Detection and characterization of betaretroviral sequences, related to sheep Jaagsiekte virus, in Africans from Nigeria and Cameroon

Jaagsiekte retrovirus (JSRV) causes ovine pulmonary adenomatosis (OPA) that resembles bronchioloalveolar carcinoma (BAC) in humans. To test the possible role of JSRV in human diseases, DNA specimens from 103 individuals either healthy or suffering from lung carcinomas were analyzed for JSRV sequences. orf-x sequences were detected in 19 of 64 samples and gag-prt sequences in 4 of 38 samples, predominantly in individuals from Africa. Sequences obtained from orf-x amplimers varied in-between each other and differed from control endogenous ovine JSRV sequence. No association with lung cancer was found. This is the first report of JSRV-like sequences detected in humans.     

转录组测序鉴定 TCF3-ZNF384阳性的急性B淋巴细胞白血病及其实验室及临床特点

目的:鉴定1例难治/复发急性B淋巴细胞白血病(acute B cell lymphoblastic leukemia, B-ALL)患者中具有病理意义的融合基因,并探讨其实验室及临床特点。方法:应用转录组测序分析可能存在的融合基因,并结合实验室检测和临床资料进行分析。结果:经鉴定患者携带 TCF3 exon...     

Removal of either N-glycan site from the envelope receptor binding domain of Moloney and Friend but not AKV mouse ecotropic gammaretroviruses alters receptor usage

Three N-linked glycosylation sites were removed from the envelope glycoproteins of Friend, Moloney, and AKV mouse ecotropic gammaretroviruses: gs1 and gs2, in the receptor binding domain; and gs8, in a region implicated in post-binding cell fusion. Mutants were tested for their ability to infect rodent cells expressing 4 CAT-1 receptor variants. Three mutants (Mo-gs1, Mo-gs2, and Fr-gs1) infect NIH 3T3 and rat XC cells, but are severely restricted in Mus dunni cells and Lec8, a Chinese hamster cell line susceptible to ecotropic virus. This restriction is reproduced in ferret cells expressing M. dunni dCAT-1, but not in cells expressing NIH 3T3 mCAT-1. Virus binding assays, pseudotype assays, and the use of glycosylation inhibitors further suggest that restriction is primarily due to receptor polymorphism and, in M. dunni cells, to glycosylation of cellular proteins. Virus envelope glycan size or type does not affect infectivity. Thus, host range variation due to N-glycan deletion is receptor variant-specific, cell-specific, virus type-specific, and glycan site-specific.     

Increased prevalence of transfusion-transmitted virus and cross-reactivity with immunodominant epitopes of the HRES-1/p28 endogenous retroviral autoantigen in patients with systemic lupus erythematosus

OBJECTIVE: Systemic lupus erythematosus (SLE) patients produce autoantibodies to HRES-1/p28, a human endogenous retrovirus-encoded nuclear protein. To identify cross-reactive viral antigens capable of triggering autoreactivity, HRES-1/p28 epitopes were mapped by SLE antibodies. METHODS: Forty-four peptides overlapping HRES-1/p28 and 13 viral peptides were synthesized on cellulose membrane and tested for recognition by antibodies from 16 HRES-1 Western blot seropositive SLE patients. Transfusion-transmitted virus (TTV) was detected by gene amplification in sera of 211 SLE patients, 78 healthy SLE family members, 199 unrelated healthy donors, and 91 rheumatoid arthritis (RA) patients. RESULTS: HRES-1/p28 residues 41-55, 121-135, and 156-170 were recognized by 12/16 (75.0%), 11/16 (68.8%), and 9/16 lupus sera (56.25%) and considered immunodominant. HRES-1/p28 residues 121-135 harbor cross-reactive epitope with retroviral peptides and the 70 K U1snRNP lupus autoantigen. HRES-1/p28 residues 41-55 and 156-170 exhibited the highest prevalence of cross-reactivity with TTV peptide ORF2a (14/16, 87%). Prevalence of TTV DNA was increased in lupus patients (120/211) with respect to healthy (66/199; P < 0.0001) or RA controls (23/91; P < 0.0001). TTV prevalence in healthy lupus relatives (40/78) was decreased with respect to lupus patients (80/121; P = 0.0184) and increased with respect to unrelated healthy donors (66/199; P = 0.0026). HRES-1/p28 Western blot reactivity was observed in 12/23 TTV PCR-negative donors and 43/58 TTV PCR-positive donors (P < 0.0281). CONCLUSIONS: Increased prevalence of TTV and molecular mimicry with HRES-1/p28 may contribute to generation of antinuclear antibodies and pathogenesis of SLE.     

Immunolocalization of leptin and its receptor in the pancreas of the horse

The aim of the present study was to demonstrate the presence and the distribution of leptin and its receptor in the pancreas of horses of both sexes by immunohistochemical techniques. The presence and the distribution of leptin receptor were also investigated in the initial portion of the duodenum, near the duodenal ampulla. The immunohistochemical investigation demonstrates the immunolocalization of both leptin and its receptor in the endocrine cells of pancreatic islets, which led us to hypothesize that leptin may possibly exert an autocrine/paracrine action on the endocrine pancreas. Examination of the exocrine pancreas in the same treated sections showed the presence of leptin-positive cells in the wall of the interlobular ducts where, however, the receptor was not found. This observation led us to consider that some cells of the ducts may perform some minimal secretory activity, and that leptin produced by these ductal cells may reach the duodenum in the pancreatic juice. This hypothesis is enhanced by the presence of leptin-receptor in the duodenum of the same animals, where the epithelial cells of the mucosa showed intense immunolocalization in the brush border. Consequently it is possible that the ductular leptin may play a regulatory role on the functionality of the enterocytes.     

