Increased tumor establishment and growth after open vs laparoscopic bowel resection in mice

Background: Surgery can suppress immune function and facilitate tumor growth. Several studies have demonstrated better preservation of immune function following laparoscopic procedures. Our laboratory has also shown that tumors are more easily established and grow larger after sham laparotomy than after pneumoperitoneum in mice. The purpose of this study was to determine if the previously reported differences in tumor establishment and growth would persist in the setting of an intraabdominal manipulation. Methods: Syngeneic mice received intradermal injections of tumor cells and underwent either an open or laparoscopic cecal resection. In study 1, the incidence of tumor development was observed after a low dose inoculum; whereas in study 2, tumor mass was compared on postoperative day 12 after a high-dose inoculum. Results: In study 1, tumors were established in 5% of control mice, 30% of laparoscopy mice, and 83% of open surgery mice (p < 0.01 for all comparisons). In study 2, open surgery group tumors were 1.5 times as large as laparoscopy group tumors (p < 0.01), which were 1.5 times as large as control group tumors (p < 0.02). Conclusion: We conclude that tumors are more easily established and grow larger after open laparoscopic bowel resection in mice. Received: 27 October 1997/Accepted: 19 January 1998     

A novel bovine papillomavirus (BPV-6) causing true epithelial papillomas of the mammary gland skin: a member of a proposed new BPV subgroup

A papillomavirus has been isolated from frond epithelial papillomas of the bovine udder. It is clearly distinguishable from all other bovine papillomaviruses (BPVs) based on DNA sequence homology and antigenic properties and is thus characterised as a new entity, designated BPV-6. BPV-6 does not possess the interspecific papillomavirus antigen, its genomic DNA (7.2 kb) is smaller than, and does not show any sequence homology to BPV-1, BPV-2, or BPV-5, whereas it is approximately the same length as BPV-3 or BPV-4, with which it shares some sequence homology. The bovine papillomaviruses have been classified into two subgroups: subgroup A, composed of BPV-1, BPV-2, and BPV-5, all of which induce fibropapillomas, and subgroup B, composed of BPV-3, BPV-4, and BPV-6, all of which cause true epithelial papillomas.     

Longitudinal analysis of incomplete adolescent data.

An approach is illustrated for the analysis of longitudinal variables collected during adolescence. Since the method requires complete data, three techniques are compared for application when some individuals have missing values. These methods are implemented in a study of systolic blood pressures and dietary fat intakes collected longitudinally in adolescent girls. The value of adolescent systolic and fat variables in predicting systolic pressure in adult women is investigated.     

Detectability of fifteen aquatic micro/mesocosms

Zooplankton abundance and species richness in 15 untreated 12,000 L outdoor microcosms (n = 15) were monitored over the course of 1 year to document the inherent variability and statistical detectability between replicates. Statistical power analysis were applied to derive the statistically minimal detectable difference (MDD) between replicates with default values set at; α = 0.1 and β = 0.2. Copepod abundance and species richness generally demonstrated the best detectability at 0.31 and 0.16, respectively, (n = 15); 0.59 and 0.33 (n = 3). Total zooplankton abundance and species richness had the lowest detectabilities at 0.19 and 0.14, respectively, (n = 15); 0.35 and 0.3 (n = 3). Rotifers, due to their opportunistic and rapid life traits, had the lowest single-species abundance detectabilities at 0.54 (n = 15); 0.8 (n = 3), whereas macroinvertebrate species richness had the lowest detectability at 0.43 (n = 15); 0.7 (n = 3) over 1 year. We recommend a priori calibration of the study design relative to relevant MDDs. Moreover, it is suggested to consider alternatives to statistical null hypothesis testing.     

Association of a genetic marker at the corticotropin-releasing hormone locus with behavioral inhibition.

