Exposure to nicotine enhances acquisition of ethanol drinking by laboratory rats in a limited access paradigm

 Observations in humans suggest that the initial use of tobacco occurs in close temporal proximity to experimentation with alcohol. There have been relatively few research reports, however, examining possible interactions between these two agents. The present experiments examined the effect of nicotine exposure on the acquisition of ethanol drinking behavior in a limited access procedure. In experiment 1, rats were presented with 1-h access to ethanol solutions of increasing concentration for a period of 20 days. Subcutaneous injections of nicotine (0.6 or 1.2 mg/kg salt) or vehicle were administered 30 min prior to each ethanol presentation. Experiment 2 used a similar method, but rats were presented with water along with ethanol during the 1-h test session. Mecamylamine, a nicotinic receptor antagonist, was administered 30 min prior to the nicotine treatment. Nicotine was seen to produce a dose-dependent increase in ethanol drinking behavior which commenced at the 5% ethanol concentration and continued at 8% and again at 10%. In the second experiment, mecamylamine was observed to block completely the nicotine-induced increase in ethanol drinking behavior. The findings suggest that exposure to nicotine can facilitate the acquisition of ethanol drinking behavior in naive rats and that this effect is mediated by nicotine’s interaction at the nicotinic-cholinergic receptor. Received: 11 June 1998 / Final version: 1 October 1998     

Quantification of Mitral and Tricuspid Regurgitation Using Jet Centerline Velocities: An In Vitro Study of Jets in an Ambient Counterflow

A method for quantifying mitral and tricuspid regurgitant volume that utilizes a measure of jet orifice velocity U(0) - m/sec), a distal centerline velocity (U(m) - m/sec), and the intervening distance (X - cm) was recently developed; where jet flow rate (Q(cal) - L/min) is calculated as Q(cal) = (U(m)X)(2)/(26.46U(o)). This method, however, modeled the regurgitant jet as a free jet, whereas many atrial jets are counterflowing jets because of jet opposing intra-atrial flow fields (counterflows). This study concentrated on the feasibility of using the free jet quantification equation in the atrium where ambient flow fields may alter jet centerline velocities and reduce the accuracy of jet flow rate calculations. A 4-cm wide chamber was used to pump counterflows of 0, 4, and 22 cm/sec against jets of 2.3, 4.8, and 6.4 m/sec originating from a 2-mm diameter orifice. For each counterflow-jet combination, jet centerline velocities were measured using laser Doppler anemometry. For free jets (no counterflow), flow rate was calculated with 98% mean accuracy. For all jets in counterflow, the calculation was less accurate as: (i) the ratio of jet orifice velocity to counterflow velocity decreased (U(o)/U(c), where U(c) is counterflow velocity), i.e., the counterflow was relatively more intense, and (ii) centerline measurements were made further from the orifice. But although counterflow lowered jet centerline velocities beneath free jet values, it did so only significantly in the jet's distal portion (X/D > 16, i.e., >16 orifice diameters from the origin of the jet). Thus, the initial portion (X/D < 16) of a jet in counterflow behaved essentially as a free jet. As a result, even in significant counterflow, jet flow rate was calculated with >93% accuracy and >85% for jets typical of mitral and tricuspid regurgitation, respectively. Counterflow lowers jet centerline velocities beneath equivalent free jet values. This effect, however, is most significant in the distal portion of the jet. Therefore, regurgitant jets, although not classically free because of systolic atrial inflow or jet-induced intra-atrial swirling flows, will decay in their initial portions as free jets and thus are candidates for quantification with the centerline technique. (ECHOCARDIOGRAPHY, Volume 13, July 1996)     

The effects of cyclosporin A,tamoxifen, and medroxyprogesterone acetate on the enhancement of Adriamycin cytotoxicity in primary cultures of human breast epithelial cells

Summary Adriamycin (Adr), the single most active agent used in the treatment of breast cancer, may become ineffective as treatment progresses due to the development of multidrug resistant (MDR) tumors. A major mechanism associated with MDR is increased P-glycoprotein (Pgp) expression. This study examined the abilities of the anti-estrogen tamoxifen (TAM) and the progestin medroxyprogesterone acetate (MPA) as well as cyclosporin A (CsA), a known resistance modifier, to enhance the cytotoxic effects of Adr on human breast epithelial cells (HBEC) in primary culture. Pgp and estrogen receptor (ER) expression were determined in each of the cultures by immunocytochemical assays using the monoclonal antibodies C219 and H222 Sp, respectively. The Adr-sensitive, Pgp-, ER+ MCF-7 cell line and the Adr-resistant, Pgp+, ER-MCF7-AdrR cell line were used as controls. Primary cultures were categorized as HBEC from tissues with or without previous chemotherapy. Pgp was detected in 1 of the 15 cell cultures from tissues without previous chemotherapy and in 5 of the 6 cell cultures from tissues previously exposed to chemotherapy. Incubation with either CsA or MPA plus Adr enhanced Adr toxicity in Pgp+ but not Pgp- cell cultures, whereas TAM had no effect on the sensitivity of any of the cultures. Of the 21 primary cultures of HBEC, 3 were ER+. There was no correlation between the enhancement of Adr cytotoxicity and ER status. The data suggest that MPA as well as CsA may be useful as modifying agents in overcoming Pgp-associated multidrug resistance.     

