definitive erythropoiesis and myelopoiesis do not occur in Cbfa2-deficient embryos, and disruption …

Cd40-Cd40 Ligand Interactions In Experimental Allergic Encephalomyelitis And Multiple Sclerosis., Koen Gerritse, Jon D. Laman, Randolph J. Noelle, Alejandro Aruffo

Dartmouth Scholarship

We investigated the role of CD40-CD40 ligand (CD40L) interactions in multiple sclerosis (MS) and experimental allergic encephalomyelitis (EAE). Activated helper T cells expressing CD40L (gp39) surface protein were found in MS patient brain sections, but not in brain tissue sections of normal controls or patients with other neurological disease. CD40L-positive cells were co-localized with CD40-bearing cells in active lesions (perivascular infiltrates). Most of these CD40-bearing cells proved to be of the monocytic lineage (macrophages or microglial cells), and relatively few were B cells. To functionally evaluate CD40-CD40L interactions, EAE was elicited in mice by means of proteolipid-peptide immunization. Treatment with …

Analysis Of The Effects Of Overexpression Of Metallothionein-I In Transgenic Mice On The Reproductive Toxicology Of Cadmium., T Dalton, Kai Fu, G C Enders, R D Palmiter, G K Andrews

Journal Articles: Pathology and Microbiology

Exposure to low levels of cadmium reduces fertility. In male mice spermatogenesis is highly sensitive to cadmium, whereas in females the peri-implantation period of pregnancy is sensitive. To examine the potential roles of the cadmium-binding protein, metallothionein (MT), in the reproductive toxicology of cadmium, we examined a transgenic mouse strain that overexpresses metallothionein-I (MT-I). These mice had dramatically increased steady-state levels of MT-I mRNA and MT in the testes and in the female reproductive tract during the peri-implantation period of pregnancy, and this overexpression occurred in a cell-specific and temporally regulated manner similar to that of the endogenous MT-I gene. …

A Requirement For Bone Morphogenetic Protein-7 During Development Of The Mammalian Kidney And Eye., Andrew T. Dudley, K. M. Lyons, E. J. Robertson

Journal Articles: Genetics, Cell Biology & Anatomy

BMP-7/OP-1, a member of the transforming growth factor-beta (TGF-beta) family of secreted growth factors, is expressed during mouse embryogenesis in a pattern suggesting potential roles in a variety of inductive tissue interactions. The present study demonstrates that mice lacking BMP-7 display severe defects confined to the developing kidney and eye. Surprisingly, the early inductive tissue interactions responsible for establishing both organs appear largely unaffected. However, the absence of BMP-7 disrupts the subsequent cellular interactions required for their continued growth and development. Consequently, homozygous mutant animals exhibit renal dysplasia and anophthalmia at birth. Overall, these findings identify BMP-7 as an essential …

A Randomized Comparison Of Coronary-Stent Placement And Balloon Angioplasty In The Treatment Of Coronary Artery Disease. Stent Restenosis Study Investigators., David L. Fischman, Martin B. Leon, Donald S. Baim, Richard A. Schatz, Michael P. Savage, Ian Penn, Katherine Detre, Lisa Veltri, Donald Ricci, Masakiyo Nobuyoshi, Michael Cleman, Richard Heuser, David Almond, Paul S. Teirstein, R. David Fish, Antonio Colombo, Jeffrey Brinker, Jeffrey Moses, Alex Shaknovich, John Hirshfeld, Stephen Bailey, Stephen Ellis, Randal Rake, Sheldon Goldberg

Department of Medicine Faculty Papers

BACKGROUND: Coronary-stent placement is a new technique in which a balloon-expandable, stainless-steel, slotted tube is implanted at the site of a coronary stenosis. The purpose of this study was to compare the effects of stent placement and standard balloon angioplasty on angiographically detected restenosis and clinical outcomes.

METHODS: We randomly assigned 410 patients with symptomatic coronary disease to elective placement of a Palmaz-Schatz stent or to standard balloon angioplasty. Coronary angiography was performed at base line, immediately after the procedure, and six months later.

RESULTS: The patients who underwent stenting had a higher rate of procedural success than those who …

Reversal Of Age-Associated Decline In Immune Response To Pnu-Imune Vaccine By Supplementation With The Steroid Hormone Dehydroepiandrosterone, Manju Garg, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Recently, we reported that murine antibody responses to the 23-valent pneumococcal polysaccharide (Pnu-Imune) vaccine declined with age. Here we present data to support the concept that age-associated immune defects are not only due to intrinsic defects in immune cells but are also due to extrinsic factors emanating from the neuroendocrine system. We found that supplementation with dehydroepiandrosterone, a steroid hormone known to be reduced in the aged, corrects the immune deficiency of aged mice and significantly enhanced their splenic immune responses to the Pnu-Imune vaccine.

