Susceptible Organs Research Articles

Comparison of operator radiation exposure between C-arm and O-arm fluoroscopy for orthopaedic surgery

The O-arm system has recently been introduced and has the capability of combined two-dimensional (2-D) fluoroscopy imaging and three-dimensional computed tomography imaging. In this study, an orthopaedic surgical procedure using C-arm and O-arm systems in their 2-D fluoroscopy modes was simulated and the radiation doses to susceptible organs to which operators can be exposed were investigated. The experiments were performed in four configurations of the location of the X-ray source and detector. Shielding effects on the thyroid surface and the direct exposure delivered to the surgeon's hands were also compared. The results obtained show that the O-arm delivered higher doses to the sensitive organs of the operator in all configurations. The thyroid shield cut-off 89 % of the dose in the posteroanterior configuration of both imaging systems. Thus, the operators need to pay more attention to managing radiation exposure, especially when using the O-arm system.

Human anti-microbial cathelicidin peptide LL-37 suppresses the LPS-induced apoptosis of endothelial cells

Sepsis is a systemic disease resulting from harmful host response to bacterial infections. During the exacerbation of severe sepsis or septic shock, apoptosis of endothelial cells is induced in susceptible organs such as the lung and liver and triggers microcirculatory disorder and organ dysfunction. LPS, an outer membrane component of Gram-negative bacteria, is one of the major virulence factors for the pathogenesis. We previously reported that LL-37, a human anti-microbial cathelicidin peptide, potently neutralizes the biological activity of LPS and protects mice from lethal endotoxin shock. However, the effect of LL-37 on the LPS-induced endothelial cell apoptosis remains to be clarified. In this study, to further elucidate the action of LL-37 on severe sepsis/endotoxin shock, we investigated the effects of LL-37 on the LPS-induced endothelial cell apoptosis in vitro and in vivo using lung-derived normal human microvascular blood vessel endothelial cells (HMVEC-LBls) and D-galactosamine hydrochloride (D-GalN)-sensitized murine endotoxin shock model. LL-37 suppressed the LPS-induced apoptosis of HMVEC-LBls. In addition, LL-37 inhibited the binding of LPS possibly to the LPS receptors (CD14 and toll-like receptor 4) expressed on the cells. Thus, LL-37 can suppress the LPS-induced apoptosis of HMVEC-LBls via the inhibition of LPS binding to the cells. Furthermore, LL-37 drastically suppressed the apoptosis of hepatic endothelial cells as well as hepatocytes in the liver of murine endotoxin shock model. Together, these observations suggest that LL-37 could suppress the LPS-induced apoptosis of endothelial cells, thereby attenuating lethal sepsis/endotoxin shock.

Toxicological Pathology in the Rat Placenta

The placenta grows rapidly for a short period with high blood flow during pregnancy and has multifaceted functions, such as its barrier function, nutritional transport, drug metabolizing activity and endocrine action. Consequently, the placenta is a highly susceptible target organ for drug- or chemical-induced adverse effects, and many placenta-toxic agents have been reported. However, histopathological examination of the placenta is not generally performed, and the placental toxicity index is only the placental weight change in rat reproductive toxicity studies. The placental cells originate from the trophectoderm of the embryo and the endometrium of the dam, proliferate and differentiate into a variety of tissues with interaction each other according to the development sequence, resulting in formation of a placenta. Therefore, drug- or chemical-induced placental lesions show various histopathological features depending on the toxicants and the exposure period, and the pathogenesis of placental toxicity is complicated. Placental weight assessment appears not to be enough to evaluate placental toxicity, and reproductive toxicity studies should pay more attention to histopathological evaluation of placental tissue. The detailed histopathological approaches to investigation of the pathogenesis of placental toxicity are considered to provide an important tool for understanding the mechanism of teratogenicity and developmental toxicity with embryo lethality, and could benefit reproductive toxicity studies.

