Immune-compromised state in the rat pancreas after chronic alcohol exposure: the role of peroxisome proliferator-activated receptor gamma.

Alcohol exposure is known to sensitize acinar cells to various insults but the pathophysiological mechanisms of alcoholic pancreatitis remain unknown. Alcohol abuse has been shown to mediate an anti-inflammatory response and periods of immune suppression seem to be associated with organ injury and mortality. The purpose of this study was to determine the mechanisms by which alcohol exerts transcriptional activities in the rat pancreas and how alcohol alters the inflammatory response. Using the Lieber-DeCarli alcohol/control diet, rats that were fed with alcohol over 14 weeks demonstrated a decrease of inflammatory cells in pancreatic tissue compared to controls. The anti-inflammatory effects of alcohol were confirmed by decreased expression of pro-inflammatory cytokines including TNFalpha, IL-1beta, IL-18, TGFbeta, and MCP-1. In addition, alcohol significantly increased the activity of PPARgamma, which is a known anti-inflammatory transcription factor, while pro-inflammatory factors including AP-2 and EGR-1 were significantly suppressed. NFkappaB binding showed a tendency towards a reduction. Electron microscopy studies revealed enlarged and injured mitochondria and lysosomes, accompanied by peri-cellular fibrosis. Furthermore, alcohol exposure increased the activities of trypsin and cathepsin B, both known to be critical in initiating acinar cell injury and pancreatitis. Despite the known alcohol-mediated acinar cell and mitochondrial injury, the mitochondrial-mediated apoptotic pathway was attenuated. These data demonstrate that the pancreas exposed to alcohol maintains an anti-inflammatory state by activating PPARgamma. Intracellular mitochondrial and lysosomal damage after chronic alcohol exposure induces premature activation of digestive enzymes and establishment of peri-cellular fibrosis in the absence of inflammation.

Changes in myocardial blood supply during experimental hypertension treated with verapamil in rabbits.

Rabbit hearts were studied at different periods of experimental arterial hypertension and its treatment with verapamil. Morphological study revealed a progressive decrease in the number of capillaries per unit mass during the development of myocardial hypertrophy in hypertensive hearts. In hypertensive animals treated with verapamil the density of capillaries in both ventricles did not decrease, but verapamil injected to intact animals sharply decreased this parameter.

Initial mechanisms of the development of hypertonic heart.

In rabbits, arterial hypertension was simulated according to Goldblatt. One, 2, 4, and 6 weeks after surgery, the hearts of control and experimental animals were extirpated for morphological examination. In semithin sections of the left and right ventricles, morphometry was performed using an Avtandilov grid. Ultrathin sections of these organs were examined under an electron microscope. It was found that the initial signs of myocardial hypertrophy appeared soon after hypertension modeling, and more early in the right ventricle. Activation of apoptosis was noted in cardiomyocytes of both ventricles, and its intensity correlated with the degree of myocardial hypertrophy. It is hypothesized that apoptosis limits the development of hypertrophy in the myocardium.

Prenatal diagnosis and fetal pathology in a Turkish family harboring a novel nonsense mutation in the lysosomal alpha-N-acetyl-neuraminidase (sialidase) gene.

We report a Turkish family with parental consanguinity and at risk for sialidosis type II, an inherited autosomal recessive disorder caused by lysosomal alpha-N-acetyl-neuraminidase (sialidase, NEU1) deficiency. The proband was a premature male infant that presented with hydrops, hepatomegaly, respiratory distress syndrome, and anemia and that died of respiratory insufficiency 2 months after birth despite intensive care. An abnormally increased [14C]methylamine incorporation and an isolated deficiency of lysosomal alpha-N-acetyl-neuraminidase were found in cultured skin fibroblasts. A previous pregnancy of the mother terminated in a spontaneous abortion in the 13th week of gestation. A successive pregnancy showed hydrops fetalis, and an enzymatic assay of cultured amniotic fluid cells indicated a deficiency of alpha-N-acetyl-neuraminidase. Following pregnancy termination at 20 weeks gestation, light microscopy of fetal tissues revealed classic vacuolation not only in liver, bone marrow, brain, and kidney, but also in endocrine organs such as the thyroid gland, adrenal gland, hypophysis, and testes, and in the thymus. DNA analysis of the family showed that both the proband and the third sibling had a novel homozygous nonsense point mutation at nucleotide 87 in exon 1 of the alpha-N-acetyl-neuraminidase (neu1) gene causing a substitution of tryptophan at codon 29 by a termination codon (W29X). DNA sequencing of polymerase chain reaction products identified the parents as heterozygous carriers. To detect neu1 mRNA expression, a real-time reverse transcription/polymerase chain reaction was performed, and similar rates of neu1 mRNA expression were found in the fibroblasts of the fetus, the 2nd sibling, and in controls. The very early termination codon with complete loss of neuraminidase activity is probably the molecular basis of the unusually severe vacuolation pattern in this form of congenital sialidosis.

