CD97, but not its closely related EGF-TM7 family member EMR2, is expressed on gastric,pancreatic, and esophageal carcinomas

CD97 expression is related closely to the dedifferentiation and tumor stage in thyroid carcinomas. We systematically examined the role of CD97 and its closest relative, EMR2, in normal and malignant gastric, esophageal, and pancreatic tissue. The normal tissues were EMR2-, whereas CD97 was expressed slightly in the parietal cells of gastric mucosa and in exocrine pancreatic cells. Interestingly, intralobular and interlobular pancreatic ducts were CD97+. All tumors were EMR2-. CD97 was expressed by 44 of 50 gastric, 14 of 18 pancreatic, and 10 of 13 esophageal carcinomas. Of the 44 gastric cancers, 27 showed disseminated or scattered tumor cells at the invasion front with stronger CD97 expression than tumor cells located in solid tumor formations. There was no correlation between CD97 levels in the tumors or soluble CD97 in the serum samples and the clinicopathologic features of the patients. Taken together, significant numbers of gastric, esophageal, and pancreatic carcinomas are CD97+, whereas its homolog, EMR2, does not have any role in such tumors.     

Up-Regulation of TH2 feto-placental levels could be involved in the protective effect of low-molecular-weight heparin treatment on spontaneous abortion in mice

The cytokines that predominate at the healthy maternal fetal interface are compatible with those produced by Th2/3 cells. Th1 and Th2 type immunity are mutually inhibitory and cytokine profiles are regulated in part by maternal sex steroids. The immune and endocrine equilibrium required for pregnancy success may be modified by external factors including stress, infection and altered maternal nutrition. The latter has received surprisingly little attention particularly as the effects of nutrition on immunity per se are widely documented. We have used animal models to investigate the effects of altered maternal diet on both immune and endocrine mechanisms important for pregnancy success. In rodents, maternal deficiencies in iron and vitamin A have been shown to negatively alter the expression of placental cytokines and in the case of vitamin A, increase placental apoptosis. In a highly controlled sheep model, overfeeding young growing females carrying singleton pregnancies restricts placental growth resulting in the premature delivery of low birth weight lambs. This is associated with reduced maternal concentrations of progesterone, placental lactogen, PSPB, GH and increased insulin, IGF-1, leptin and thyroid hormones (Wallace et al. Reprod 2001; 122:347–357). At day 80 of gestation (term=145) the placentae of overfed dams exhibit reduced expression of proliferation markers, predominantly in the fetal trophectoderm, and increased expression of the pro-apoptotic protein bax. These data indicate an altered balance between placental proliferation and apoptosis, possibly linked to maternal endocrine status. We conclude that maternal diet has considerable impact on immuno-endocrine mechanisms critical for pregnancy success.     

Rapid leukocyte integrin activation by chemokines

Summary: Chemokines control selective targeting of circulating leukocytes to the microvasculature by triggering inside-out signal transduction pathways leading to integrin-dependent adhesion. Integrin activation by chemokines is very rapid, is downmodulated within minutes and appears to involve both enhanced heterodimer lateral mobility on the plasma membrane, facilitating encounters with dispersed ligand, as well as induction of a high-affinity state. These two modalities of integrin activation by chemokines involve distinct signaling pathways in the cell, yet complement each other functionally, allowing binding of rolling cells under conditions of low as well as high ligand density. Recent data show that chemokines generate both pro- and anti-adhesive intracellular signaling events, whose equilibrium is likely to be relevant to the kinetics of adhesion and de-adhesion, and to cell movement during diapedesis and chemotaxis. Importantly, chemokines utilize different signaling mechanisms to modulate the activity of distinct integrin subtypes. These recent advances suggest that chemokines may regulate adhesive responses of immune cells based not only on patterns of chemokine receptor expression, but also on variable signaling pathways that can modulate the pro-adhesive responses of leukocytes as a function of their differentiated state, and of the local microenvironment.     

Parenting stress and parental bonding

Attachment experiences are thought to be important because of their implications for later development. The authors' aim with the questionnaire-based study was to investigate the differences between recalled parental bonding regarding 4 types of maternal and paternal bonding with respect to experienced parenting stress caused by child characteristics, parent attributes, and life events under the consideration of the child's gender and age. The authors gathered parental bonding behavior data with the German version of the Parental Bonding Instrument (PBI). The authors assessed parenting stress with their German version of the "Parenting Stress Index (PSI)." They found significant differences among 120 mothers grouped in the 4 maternal and the 4 paternal bonding types regarding parenting stress caused by child, maternal bonding: F(5, 113) = 4.13, p = .002, paternal bonding: F(5, 111) = 8.50, p < or = .0001, and parent characteristics, maternal bonding: F(5, 113) = 3.33, p = .008, paternal bonding: F(5, 111) = 7.80, p < or = .0001. The lowest level of parenting stress was experienced by mothers who themselves recalled the "optimal parental bonding type" with respect to the child and parental domain. The authors did not find any significant differences between the 4 maternal, F(5, 113) = 1.25, p = .29, and the 4 paternal, F(5, 111) = 1.87, p = .106, bonding types with respect to the life stress. According to the authors' findings, the representation of attachment relationships seems to have a special impact on the adult's capacity to cope with challenges and stress, either directly or indirectly as an internal working model of attachment. For the clinical practice, these findings seem to recommend the combination of both the PSI and PBI regarding the diagnostic of stressful mother-child system to plan an optimal intervention program.     