316 Peripheral Vascular Autoregulation During Ductal Closure

Background Aims: Tissue blood flow reflects the balance between perfusion pressure and local vascular resistance. The body must balance local needs against needs of central organs considered more critical. When perfusion is disrupted (eg PDA) fine control must be accomplished by variations in relative vascular resistance (RVR). We looked at serial RVR changes in the anterior cerebral artery, superior mesenteric artery and right renal artery in infants being treated for PDA. Design Methods: RVR was calculated as mean systemic blood pressure divided by mean local blood flow velocity. Flow velocities were studied by Doppler ultrasonography in 57 preterm neonates < 1750 gm. before, during and after treatment for ductal closure. All of the infants were NPO during treatment. Results: RVR [Baseline, 24 hr, 48hr] Cerebral 2.7+1.1, 3.6+1.4*, 3.9+1.5* Renal 2.2 [1.3,3.7], 2.8 [2.3, 4.1]*, 2.7 [1.7,4.1] Mesenteric 2.8 [1.8,4.3], 3.0 [2.0,4.1], 3.1 [1.8,4.5]* p< 0.05 as compared with baseline Conclusions: RVR reflects the balance of systemic vs.local flow, the essence of autoregulation. Dcreased RVR could represent a physiologic attempt to improve organ perfusion during hypotension, while increased RVR might reflect an attempt to protect susceptible organs against hypertension. To preserve blood flow, RVR would be expected to decrease in vasculature compromised by ductal shunting. Conversely, with ductal closure, increased RVR would be expected. We observed this expected response most significantly in the cerebral vasculature, implying, that this vasculature most adept at autoregulation. The mesenteric vasculature showed no autoregulatory response, which may shed further light on the association between NEC and PDA.

Ingested Shiga Toxin 2 (Stx2) Causes Histopathological Changes in Kidney, Spleen, and Thymus Tissues and Mortality in Mice

The Shiga toxin (Stx)-producing bacterial strain, Escherichia coli O157:H7, colonizes the distal small intestine and the colon, initiating serious illness, including hemolytic-uremic syndrome (HUS), characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. Although intravenous administration of purified Stx to primates has been able to reproduce the features of HUS, it has not been conclusively established as to whether ingestion of Stx alone without the bacterium poses a potential health risk. To help answer this question, in this study, we fed Shiga toxin 2 (Stx2) directly into the stomachs of mice via gavage. Our data show that ingestion of Stx2 at a concentration of 50 μg/mouse induces weight loss and kills the mice at 3-5 days post-gavage. Additional studies revealed that the toxin retains activity at low pH, that its activity is neutralized by treatment with toxin-specific antibody, and that about 1% of the fed toxin is absorbed into the blood circulation. Lethality by intraperitoneal (IP) injection of Stx2 occurred at much lower doses than by ingestion. Detailed histopathological evaluation of stained tissues by light microscopy revealed severe histopathological changes in kidneys, spleen, and thymus but not in the pancreas, lymph nodes, heart, lungs, trachea, esophagus, stomach, duodenum, jejunum, ileum, cecum, and colon. The pathological changes in the kidney appeared similar to those seen in humans with HUS. The cited data suggest that (a) most but not all of the toxin is inactivated in the digestive tract, (b) part of the oral-ingested toxin is absorbed from the digestive tract into the circulation, (c) enough active toxin reaches susceptible organs to induce damage, and (d) Stx2 in the absence of toxin-producing bacteria can be harmful to mice. The results are clinically relevant for food safety because we also found that heat treatments (pasteurization) that destroy bacteria did not inactivate the heat-resistant toxin produced and secreted by the bacteria.

Cowden syndrome and reconstructive breast surgery: Case reports and review of the literature

Cowden syndrome (CS) is a rare, autosomal dominant inherited disorder associated with multiple benign and malignant neoplasms, including breast cancer. Prophylactic resection of susceptible organs remains controversial. We briefly describe the syndrome and review management of the risk of CS-associated malignancies. Three cases of bilateral risk-reducing mastectomy and immediate breast reconstruction are described.

Effects of antibodies induced by a conjugate vaccine on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone absorptive transport, metabolism, and proliferation of human lung cells

