Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report three patients with intestinal microvillous dystrophy, two of whom were siblings. The relatively delayed clinical presentation and the lack of classical microvillous inclusions distinguish these cases from the previously described microvillous inclusion disease (MVID). There appears to be an underrecognized spectrum of microvillous disorders leading to fatal intractable secretory diarrhea in infants. In our three cases the diagnosis was suggested by periodic acid-Schiff (PAS) and alkaline phosphatase preparations of a jejunal biopsy specimen showing thinning or absence of brush border staining, which was confirmed by electron microscopy. The latter showed poorly developed and haphazardly arranged microvilli with intracytoplasmic vesicular bodies but no true inclusions. As in MVID, the prognosis of intestinal microvillous dystrophy is poor. The occurrence of the disease in two siblings of consanguinous parents suggests an autosomal recessive inheritance, and like MVID, genetic counselling of affected families is essential.
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PMID:Intestinal microvillous dystrophy: a variant of microvillous inclusion disease or a new entity? 767 89

Effects of acute cytomegalovirus (CMV) infections on transplantation-associated atherosclerosis (TxAA) were studied in a rat model for chronic vascular rejection. Rats underwent orthotopic abdominal allogeneic aorta transplantation. Neo-intima formation and media thinning was quantitated by measurement of cross-sectional surface areas (CSA) at day 50 post transplantation (Tx). Acute rat cytomegalovirus (RCMV) infection, established at the moment of maximum intimal proliferation and influx of inflammatory cells in the adventitia, resulted in enhanced neo-intima formation, accompanied by increased influx and proliferation of smooth muscle cells (smc) in the intima. This effect was completely inhibited by HPMPC, a very potent and selective inhibitor of CMV replication, indicating the virus specificity of the measured effects. Despite increased neointima formation, media thinning ("necrosis") was not affected by RCMV infection.
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PMID:Enhancement of transplantation-associated atherosclerosis by CMV, which can be prevented by antiviral therapy in the form of HPMPC. 1127 Dec 53

Congenital defects in the intestinal mucosa can provoke diarrhea in the neonatal period. This kind of diarrhea is difficult to treat and the outcome is bad if intestinal transplantation is not done. We describe the case of newborn female with severe protracted secretory diarrhea, which started after first oral intake of breast milk. The newborn presented with severe dehydration and persistent metabolic acidosis though potential treatment was not stopped. Endoscopy with the biopsies from the distal part of duodenum mucosa was done on the third week of life. Histological examination revealed the pathological mucosa with the total microvillous atrophy, surface epithelium thinning and histochemical PAS (Periodic acid-Schiff reaction) positivity of enterocytes apical region. These changes are typical for rare microvillous inclusion disease. When the diagnosis of microvillous inclusion disease is made, the only treatment is total parenteral nutrition and intestinal transplantation.
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PMID:Microvillous inclusion disease. 1545 73

The nuclear lamina is a major obstacle encountered by herpesvirus nucleocapsids in their passage from the nucleus to the cytoplasm (nuclear egress). We found that the human cytomegalovirus (HCMV)-encoded protein kinase UL97, which is required for efficient nuclear egress, phosphorylates the nuclear lamina component lamin A/C in vitro on sites targeted by Cdc2/cyclin-dependent kinase 1, the enzyme that is responsible for breaking down the nuclear lamina during mitosis. Quantitative mass spectrometry analyses, comparing lamin A/C isolated from cells infected with viruses either expressing or lacking UL97 activity, revealed UL97-dependent phosphorylation of lamin A/C on the serine at residue 22 (Ser(22)). Transient treatment of HCMV-infected cells with maribavir, an inhibitor of UL97 kinase activity, reduced lamin A/C phosphorylation by approximately 50%, consistent with UL97 directly phosphorylating lamin A/C during HCMV replication. Phosphorylation of lamin A/C during viral replication was accompanied by changes in the shape of the nucleus, as well as thinning, invaginations, and discrete breaks in the nuclear lamina, all of which required UL97 activity. As Ser(22) is a phosphorylation site of particularly strong relevance for lamin A/C disassembly, our data support a model wherein viral mimicry of a mitotic host cell kinase activity promotes nuclear egress while accommodating viral arrest of the cell cycle.
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PMID:Viral mimicry of Cdc2/cyclin-dependent kinase 1 mediates disruption of nuclear lamina during human cytomegalovirus nuclear egress. 1916 38