Molecular genetic methods in the diagnosis of hematologic neoplasms

Leukemias and lymphomas are monoclonal neoplasms that arise as a result of molecular abnormalities. These abnormalites are diverse but can be grouped into two general categories, chromosomal translocations that usually result in oncogene activation and inactivation of tumor suppressor genes. Recent advances in our understanding of chromosomal translocations have led to improved classification of leukemias and lymphomas. For example, the t(9;22)(q34;q11) is now considered a defining feature of chronic myeloid leukemia, and the t(2;5)(p23;q35) defines a clinically and biologically unique subset of anaplastic large cell lymphomas. In this review, we focus on chromosomal translocations in hematologic neoplasms and the techniques used for their detection. We also briefly discuss tumor suppressor genes and assessment of clonality in lymphoid neoplasms.     

Gene therapy for pituitary tumors

Pituitary tumors are the most common primary intracranial neoplasms. Although most pituitary tumors are considered typically benign, others can cause severe and progressive disease. The principal aims of pituitary tumor treatment are the elimination or reduction of the tumor mass, normalization of hormone secretion and preservation of remaining pituitary function. In spite of major advances in the therapy of pituitary tumors, for some of the most difficult tumors, current therapies that include medical, surgical and radiotherapeutic methods are often unsatisfactory and there is a need to develop new treatment strategies. Gene therapy, which uses nucleic acids as drugs, has emerged as an attractive therapeutic option for the treatment of pituitary tumors that do not respond to classical treatment strategies if the patients become intolerant to the therapy. The development of animal models for pituitary tumors and hormone hypersecretion has proven to be critical for the implementation of novel treatment strategies and gene therapy approaches. Preclinical trials using several gene therapy approaches for the treatment of anterior pituitary diseases have been successfully implemented. Several issues need to be addressed before clinical implementation becomes a reality, including the development of more effective and safer viral vectors, uncovering novel therapeutic targets and development of targeted expression of therapeutic transgenes. With the development of efficient gene delivery vectors allowing long-term transgene expression with minimal toxicity, gene therapy will become one of the most promising approaches for treating pituitary adenomas.     

Localization of 5-hydroxytryptamine-like immunoreactive cells and nerve fibers in the rat female reproductive system.

The presence of 5-hydroxytryptamine (5-HT)-like immunoreactivity (IR) was studied in the rat female reproductive system using polyclonal antibodies directed against 5-HT. Moreover, 5-HT levels in the ovary, oviduct, uterus, and cervix were measured by high-pressure liquid chromatography with electrochemical detection. The highest 5-HT concentrations were found in the oviduct, followed in descending order by the cervix, the ovary, and the uterus. Most 5-HT-like IR was observed in the cytoplasm of mast cells. These cells were found in the connective tissue around the fimbria, in the oviduct, in the uterus, and in the ovary. Mast cells are clustered in the proximity of the parenchymal blood vessels. Moreover, a few 5-HT-like nerve fibers were found distributed mainly perivascularily in the uterine cervix and in the uterine horns as well as in the oviduct. IR nerve fibers were rarely seen within the ovary. The present data provide direct evidence that 5-HT in the female reproductive system not only is associated with mast cells but is located in nerve fibre-like structures as well. The functional significance of this probable 5-HT-ergic innervation of the female reproductive tract discovered in the present study should be clarified in future investigations.     

Casein is an essential cofactor in autoantibody reactivity directed against the C-terminal SmD1 peptide AA 83-119 in systemic lupus erythematosus

The C-terminal peptide SmD1(83-119) has been identified as an important autoantigen in systemic lupus erythematosus (SLE). ELISA studies have shown that roughly 70% of all sera from patients with SLE react with this peptide. Previous findings revealed that the addition of blocking agents and sample dilution buffers influences the discrimination between positive and negative anti-SmD1(83-119) sera in SLE. The aim of the present study was to identify possible cofactors in the anti-SmD1(83-119) reactivity. We therefore tested SLE sera (n=6) for anti-SmD1(83-119) reactivity by ELISA and analysed the effects of different blocking agents (1% skim milk, 1% gelatin, and 1% BSA). In our investigation, lipids were extracted from skim milk using dichlomethane, and the putative fraction was tested to assess the assay's ability to discriminate between positive and negative sera. The effects of enzymatic digestion by casein were analyzed, and different concentrations of casein were used to determine the role of this protein in the detection of anti-SmD1(83-119) antibodies by ELISA. Furthermore, rabbits were immunized with SmD1(83-119) adsorbed to casein and control proteins. One percent skim milk was the most effective blocking agent and sample dilution buffer for the discrimination between positive and negative sera. As demonstrated by SDS electrophoresis, the discriminative capacity was influenced by enzymatic digestion of skim milk proteins, but not by lipid extraction. Differences in anti-SmD1(83-119) reactivity upon variation of the casein concentration suggest that the protein plays a significant role in the detection of anti-SmD1(83-119) antibodies. However, our immunisation studies did not show any effect of casein on anti-SmD1(83-119) reactivity, suggesting that it has no immunogenic effect on the anti-SmD1(83-119) response. In conclusion, casein seems to be an important cofactor in autoantibody reactivity directed against the C-terminal SmD1(83-119) peptide and probably functions by changing the conformation of the peptide's critical epitope.