One of the most abundant and potent lung carcinogen is the nicotine-derived tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). The monoclonal antibody P9D5 induced with a NNK-conjugate vaccine was used to investigate the ability of NNK-specific antibodies to modulate NNK-induced adverse effects as well as its absorptive transport and metabolism in two lung cancer cell lines (Calu-3 and NCI-H82). Transport experiments in Calu-3 cells with a 50-fold molar excess of apical P9D5 increased the recovery of coadministered apical NNK, with a concomitant decrease in NNK transepithelial transport of more than 50% compared to controls. In contrast, basolateral P9D5 did neither influence transepithelial transport of NNK nor its disappearance from the apical compartment. Calu-3 cells were also found to reduce NNK to NNAL and a 65-fold molar excess of NNK-specific antibody inhibited this metabolic conversion by 46 and 54% compared to irrelevant control antibody after 48 and 72 hr, respectively. The biological relevance of NNK redistribution by antibody was demonstrated by reversion of NNK-induced cell proliferation in NCI-H82 cells. Repartitioning of tobacco carcinogens by antibody may reduce their early effective peak concentrations in susceptible target organs and thus relieve overloaded local DNA repair mechanisms and diminish carcinogen-induced cell proliferation. These in vitro data therefore suggest that a prophylactic antibody response may be associated with a reduced risk of cancer.

Lessons from the aprotinin saga: current perspective on antifibrinolytic therapy in cardiac surgery

Antifibrinolytic agents have been prophylactically administered to patients undergoing cardiopulmonary bypass (CPB) to reduce postoperative bleeding due to plasmin-mediated coagulation disturbances. After the recent market withdrawal of aprotinin, a potent bovine-derived plasmin inhibitor, two lysine analogs, epsilon-aminocaproic acid and tranexamic acid are currently available for clinical use. Although the use of aprotinin recently raised major concerns about postoperative thrombosis and organ dysfunctions, there is a paucity of information on the potential complications related to lysine analogs. Using the available preclinical and clinical data, we present current perspectives on the hemostatic mechanism and potential harms of antifbirnolytic therapy related to cardiac surgery. Fibrin formation is the critical step for hemostasis at the site of vascular injury, and localized fibrinolytic activity counterbalances excess fibrin formation which might result in vascular occlusion. Inhibition of the endogenous fibrinolytic system may be associated with thrombotic complications in susceptible organs. It is thus important to understand CPB-related changes in endogenous fibrinolytic proteins (e.g., tissue plasminogen activator (tPA), plasminogen) and antifibrinolytic proteins (e.g., alpha(2)-antiplasmin).

Delayed gastric emptying and disruption of the interstitial cells of Cajal network after gastric ischaemia and reperfusion

Gastrointestinal tract is one of the most susceptible organ systems to ischaemia. Not only mucosal injury but also alterations of the intestinal motility and loss of interstitial cells of Cajal (ICC) have been reported in response to ischaemia and reperfusion (I/R). However, there are few reports on the changes in the gastric motility after gastric I/R. The present study was designed to investigate the alterations in gastric emptying, the ICC and enteric nerves that regulate smooth muscle function in response to gastric I/R. Seven-week-old male Wistar rats were exposed to gastric I/R, and the gastric emptying rates at 12 and 48 h after I/R were evaluated by the phenol red method. Expressions of gene product of c-kit receptor tyrosine kinase (c-Kit), a marker of ICC, and of neuronal proteins were also examined. Gastric emptying was transiently delayed at 12 h after I/R, but returned to normal by 48 h. Expression of c-Kit protein as assessed by Western blotting and immunofluorescent staining of the smooth muscle layer, as well as expression of the mRNA of stem cell factor, the ligand for c-Kit, were reduced at both 12 and 48 h after I/R. The expression of neuronal nitric oxide synthase (nNOS) protein as assessed by Western blotting and immunofluorescent staining was also decreased at 12 h after I/R, but was restored to normal by 48 h. Gastric I/R evokes transient gastroparesis with delayed gastric emptying, associated with disruption of the ICC network and nNOS-positive neurons.

Beyond the Knudson’s hypothesis in von Hippel–Lindau (VHL) disease—proposing vitronectin as a “gene modifier”