Possible mechanism of regression of myocardial hypertrophy.

Structure of the myocardium was studied in rabbits with renovascular hypertension during the development of myocardial hypertrophy and its regression under the effect of beta-adrenoceptor antagonist lopressor. Myocardial hypertrophy was associated with ultrastructural changes in cardiomyocytes, while lopressor therapy led to their regression and normalization of cardiomyocyte ultrastructure. Regression of hypertrophic changes was accompanied by a marked increase in the number of extracellular nuclei, which indicated enhanced apoptosis of cardiomyocytes.

Assessment and epidemiologic issues related to fatigue.

At The University of Texas M. D. Anderson Cancer Center, a multidisciplinary workgroup was assembled to review issues, current research, and areas of future research related to the assessment and epidemiology of cancer-related fatigue. Interactive discussion facilitated by a moderator determined the major areas of focus for future research in this arena. The group's ideas were presented to the entire conference following the session. Several gaps in current research related to the assessment and epidemiology of cancer-related fatigue were identified.

Oncology nurses' knowledge, practice, and educational needs regarding cancer genetics.

This study evaluated oncology nurses' knowledge of cancer genetics and related topics, and identified current practice patterns and perceived educational needs in this area. A 54-item study questionnaire was mailed to a random sample of 1,200 Oncology Nursing Society (ONS) members and 75 members of the ONS-Cancer Genetics Special Interest Group; 656 (51%) of those eligible responded. After exclusions, we analyzed 573 responses. Most respondents were Caucasian, female, and worked in hospital or outpatient settings. Half were staff nurses and 8% specialized in cancer genetics. Respondents with higher levels of nursing education or with continuing education in cancer genetics, who worked in positions other than staff nurses, and whose primary practice area was cancer genetics had significantly higher mean scores overall on questions measuring knowledge of cancer genetics and related areas. Higher perceived educational needs to improve knowledge or practice related to cancer genetics at basic, intermediate or advanced levels were associated with all or some of the following variables: lower education; hospital/ outpatient or managed care/private practice settings; lack of continuing education in cancer genetics, and positions other than advanced practice nurses. Although nearly half of the respondents had received patient inquiries regarding cancer genetics, only 35% were aware of referral resources and 26% had made such referrals. These findings may be used to develop targeted educational approaches that prepare oncology nurses to incorporate cancer genetics into any level of practice.

The role of oncology nurses in gene therapy.

In February 2001, the Human Genome Project international consortium announced the publication of a draft sequence and initial analysis of the human genome. Although a definitive count of human genes must await further experimental and computational analysis, scientists now estimate that the human genome contains 30000-35000 genes--a much smaller number than initially estimated. The advances in treatment which will result from this research and our improved understanding of cancer at a molecular level will rapidly change the management of cancer. Gene therapy represents one new approach to treatment, but is currently still experimental. This article reviews the important role of the oncology nurse as a member of the multidisciplinary team caring for patients who receive gene therapy as part of a clinical trial.

EPR and NMR spectroscopic studies of [MoL2(MeC identical to CMe)Cp]z (L = P-donor ligand, z = 0 and 1): fluxionality in a metal-alkyne redox pair.