Native Hawaiian Birth Weight and Infant Mortality: Is Birth in Hawai'i Protective?

PURPOSE OF THE PAPER: This study provides baseline information on the characteristics of Native Hawaiian mothers and the health status of their infants, comparing residents of Hawaii with those of the continental U.S. The impact of Hawaii residence on low birth weight and infant mortality among Native Hawaiians is assessed. SUMMARY OF METHODS UTILIZED: Data from the National Center for Health Statistics 1983­1987 Linked U.S. Live Birth and Infant Death file were used to examine parental characteristics, prenatal care use and infant outcomes using chi­square and logistic regression procedures. PRINCIPAL FINDINGS: Despite a higher sociodemographic risk profile among Hawaii resident mothers, preterm birth, low and very low birth weight percentages were similar. Continental infants had significantly highter percentages of very pre­term birth and macrosomia. Mortality rates in both the neonatal and post­neonatal periods, and for SIDS and perinatal causes were elevated among continental infants. Hawaii residence had a borderline protective effect on infant mortality, wehn sociodemographic and prenatal care differences were controlled. CONCLUSIONS: This study suggests a possibly protective effect of Hawaii residence on the health of Native Hawaiian infants during the period of following employer­mandated health insurance coverage but before the initiation of "gap­group" coverage and the Native Hawaiian Health Care Systems in Hawaii. RELEVANCE TO ASIAN PACIFIC ISLANDER AMERICAN POPULATIONS. This is the first report documenting the sociodemographic and health status of the growing number of Native Hawaiian mothers and their infants residing outside of Hawaii. Expanded health insurance coverage and culturally appropriate and accessible health care may contribute to improved infant health status in Hawaii. Their absence, along with possible barriers of sociocultural isolation, may account for the poorer than expected outcomes of continental infants and predict a widening gap between them and their counterparts in Hawaii. A follow­up study of the health status of Native Hawaiian mothers and infants, and their access to appropriate care in Hawaii and thei continental U.S. is recommended.     

Cell Type-specific Effects of the Neural Adhesion Molecules L1 and N-CAM on Diverse Second Messenger Systems

We have previously shown that the neural adhesion molecules L1 and N-CAM influence second messenger systems when triggered with specific antibodies at the surface of the phaeochromocytoma PC12 cell line (Schuch et al., Neuron, 3, 13 - 20, 1989). To determine whether the two molecules are linked to the same intracellular signalling cascades, independent of the cell type expressing them, or whether different neural cell types respond with different signal transduction mechanisms, we have investigated the effects of antibodies to L1 and N-CAM, and the isolated molecules themselves, on second messenger systems in different neural cell types. We have investigated cultures of cerebellar and dorsal root ganglion neurons and transformed Schwann cells and related these results to those obtained with the PC12 cell line. Here we show that addition of L1 and N-CAM antibodies and the isolated molecules themselves elicit cell type-specific responses that can be modulated by the substrate on which the cells are maintained. Depending on the cell type, cells respond to the triggering of L1 and N-CAM with antibodies, or addition of the purified molecules, by either up-regulation or down-regulation of inositol phosphate turnover, by a rise in intracellular Ca2+ levels dependent on or independent of the opening of voltage-gated Ca2+ channels, or by an increase or decrease in intracellular pH. Moreover, cerebellar neurons expressing N-CAM respond to addition N-CAM, but not to N-CAM antibodies, in contrast to the other neural cell types studied, which respond to both triggers. Furthermore, cerebellar neurons were the only cells to show a rise in cAMP levels in response to any of the ligands tested. This stimulation of cAMP production by L1 antibodies depended on the cross-linking of L1 molecules at the cell surface, whereas the other responses did not depend on clustering of L1. Simultaneous addition of L1 and N-CAM antibodies either elicited an additive or more than additive effect on the intracellular responses which, for cerebellar neurons, depends on the substrate on which the cells are maintained. These observations indicate that L1 and N-CAM or their antibodies activate cell type-specific intracellular signalling systems and that the two molecules can act interdependently or independently of each other.     

Residual curarization in the neonate after Caesarean section

The transplacental transfer and the neonatal effects of atracurium 0.3 mg.kg-1 (ED95) were compared with those of d-tubocurarine at the usual clinical dose of 0.3 mg.kg-1 (ED90) in 46 patients undergoing elective Caesarean section. The atracurium group (25 patients) was similar to the d-tubocurarine group (21 patients) as far as age, parity and time intervals between precurarization, induction, skin incision, muscle relaxant administration, hysterotomy and birth. The transplacental transfer of atracurium was lower than that of d-tubocurarine, with a feto-maternal ratio of 9 +/- 3% for atracurium and 12 +/- 5% for d-tubocurarine (P less than 0.05). The transplacental transfer of laudanosine was low at 14 +/- 5%, with blood levels of 0.101 +/- 0.032 microM.L-1 in the umbilical vein. Newborns in the two groups were comparable in terms of Apgar scores at one, five and ten minutes, as well as for NACS scores (neurological and adaptive capacity scoring test) at two and 24 hours after birth. However, at 15 min after birth, only 55% of newborns in whom the mothers received atracurium had a normal NACS score (greater than or equal to 35/40) compared with 83% of newborns in whom the mothers received d-tubocurarine (P less than 0.05). Further analysis of the five variables related to active muscle tone revealed that the modal score for active extension of the neck of newborns from the atracurium group was lower than for newborns from the d-tubocurarine group (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Pak-1 expression increases with progression of colorectal carcinomas to metastasis.