Von Hippel–Lindau (VHL) disease is an autosomal dominant hereditary cancer syndrome with a prevalence of 1 in 39,000 live births that results from a germline mutation of the VHL gene with over 90% penetrance by 65 years of age despite variable expression [1, 2]. VHL is a tumor suppressor gene located on the short arm of the chromosome 3 (3p25–26) that is made of three exons and widely expressed in both fetal and adult tissues [3, 4]. A patient with heritable VHL disease inherits a germline mutation of the gene from the affected parent and a normal gene from the unaffected parent (wild type). The Knudson’s two-hit hypothesis of tumorigenesis applies to the initiation of the tumor growth when a somatic mutation affects the wildtype VHL allele [5]. Although germline VHL mutations are present in all the cells of the affected individuals who inherit the genetic trait, only the cells that are somatically mutated in the wild-type gene and are parts of a susceptible organ experience tumor growth [2]. In fact, patients with VHL disease are predisposed to develop specific central nervous system (CNS) and visceral lesions [1, 2, 4]. Affected individuals may develop retinal hemangioblastomas, endolymphatic sac tumors (ELST) of the labyrinth, or craniospinal hemangioblastomas in the cerebellum, brainstem, or spinal cord [2]. Furthermore, visceral involvement in some patients affects the kidney with renal cell carcinoma (RCC) or cysts, the adrenal glands with pheochromocytomas, the pancreas with tumors or cysts, and the epididymus or the broad ligament with cystoadenomas [2]. Clinical criteria or genetic tests help in diagnosing VHL disease [1]. Obviously, patients with a family history of VHL and CNS lesions (hemangioblastomas), RCC, pheochromocytoma, pancreatic cysts or ELST will meet the criteria for diagnosis of VHL [1]. However, 20% of patients lack a family history, but meet the criteria for VHL, if they present two or more CNS hemangioblastomas, or one CNS hemangioblastoma and a visceral VHL-associated tumor [1]. A classification of the VHL disease in type 1 or 2A–C based on the VHL mutation, molecular defect, and clinical manifestations have been proposed [4]. Patients at high risk undergo testing for germline VHL mutations with 100% detection rate if they have a positive family history [1, 6]. On the contrary, patients with negative family history present with tissue mosaicism that may hamper the use of testing their peripheral blood leukocytes lacking the VHL mutation [7]. The somatic VHL mutations are present in approximately 50% of sporadic RCC, whereas 20% of cases present hypermethylated VHL gene in the same group of tumors [4]. Hypermethylation of the VHL gene has only been described in the RCC, while somatic mutations account for 30% of sporadic hemangioblastomas without any description of VHL gene hypermethylation in this group of tumors [4]. In the context of sporadic tumors, the two-hit model occurs exclusively somatically rather than in the germline [4]. The VHL gene is widely expressed in tissues, including the ones not affected by VHL-transformed phenotype. The VHL mRNA encodes a 213 amino acid residue-protein (pVHL) with an apparent molecular weight of ~24 to 30 kDa (VHL30) [1, 4]. A second pVHL isoform of approximately 19 kDa (VHL19) is the by-product of inframe start codon (ATG) at codon 54 [4]. Both isoforms have tumor suppressor activity. pVHL shuttles between the nucleus and the cytoplasm, and the nuclear-cytoplasmic trafficking is required for the function of the VHL tumor suppressor protein [4]. Primarily, pVHL complexes with J Mol Med (2009) 87:591–593 DOI 10.1007/s00109-009-0466-z

Bβ15-42 (FX06) reduces pulmonary, myocardial, liver, and small intestine damage in a pig model of hemorrhagic shock and reperfusion*

The fibrin-derived peptide Bbeta15-42 (also called FX06) has been shown to reduce myocardial infarct size following ischemia/reperfusion. Hemorrhagic shock (HS) followed by volume resuscitation represents a similar scenario, whereby a whole organism is vulnerable to reperfusion injury. We subjected male farm-bred landrace pigs ( approximately 30 kg) to HS by withdrawing blood to a mean arterial pressure of 40 mm Hg for 60 minutes. Pigs were then resuscitated with shed blood and crystalloids for 60 minutes, and at this time, FX06 (2.4 mg/kg, n = 8) or vehicle control (phosphate buffered saline; 2.4 mg/kg, n = 7) was injected as an intravenous bolus. University hospital laboratory. Anesthetized male farm-bred landrace pigs. Data are presented as mean +/- sd. Five hours after resuscitation, controls presented acute lung injury (Pao2/Fio2-ratio <300 mm Hg; extra-vascular lung water index (marker for lung injury): 9.0 +/- 1.8 mL/kg) and myocardial dysfunction/damage (cardiac index: 4.3 +/- 0.25 L/min/m; stroke volume index: 30 +/- 6 mL/m; cardiac TnT levels: 0.58 +/- 0.25 ng/mL). In contrast, FX06-treated animals showed significantly improved pulmonary and circulatory function (Pao2/Fio2-ratio >*400 mm Hg; extra-vascular lung water index: *5.2 +/- 2.1 mL/kg, cardiac index: *6.3 +/- 1.4 L/min/m; stroke volume index: *51 +/- 11 mL/m; cardiac TnT levels: *0.11 +/- 0.09 ng/mL; *p < 0.05). Also, tissue oxygenation (tpO2; mm Hg) was significantly improved during reperfusion in FX06-treated pigs when compared with controls (liver 51 +/- 4 vs. *65 +/- 4; serosa 44 +/- 5 vs. *55 +/- 7; mucosa 14 +/- 4 vs. *26 +/- 4). Finally, FX06 reduced accumulation of myeloperoxidase-positive cells (mainly neutrophils) in myocardium, liver, and small intestine and reduced interleukin-6 plasma levels (*p < 0.05; compared with controls). We conclude that in a pig model of HS and reperfusion, administration of FX06 during reperfusion protects shock- susceptible organs such as heart, lung, liver, and small intestine.