Variable temperature NMR and EPR spectroscopic studies provide rates and activation parameters for alkyne rotation and oscillation, respectively, in the fluxional redox pair [Mo(P(OMe)3)2(MeC identical to CMe)Cp][BF4] (diamagnetic) and [Mo(P(OMe)3)2(MeC identical to CMe)Cp] (paramagnetic).

Regulation of type 1 pili expression as exemplified by Escherichia coli strain m17.

Studies of E. coli strain M17 colibacterin and its derivatives showed that fimH gene regulates morphological characteristics of type 1 fimbria and cell piliation on the whole. Gene fimH has a negative effect and decreased the percentage of piliated cells in the population and piliation of individual cells, which does not agree with its role of a positive regulator.

Cancer genetics and nursing practice: what every gastroenterology nurse needs to know.

Most nurses will care for and provide health information about cancer to a patient at some point in their careers. Cancer care will change dramatically in the coming years as a result of the translation of information gained from the Human Genome Project into clinical practice and the enhanced understanding of cancer at a molecular level. A select group of cancers, known as hereditary cancers, result from mutations in the germline that confer a greatly increased lifetime risk of developing cancer. Advances in technology and discoveries stemming from the Human Genome Project now provide the means to test individuals for the presence of mutations associated with some known hereditary cancer syndromes. Of particular importance to gastroenterology nurses are hereditary colorectal cancer syndromes. Although many ethical, legal, and psychosocial issues associated with testing remain unresolved, predisposition genetic testing is having a significant impact on health care. Nurses will have vital roles in the future assessing patients and their family members for increased cancer risk, educating them about the availability of testing, making referrals for cancer genetic counseling and risk assessment, and providing follow-up care in the community for patients found to be at increased risk.

Tropism of human cytomegalovirus for endothelial cells is determined by a post-entry step dependent on efficient translocation to the nucleus.

Marked interstrain differences in the endothelial cell (EC) tropism of human cytomegalovirus (HCMV) isolates have been described. This study aimed to define the step during the replicative cycle of HCMV that determines this phenotype. The infection efficiency of various HCMV strains in EC versus fibroblasts was quantified by immunodetection of immediate early (IE), early and late viral antigens. Adsorption and penetration were analysed by radiolabelled virus binding assays and competitive HCMV-DNA-PCR. The translocation of penetrated viral DNA to the nucleus of infected cells was quantified by competitive HCMV-DNA-PCR in pure nuclear fractions. The intracytoplasmic translocation of capsids that had penetrated was followed by immunostaining of virus particles on a single particle level; this was correlated with the initiation of viral gene expression by simultaneous immunostaining of viral IE antigens. The infectivity of nonendotheliotropic HCMV strains in EC was found to be 100-1000-fold lower when compared to endotheliotropic strains. The manifestation of this phenotype at the level of IE gene expression indicated the importance of initial replication events. Surprisingly, no interstrain differences were detected during virus entry. However, dramatic interstrain differences were found regarding the nuclear translocation of penetrated viral DNA. With nonendotheliotropic strains, the content of viral DNA in the cell nucleus was 100-1000-fold lower in EC when compared to endotheliotropic strains, thereby reflecting the strain differences in IE gene expression. Simultaneous staining of viral particles and viral IE antigen revealed that interstrain differences in the transport of penetrated capsids towards the nucleus of endothelial cells determine the EC tropism of HCMV.

Recent advances in immunotherapy and monoclonal antibody treatment of cancer.

OBJECTIVES: To review the immune response and tumor immunology, and to provide an update on the success and obstacles to targeted therapy using monoclonal antibodies and antibody conjugates. DATA SOURCES: Research articles and textbooks. CONCLUSIONS: Ongoing studies are exploiting the targeting properties of the immune system to improve anticancer therapy. Both monoclonal antibodies and immunoconjugates have shown promise in treatment of specific diseases. IMPLICATIONS FOR NURSING PRACTICE: The rapid growth of molecular techniques has allowed for the development of new anticancer therapies. Since nurses are intimately involved in the delivery of such therapy as well as in educating patients regarding risks and benefits, they must be knowledgeable.