Immune Responses Of Systemic And Mucosal Lymphoid Organs To Pnu-Imune Vaccine As A Function Of Age And The Efficacy Of Monophosphoryl Lipid A As An Adjuvant, Manju Garg, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

A murine model system was established to study immune responses to the Pnu-Imune vaccine, which is made up of 23 different pneumococcal capsular polysaccharides. In this animal model, antibody-forming cell responses to 21 of 23 individual polysaccharides in the vaccine were detected. The Pnu-Imune vaccine elicited good antibody responses from the spleens and mesenteric lymph nodes (MLN) of young mice, whereas a variety of other peripheral lymph nodes were unresponsive. The immunoglobulin M plaque-forming cell (PFC) response in the spleen to the Pnu-Imune vaccine (given intraperitoneally or subcutaneously) decreased dramatically with increasing age. However, the spleen and MLN differed in …

Maternal-Neonatal Serum Vitamin A Concentrations., Girish S. Shirali, D G. Oelberg, K P. Mehta

Manuscripts, Articles, Book Chapters and Other Papers

Prevention of neonatal vitamin A deficiency is related to the adequacy of maternal vitamin A stores. In this study we investigated maternal and cord serum vitamin A and retinol-binding protein (RBP) values in an Indian population including, for the first time, clinically vitamin A-deficient mothers. Twenty-eight maternal-neonatal pairs were selected from maternal cohorts of high socioeconomic status without clinical evidence of vitamin A deficiency (group I) and low socioeconomic status with conjunctival xerosis and Bitot's spots (group II). Maternal education, caloric and vitamin A intakes, weight, height, hemoglobin, and birth weight were significantly lower in group II. Serum vitamin A …

Parentage Analysis With Genetic Markers In Natural Populations I The Expected Proportion Of Offspring With Unambiguous Paternity, R Chakraborty, T R Meagher, P E Smouse

Faculty, Staff and Student Publications

Recent studies indicate that polymorphic genetic markers are potentially helpful in resolving genealogical relationships among individuals in a natural population. Genetic data provide opportunities for paternity exclusion when genotypic incompatibilities are observed among individuals, and the present investigation examines the resolving power of genetic markers in unambiguous positive determination of paternity. Under the assumption that the mother for each offspring in a population is unambiguously known, an analytical expression for the fraction of males excluded from paternity is derived for the case where males and females may be derived from two different gene pools. This theoretical formulation can also be …

Psammoma Bodies In Neuroendocrine Carcinoma Of The Uterine Cervix., V L. Russin, Philip T. Valente, P Hanjani

Department of Pathology & Laboratory Medicine

No abstract provided.

An Experimental Study Of The Longest Tolerable Time Of The Total Portal Triad Occlusion In Normothermia In Rabbit, X P Chen, Z D Wu

Faculty, Staff and Student Publications

No abstract provided.

Genetics And Epidemiology Of Gallbladder Disease In New World Native Peoples, K M Weiss, R E Ferrell, C L Hanis, P N Styne

Faculty, Staff and Student Publications

Native peoples of the New World, including Amerindians and admixed Latin Americans such as Mexican-Americans, are highly susceptible to diseases of the gallbladder. These include cholesterol cholelithiasis (gallstones) and its complications, as well as cancer of the gallbladder. Although there is clearly some necessary dietary or other environmental risk factor involved, the pattern of disease prevalence is geographically associated with the distribution of genes of aboriginal Amerindian origin, and levels of risk generally correspond to the degree of Amerindian admixture. This pattern differs from that generally associated with Westernization, which suggests a gene-environment interaction, and that within an admixed population …

Genetically Controlled Variation Of “Acid” Beta-Galactosidase Detected In Rattus Norvegicus By Isoelectric Focusing, T C Douglas, K A Kimmel, P E Dawson

Faculty, Staff and Student Publications

Two genetically variant forms of rat "acid" beta-galactosidase were found to differ in isoelectric point and pH dependence, but not in thermostability or sensitivity to inhibition by p-mercuribenzoate (PMB). The results of two backcrosses and an intercross indicated that the isoelectric focusing phenotypes are controlled by two codominant alleles at a single autosomal locus, for which we propose the name Glb-1. No significant linkage between Glb-1 and albino (LG I), brown (LG II), or hooded (LG VI) was observed. Strain-specific differences in total levels of kidney beta-galactosidase were detected, but it is not yet known whether the variation is controlled …

Three Linked Enzyme Loci In Fishes: Implications In The Evolution Of Vertebrate Chromosomes, D C Morizot, D A Wright, M J Siciliano

Faculty, Staff and Student Publications

A three-point linkage group comprised of loci coding for adenosine deaminase (ADA), glucose-6-phosphate dehydrogenase (G6PDH), and 6-phospho-gluconate dehydrogenase (6PGD) is described in fish of the genus Xiphophorus (Poeciliidae). The alleles at loci in this group were shown to assort independently from the alleles at three other loci--isocitrate dehydrogenase 1 and 2, and glyceraldehyde-3-phosphate dehydrogenase 1. Alleles at the latter three loci also assort independently from each other. Data were obtained by observing the segregation of electrophoretically variant alleles in reciprocal backcross hybrids derived from crosses between either X. helleri guentheri or X. h. strigatus and X. maculatus. The linkage component …

The Parenchymal Cells Of The Rat Pineal Gland, E Tapp, M Blumfield

Faculty, Staff and Students Publications

Background: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare hematologic disorder with improved survival due to advancements in treatment. However, long-term cardiovascular morbidity and mortality remain significant. Established cardiovascular risk calculators, such as the 2008 Framingham Heart Study (FHS) global cardiovascular disease (CVD) and the American College of Cardiology/American Heart Association (ACC/AHA) atherosclerotic CVD (ASCVD) risk estimators, may not adequately account for the elevated and unique cardiovascular risks in iTTP survivors.

Objectives: To evaluate the discrimination and calibration of the ACC/AHA ASCVD and FHS global CVD models in predicting major adverse cardiovascular events (MACEs) among iTTP survivors.

Methods: This retrospective …