Effect of sub-acute exposure to TiO2 nanoparticles on oxidative stress and histopathological changes in Juvenile Carp (Cyprinus carpio)

Increasing application of nanotechnology highlights the need to clarify and understand nanotoxicity. Mammalian and in vitro studies have raised concerns about the toxicity of titanium dioxide nanoparticles (TiO2-NPs), but there are limited data on ecotoxicity to aquatic organisms. In this work, the sub-acute toxicity of TiO2-NPs to carp (Cyprinus carpio) was assessed. Superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD) activities and lipid peroxidation (LPO) levels in liver, gill and brain tissues of carps varied with concentration of TiO2-NPs suspensions and exposure time (up to 8 d). As a result, 100 and 200 mg/L TiO2-NPs caused statistically significant decrease in SOD, CAT and POD activities and significant increase in LPO levels in tissues (P < 0.05), suggesting that the fish exposed to these two concentrations of TiO2-NPs suffered from the oxidative stress. The extent of depletion of antioxidant enzymes activities and the elevation of LPO in the liver was the greatest, indicating that the liver might be the most susceptible organ to TiO2-NPs exposure. In addition, carps had gill pathologies including edema and thickening of gill lamellae as well as gill filaments, and liver pathologies including necrotic and apoptosis hepatocytes after exposed to 100 and 200 mg/L TiO2-NPs for 20 d. These results indicated a potential risk from TiO2-NPs released into the aqueous environment.

Human papillomavirus and cervical cancer behavioral surveillance in the US

In the US, federal and state behavioral surveillance systems routinely monitor self-reported sexual behavior and Papanicolaou (Pap) test use to identify high-risk populations, trends, and disparities and to guide and evaluate interventions for cervical cancer prevention and control. Clinical uptake of human papillomavirus (HPV) vaccination and testing necessitates the expansion of behavioral surveillance systems. Cervical disease is the main focus of HPV-related behavioral surveillance because of greater cancer incidence and mortality relative to other susceptible organs, and the availability of effective technologies for prevention and control. In the current study, a framework is presented for the types of behaviors to monitor, their conceptual and operational definitions, target populations, and evidence supporting the reliability and validity of self-report measures. An overview is also provided of 8 population-based and 2 provider-based data systems that are nationally representative and accessible for behavioral surveillance research. Ongoing surveillance at the national, state, and local level is critical for monitoring the dissemination of HPV technologies and their impact on reducing disparities in the detection of precursor lesions, incidence of invasive cancer, and mortality.

Protectant activity of reduced concentration copper sprays against Alternaria brown spot on ‘Fortune’ mandarin fruit in Spain

Alternaria brown spot (ABS) of mandarins is a serious disease of fruit and foliage of citrus, causing defoliation, fruit drop and rind blemishes on susceptible cultivars. In Spain, the disease causes severe losses on the late-maturing cultivars for export of ‘Fortune’ and ‘Nova’. Several fungicide sprays are needed to protect susceptible organs during the critical infection periods through the growing season. In Spain, copper compounds and mancozeb are the only fungicides registered for ABS control in conventional production, and copper is accepted for organic production as long as total dose does not exceed 6 kg ha −1 annually, but considerably higher amounts are currently applied for ABS control. Therefore, experiments were performed to evaluate the protective effect of reduced copper concentrations on fruits of the highly susceptible cultivar ‘Fortune’. All copper compounds evaluated effectively protected ‘Fortune’ fruit from infection for the 28-d period of study in two field trials, where a daily average of 9 h of leaf wetness was recorded. Reducing the concentration of copper in the spray tank from 1 to 0.5 g l −1 had no negative effect on persistence. Copper compounds applied at 0.5 g l −1 displayed excellent rain fastness in the simulated rainfall experiment, even with the highest precipitation of 90 mm. The use of reduced concentration copper sprays would diminish the economic and environmental costs of disease control and may assist growers moving towards organic production.