PURPOSE: The p21-activated kinase-1 (Pak-1) promotes cell motility and invasiveness. Pak-1 is activated by the Rac, Rho, and Cdc42 small GTPases in response to a variety of stimuli including ras and phosphatidylinositol 3'-kinase/AKT pathway activation. Because Pak-1 plays a central role in regulating cell motility and invasiveness, we sought to determine whether Pak-1 may be involved in the malignant progression of colorectal carcinoma. EXPERIMENTAL DESIGN: Pak-1 expression was examined by immunohistochemistry in archived tissues from normal human colons, tubular and tubulovillous adenomas, invasive adenocarcinomas (stages I-III/IV), and lymph node metastases (184 total specimens from 38 patients). Specific cytoplasmic immunostaining was evaluated for overall intensity and uniformity to derive a combined histoscore (stain intensity x percentage of epithelium stained). RESULTS: Pak-1 expression was increased significantly with colorectal cancer progression from normal tissue to lymph node metastases (P < 0.0001). Furthermore, Pak-1 expression was increased significantly in adenomas, invasive carcinomas, and lymph node metastases compared with normal colon (P < 0.0001). Strikingly, Pak-1 expression was significantly higher in lymph node metastases than in invasive cancers, adenomas, or normal colon (P < 0.0001). Moreover, in patients with multiple lesions representing different stages of disease, Pak-1 expression was increased specifically in the most advanced lesions. CONCLUSIONS: This study demonstrates that Pak-1 expression is increased significantly with malignant progression of human colorectal carcinoma. These data, along with numerous functional studies demonstrating a central role for Pak-1 activity in tumor invasiveness and motility, implicate Pak-1 as an exciting target for therapy of colorectal carcinoma.     

Developing a worker role: Stories of four people with mental illness

Background and Aims:  Work plays an important role in adults' well-being, irrespective of health status. Vocational rehabilitation can enable people with mental illness to return to open employment. A narrative approach was used to explore how individuals with a mental illness made sense of their work-related experiences.
Methods and Results:  Four Clubhouse members in open employment for at least 6 months completed in-depth, semistructured interviews, from which narratives were created to reveal events, significant persons and actions that assisted these individuals to resume work. Woven into the participants' stories were four 'impelling forces' contributing to a sense-of-self as a worker. These impelling forces were: support from significant others, the personal meaning of work, experiences within the Clubhouse programme, and the ongoing struggle with illness. Implications for occupational therapy practice are discussed.
Conclusion:  The findings of this study urge occupational therapists and others to provide opportunities to provide on-going support to people with a mental illness who seek paid employment.     

Maternal diet and infant leukemia: the DNA topoisomerase II inhibitor hypothesis: a report from the children's oncology group.

BACKGROUND: The MLL 11q23 translocation arises in utero and is present in 75% of infant leukemias. That MLL+ acute myeloid leukemia (AML) can arise following chemotherapy with DNA topoisomerase II (DNAt2) inhibitors suggests that these substances, which also occur naturally in foods, may contribute toward infant leukemia. We hypothesized that maternal consumption of dietary DNAt2 inhibitors during pregnancy would increase the risk of infant leukemia, particularly AML(MLL+). METHODS: This Children's Oncology Group case-control study consisted of 240 incident cases of infant acute leukemia [AML and acute lymphoblastic leukemia (ALL)] diagnosed during 1996 to 2002 and 255 random digit dialed controls. Maternal diet during pregnancy was determined through a food frequency questionnaire. An index of specific foods identified a priori to contain DNAt2 inhibitors as well as vegetables and fruits were created and analyzed using unconditional logistic regression. RESULTS: There was little evidence of an association between the specific DNAt2 index and leukemia overall and by subtype. An exception was AML(MLL+); odds ratios (95% confidence intervals) comparing the second to fourth quartiles to the first were 1.9 (0.5-7.0), 2.1 (0.6-7.7), and 3.2 (0.9-11.9), respectively (P for trend = 0.10). For the vegetable and fruit index, there were significant or near-significant inverse linear trends for all leukemias combined, ALL(MLL+), and AML(MLL-). CONCLUSION: Overall, maternal consumption of fresh vegetables and fruits during pregnancy was associated with a decreased risk of infant leukemia, particularly MLL+. However, for AML(MLL+) cases, maternal consumption of specific DNAt2 inhibitors seemed to increase risk. Although based on small numbers, these data provide some support for distinct etiologic pathways in infant leukemia.