Antibodies reactive with the ovarian glycoprotein zona pellucida (ZP) have been linked with human female infertility. Anti-fertility vaccines that target ZP antigens have been utilized to restrict pest animal populations and their efficacy is associated with ovary-specific antibody induction. However, the necessity for zona pellucida-specific antibody in mediating infertility has not been examined in vivo. A recombinant mouse cytomegalovirus vaccine encoding murine zona pellucida 3 that induces rapid and complete infertility in BALB/c mice has been produced. The onset of infertility is temporally related to the presence of antibody sequestered into ovarian follicles and binding to the ZP of infected mice and the loss of mature follicles. When this vaccine was inoculated into immunoglobulin-deficient BALB/c mice with a null mutation in the immunoglobulin mu chain gene Igh-6, fertility was unaffected. Passive transfer of serum containing ZP3 antibodies also elicited transient infertility. Electron microscopy of ovarian tissue collected from ZP3-immunized immunocompetent mice demonstrated significant focal thinning of the zona pellucida (ZP) with reduced length and concentration of transzonal processes and many oocytes displayed evidence of injury. None of these changes were found in vaccinated immunoglobulin-deficient mice. These data confirm that ZP3-reactive antibody is necessary and sufficient to induce autoimmune-mediated follicular depletion and fertility suppression following the inoculation of this vaccine, and suggest that this is due to impaired zona pellucida formation. These findings have relevance in understanding the etiology of autoimmune ovarian disease in woman where anti-ZP antibodies are likely to have a causal role in infertility.
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PMID:Immunoglobulin to zona pellucida 3 mediates ovarian damage and infertility after contraceptive vaccination in mice. 2038 3

The identification of >100 genes causing inherited retinal degeneration and the promising results of recent gene augmentation trials have led to an increase in the number of studies investigating the preclinical efficacy of viral-mediated gene transfer. Despite success using adeno-associated viruses, many disease-causing genes, such as ABCA4 or USH2A, are too large to fit into these vectors. One option for large gene delivery is the family of integration-deficient helper-dependent adenoviruses (HDAds), which efficiently transduce postmitotic neurons. However, HDAds have been shown in other organ systems to elicit an immune response, and the immunogenicity of HDAds in the retina has not been characterized. In this study, HDAd serotype 5 (HDAd5) was found to successfully transduce rod and cone photoreceptors in ex vivo human retinal organ cultures. The ocular inflammatory response to subretinal injection of the HDAd5 was evaluated using a rat model. Subretinal injection of HDAd5 carrying cytomegalovirus promoter-driven enhanced green fluorescent protein (HDAd5-CMVp-eGFP) elicited a robust inflammatory response by 3 days postinjection. This reaction included vitreous infiltration of ionized calcium-binding adapter molecule 1 (Iba1)-positive monocytes and increased expression of the proinflammatory protein, intercellular adhesion molecule 1 (ICAM-1). By 7 days postinjection, most Iba1-positive infiltrates migrated into the neural retina and ICAM-1 expression was significantly increased compared with buffer-injected control eyes. At 14 days postinjection, Iba1-positive cells persisted in the retinas of HDAd5-injected eyes, and there was thinning of the outer nuclear layer. Subretinal injection of an empty HDAd5 virus was used to confirm that the inflammatory response was in response to the HDAd5 vector and not due to eGFP-induced overexpression cytotoxicity. Subretinal injection of lower doses of HDAd5 dampened the inflammatory response, but also eGFP expression. Despite their larger carrying capacity, further work is needed to elucidate the inflammatory pathways involved and to identify an immunomodulation paradigm sufficient for safe and effective transfer of large genes to the retina using HDAd5.
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PMID:Helper-Dependent Adenovirus Transduces the Human and Rat Retina but Elicits an Inflammatory Reaction When Delivered Subretinally in Rats. 3145 26

Gastrointestinal graft-versus-host disease (GVHD) is a common complication after hematopoietic stem cell transplantation. Concomitant cytomegalovirus (CMV) enteritis worsens the prognosis of this condition. We report a case of small bowel perforation associated with gastrointestinal GVHD and CMV enteritis in a patient with leukemia who was successfully treated surgically. A 39-year-old man presented with intestinal perforation necessitating emergency surgical intervention. He was diagnosed with T-cell acute lymphoblastic leukemia and developed severe gastrointestinal GVHD and CMV enteritis after hematopoietic stem cell transplantation. His terminal ileum showed a perforation with diffuse wall thinning, and petechiae were observed over long segments of the distal ileum and the proximal colon. Small bowel segmental resection and a subtotal colectomy with a double-barreled ileocolostomy were performed. The patient recovered uneventfully after the operation. Based on reports described in the literature, surgery plays a minor role in the management of gastrointestinal GVHD; however, timely surgical intervention could be effective in selected patients.
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PMID:Small Bowel Perforation Associated With Gastrointestinal Graft-Versus-Host Disease and Cytomegalovirus Enteritis in a Patient With Leukemia: A Case Report With Literature Review. 3291 38