Oxidative stress and growth inhibition in the freshwater fish Carassius auratus induced by chronic exposure to sublethal fullerene aggregates

The rapid growth of nanotechnology is stimulating research concerning the potential environmental impacts of manufactured nanomaterials. The present study summarizes, to our knowledge, the first examination regarding the potential effects of chronic exposure (32 d) of aquatic organisms (juvenile carp [Carassius auratus]) to sublethal concentrations (0.04-1.0 mg/L) of fullerene aggregates (nC60/aq; i.e., C60 suspended in water after long-term stirring) with average diameters of approximately 349 and/or 1,394 nm. The results demonstrated that the antioxidant enzymes superoxide dismutase and catalase were induced significantly in the gills and liver of C. auratus exposed to nC60/aq for 32 d, whereas a nonenzymatic antioxidant, glutathione, decreased in all tested tissues. In addition, lipid peroxidation (LPO) levels decreased in most cases, especially in the gills and brain, but exposure to 1.0 mg/L of nC60/aq led to a significant (p < 0.01) increase in the LPO level in the liver. This increase in LPO level in combination with the observed oxidative stress suggested that the liver might be the target of or most susceptible organ to nC60/ aq exposure. Furthermore, the body weight and total length of juvenile carp exposed to 1.0 mg/L of nC60/aq for 32 d decreased significantly (p < 0.05), indicating that nC60/aq had an inhibitory effect on fish growth. The present findings imply that the oxidative stress induced by long-term exposure could be the main mechanism of the toxicity of nC60/aq to juvenile carp. This important work contributes to a better understanding of the potential health effects of exposure to manufactured nanomaterials on species in aquatic ecosystems.

Defect of the cerebellar vermis induced by prenatal gamma-ray irradiation in radiosensitive BALB/c mice.

The developing fetal brain is one of the most susceptible organs to irradiation insult. Prenatal irradiation-induced abnormalities in the cerebrum have been well examined in mouse fetuses. However, little information on abnormalities in the cerebellum caused by irradiation is available. Moreover, few reports have examined the chronological changes of the brain from the prenatal to the postnatal period. To analyze the chronological changes induced by irradiation, we exposed pregnant mice to gamma-ray irradiation on embryonic day 13.5 (E13.5) and investigated the histopathology of the cerebellum at several time points from E14.5 to postnatal day 28. BALB/cA mice were used, which is a radiosensitive strain, and C57BL/6J, which is a radioresistant strain. The irradiated BALB/c showed a remarkable vermis deficit after birth, and histological analysis demonstrated that there were severe losses of the external germinal layer (EGL) and Purkinke cell layer. TUNEL analysis shoed that apoptosis was strongly induce in the cerebellar anlage of the irradiated BALB/c compared to the C57BL/6J at E14.5. Immunohistochemical analysis revealed a significant decrease of phospho-histone H3 positive EGL cells in the irradiated BALB/c at E18.5 and E0, indicating that irradiation causes a decrease in the number of mitotic cells. The results suggest that the strong induction of apoptosis in radiosensitive BALB/c led to a decrease of proliferation activity in the cerebellar anlage during embryonic development, and consequently, severe cerebellar abnormality was evoked.

Analysis of Acute and Chronic Rejection in Multiple Organ Allografts From Retransplantation and Autopsy Cases of Multivisceral Transplantation