Neuropeptide distributions in the colon,cecum, and jejunum of the horse

The pelvic flexure portion of the equine large colon is the proposed location of a pacemaker mechanism. This study was conducted to ascertain whether the distribution of certain putative neurotransmitters differs at the pelvic flexure compared to other sampling sites. Tissue samples were collected from the intestinal tracts of six horses. Serial sections from these samples were reacted with primary antisera specific for substance P, vasoactive intestinal polypeptide (VIP), methionine-Enkephalin, and calcitonin gene-related peptide (CGRP). The regional distribution of immunoreactive neuronal elements was uniform for each of the neuropeptides except VIP. Although neurons exhibiting VIP-like immunoreactivity were abundant throughout the colon, they were somewhat more plentiful near the apex of the pelvic flexure and the left dorsal colon. These neurons may participate in the initiation and propagation of the propulsive/retropulsive contraction waves, which emanate from this location and are believed to lend a sphincter-like capacity to the pelvic flexure. The submucosal plexus was replete with neurons with intense substance P and VIP-like reactivity. Reactive fibers left submucosal ganglia to project to the intestinal mucosa, reflecting a possible secretogogic role for these neurons. This role may be especially important for the horse as a hindgut fermenter. There were abundant methionine-Enkephalin and substance P-like reactive varicosities throughout the myenteric plexus, many of which established a pericellular plexus of varicose fibers. The abundance of these varicosities, which may correlate with a high degree of neuronal integration, did not vary regionally. These data may enhance our understanding of both normal colonic peristalsis and motility disorders caused by a depletion of these neuropeptides. © 1993 Wiley-Liss, Inc.     

Divergent and dynamic activity of endogenous retroviruses in burn patients and their inflammatory potential

Genes constitute ~ 3% of the human genome, whereas human endogenous retroviruses (HERVs) represent ~ 8%. We examined post-burn HERV expression in patients' blood cells, and the inflammatory potentials of the burn-associated HERVs were evaluated. Buffy coat cells, collected at various time points from 11 patients, were screened for the expression of eight HERV families, and we identified their divergent expression profiles depending on patient, HERV, and time point. The population of expressed HERV sequences was patient-specific, suggesting HERVs' inherent genomic polymorphisms and/or differential expression potentials depending on characteristics of patients and courses of injury response. Some HERVs were shared among the patients, while the others were divergent. Interestingly, one burn-associated HERV gag gene from a patient's genome induced IL-6, IL-1β, Ptgs-2, and iNOS. These findings demonstrate that injury stressors initiate divergent HERV responses depending on patient, HERV, and disease course and implicate HERVs as genetic elements contributing to polymorphic injury pathophysiology.     

Dynamics of the hind limb at walk in horse and dog

Summary The dynamics of the hind limbs of the horse and dog at walk are compared. The kinematics were studied by electromyography of animals walking on a moving belt, and by cinephotography in horses walking on the ground and in dogs walking on a moving belt and on the ground.This study reveals that: 1) the retraction of the hoof or foot relative to the hip at the end of the support phase is less in the horse than in the dog; 2) the change in the sense of the movements of the hind limb segments at the end of the support phase and at the beginning of the swing phase occurs earlier in the horse (55–60% of the cycle of a stride) than in the dog (70%); 3) in neither species is there activity in the retractor muscles of the hind limb at the end of the support phase, so that the push-off is effected by the dynamic effect of the load (gravity) and the elastic resilience of the retractor muscles; 4) in the horse, the cannon passes bevond the vertical and makes it necessary to bring the cranial tibial muscle into action to prevent overextension of the hock joint; in the dog, the metatarsus remains in an approximately vertical position and the superficial digital flexor muscle remains active throughout the support phase; 5) at placing, the moment ofF _I(Fig. 1) about the foot provokes a tensile strain on the plantar aspect of the tibia and a compressive strain on its dorsal aspect: the action of the gastrocnemius muscle centres the line of action of the load on the tibia in this phase; 6) at the end of the support phase, the relatively greater moment of F _Iabout the hoof of the horse makes it necessary to bring the cranial tibial muscle into action to centre the line of action of the load on to the tibia; 7) the tendinous interosseous and superficial digital flexor muscle of the horse store elastic energy at impact and use this energy to stretch the peroneus tertius tendon, the energy ultimately being used to flex the hock at lifting; the superficial digital flexor and the peroneus tertius tendons coordinate the movements of stifle and hock during the swing phases; all the components mentioned save energy: the horse is an animal built for great stamina; 8) in the dog, the analoga of the aforementioned tendons are muscular; consequently the dog is able to dig its digits and claws into the ground for a strong grip and great friction: the digitigrade dog is adapted and for great speed.