BACKGROUND: Behavioral inhibition to the unfamiliar (BI), a heritable temperamental profile involving an avoidant response to novel situations, may be an intermediate phenotype in the development of anxiety disorders. Corticotropin-releasing hormone (CRH) is a key mediator of the stress response through its effects on the hypothalamic-pituitary-adrenal axis and limbic brain systems. Transgenic mice overexpressing CRH exhibit BI-like behaviors, implicating this gene in the development of the phenotype. METHODS: We genotyped a marker tightly linked to the CRH locus in 85 families of children who underwent laboratory-based behavioral assessments of BI and performed family-based association analyses. RESULTS: We observed an association between an allele of the CRH-linked locus and BI (p =.015). Among offspring of parents with panic disorder, this association was particularly marked (p =.0009). We further demonstrate linkage disequilibrium between this marker and single nucleotide polymorphisms encompassing the CRH gene. CONCLUSIONS: These results are consistent with the possibility that variants in the CRH gene are associated with anxiety proneness.     

Improvement in sensitivity of allele-specific PCR facilitates reliable noninvasive prenatal detection of cystic fibrosis

BACKGROUND: Cell-free fetal DNA circulating in maternal blood has potential as a safer alternative to invasive methods of prenatal testing for paternally inherited genetic alterations, such as cystic fibrosis (CF) mutations. METHODS: We used allele-specific PCR to detect mutated CF D1152H DNA in the presence of an excess of the corresponding wild-type sequence. Pfx buffer (Invitrogen) containing replication accessory proteins and Taq polymerase with no proofreading activity was combined with TaqMaster PCR Enhancer (Eppendorf) to suppress nonspecific amplification of the wild-type allele. The procedure was tested on DNA isolated from plasma drawn from 11 pregnant women (gestational age, 11-19.2 weeks), with mutation confirmation by chorionic villus sampling. RESULTS: The method detected 5 copies of the CF D1152H mutant allele in the presence of up to approximately 100,000 copies of wild-type allele without interference from the wild-type sequence. The D1152H mutation was correctly identified in one positive sample; the only false-positive result was seen in a mishandled sample. CONCLUSIONS: This procedure allows for reliable detection of the paternally inherited D1152H mutation and has potential application for detection of other mutations, which may help reduce the need for invasive testing.     

Alteration of BACE1-dependent NRG1/ErbB4 signaling and schizophrenia-like phenotypes in BACE1-null mice

beta-Site APP-cleaving enzyme 1 (BACE1) is required for the penultimate cleavage of the amyloid-beta precursor protein (APP) leading to the generation of amyloid-beta peptides that is central to the pathogenesis of Alzheimer's disease. In addition to its role in endoproteolysis of APP, BACE1 participates in the proteolytic processing of neuregulin 1 (NRG1) and influences the myelination of central and peripheral axons. Although NRG1 has been genetically linked to schizophrenia and NRG1(+/-) mice exhibit a number of schizophrenia-like behavioral traits, it is not known whether altered BACE1-dependent NRG1 signaling can cause similar behavioral abnormalities. To test this hypothesis, we analyze the behaviors considered to be rodent analogs of clinical features of schizophrenia in BACE1(-/-) mice with impaired processing of NRG1. We demonstrate that BACE1(-/-) mice exhibit deficits in prepulse inhibition, novelty-induced hyperactivity, hypersensitivity to a glutamatergic psychostimulant (MK-801), cognitive impairments, and deficits in social recognition. Importantly, some of these manifestations were responsive to treatment with clozapine, an atypical antipsychotic drug. Moreover, although the total amount of ErbB4, a receptor for NRG1 was not changed, binding of ErbB4 with postsynaptic density protein 95 (PSD95) was significantly reduced in the brains of BACE1(-/-) mice. Consistent with the role of ErbB4 in spine morphology and synaptic function, BACE1(-/-) mice displayed reduced spine density in hippocampal pyramidal neurons. Collectively, our findings suggest that alterations in BACE1-dependent NRG1/ErbB4 signaling may participate in the pathogenesis of schizophrenia and related psychiatric disorders.