Small intestinal allografts in multivisceral transplantation are felt to be more susceptible to acute cellular rejection (ACR) and chronic rejection (CR) when compared with other allografts although there is little direct evidence for this impression. A total of 48 cases of multiple allograft specimens (37 autopsy and 11 explanted allograft cases) from 41 patients were evaluated in this study. Histopathologic assessments were performed with special concern to ACR and CR in allografts. The numbers of allografts available for evaluation were liver 37, small intestine 47, stomach 41, pancreas 45, and large intestine 25. Among 48 cases, 15 cases showed ACR (ACR case) and 12 showed CR (CR case) in at least one organ. In ACR cases, there was a statistically significant difference of organ-specific susceptibility to ACR among multivisceral allografts with the small intestinal allograft being the most susceptible (P<0.05). Severe ACR were observed only in small and large intestinal allografts. In CR cases, there was no statistically significant difference of organ-specific susceptibility to CR among multivisceral allografts with a tendency for the pancreas allograft to be the most susceptible (P=0.35). Our study clearly indicated variation in organ susceptibility to ACR and CR. Small intestinal allografts were the most susceptible organ to ACR in frequency and severity. Pancreatic allografts may be more susceptible to CR in comparison with ACR.

Infection control during GI endoscopy

This is one of a series of statements discussing the use of GI endoscopy in common clinical situations. The Standards of Practice Committee of the American Society for Gastrointestinal Endoscopy (ASGE) prepared this text. In preparing this guideline, a search of the medical literature was performed by using PubMed, supplemented by accessing the "related articles" feature of PubMed. Additional references were obtained from the bibliographies of the identified articles and from recommendations of expert consultants. When little or no data exist from well-designed prospective trials, emphasis is given to results from large series and reports from recognized experts. Guidelines for appropriate use of endoscopy are based on a critical review of the available data and expert consensus at the time the guidelines are drafted. Further controlled clinical studies may be needed to clarify aspects of this guideline. This guideline may be revised as necessary to account for changes in technology, new data, or other aspects of clinical practice. The recommendations were based on reviewed studies and were graded on the strength of the supporting evidence (Table 1). This guideline is intended to be an educational device to provide information that may assist endoscopists in providing care to patients. This guideline is not a rule and should not be construed as establishing a legal standard of care or as encouraging, advocating, requiring, or discouraging any particular treatment. Clinical decisions in any particular case involve a complex analysis of the patient's condition and available courses of action. Therefore, clinical considerations may lead an endoscopist to take a course of action that varies from these guidelines.

Transcriptional profile of red seabream iridovirus in a fish model as revealed by viral DNA microarrays

Red seabream iridovirus (RSIV) disease is a serious disease of many marine fish species in Japan and elsewhere. For a better understanding of the molecular pathogenic mechanism, we examined the transcriptional profile of RSIV in infected fish using a DNA microarray. Expression of RSIV open reading frames (ORFs) was first detected at about 5 days post-infection (d.p.i.), and accounted for about 45% of total ORFs. Almost all the ORFs (97-99%) were expressed at their maximum levels during 7-9 d.p.i. The expression levels and the number of expressed ORFs started to decrease at 10 d.p.i. These results suggest that pathogenesis of RSIV infection began at around day 5, and continued with high levels of viral multiplication until viral clearance by host antiviral defenses starting from around 10 d.p.i. A comparison of viral gene expressions in the spleen and kidney over the course of the infection suggests that RSIV preferentially targets the spleen. The spleen may thus be the most susceptible organ for diagnosis of iridoviral disease.

Exogenous heat shock protein 70 mediates sepsis manifestations and decreases the mortality rate in rats

Mammalian responses to bacterial lipopolysaccharide (LPS) from the outer membrane of Gram-negative bacteria can lead to an uncontrolled inflammatory reaction that can be deadly for the host. We checked whether heat shock protein 70 (Hsp70) protein is able to protect animals from the deleterious effects of bacterial LPS by monitoring the effect of exogenous Hsp70 injections before and after LPS administration. Our research with rats demonstrates for the first time that administration of exogeneous Hsp70 before and after LPS challenges can reduce mortality rates and modify several parameters of hemostasis and hemodynamics. Hsp70 isolated from bovine muscles showed significant protective effects against the impaired coagulation and fibrinolytic systems caused by LPS, and reduced the mortality caused by Escherichia coli and Salmonella typhimurium LPS injections significantly. Characteristically, Hsp70 preparations used in the experiments result in different effects when administered before and after an LPS challenge, and the effects of Hsp70 injections also differ significantly depending on the origin of the LPS (E coli vs S typhimurium). Based on our data, mammalian Hsp70 appears to be an attractive target in therapeutic strategies designed to stimulate endogenous protective mechanisms against many deleterious consequences of septic shock by accelerating the functional recovery of susceptible organs in humans.