Obesity and GERD impair esophageal epithelial permeability through 2 distinct mechanisms.

BACKGROUND: The mechanism by which obesity leads to damage independent of reflux is unclear. We aimed to determine the influence of obesity on mean nocturnal baseline impedance (MNBI), a functional measure of the epithelial barrier, in the presence and absence of acid reflux, using ambulatory pH impedance measurements. METHODS: Twenty-four-hour pH impedance studies performed off medications in Caucasian men with a normal endoscopic examination were assessed for level of acid exposure and MNBI. Four patient groups were studied: Group 1, Not obese and normal acid exposure; Group 2, Obese and normal acid exposure; Group 3, Not obese and increased acid exposure; and Group 4, Obese with increased acid exposure. RESULTS: One hundred patients were studied (25 in each group). Mean esophageal mucosal impedance (MI) was substantially lower in obese patients without reflux (Group 2) and non-obese patients with reflux (Group 3) compared to normal controls (non-obese, no reflux, Group 1). MI was progressively lower in the distal (vs the proximal) esophagus in GER patients, compared to those without GER. This difference persisted in the presence or absence of obesity. In contrast, in obese patients, the mean MI was significantly lower throughout the esophagus when compared to the non-obese patients and also persisted in the presence and absence of accompanying reflux. Obesity and reflux were both independently negatively correlated with MI. CONCLUSION: Obesity is associated with abnormal esophageal MNBI. In contrast to gastro-esophageal reflux, this decrease is pan-esophageal. These data may support a systemic mechanism by which obesity alters the esophageal barrier function.

Differential expression, alternative splicing, and adhesive properties of the zebrafish δ1-protocadherins.

Protocadherins comprise the largest family within the cadherin superfamily of cell surface receptors. Here, we characterize the δ1-protocadherin subfamily during the development of the zebrafish nervous system. In zebrafish, there are five δ1-protocadherins: pcdh1a, pcdh1b, pcdh7a, pcdh7b, andpcdh9. Each protocadherin gene is highly homologous to its human ortholog. While the expression pattern in the developing CNS is similar for each δ1-protocadherin, with labeling observed in all major subdivisions, the detailed patterns are distinct. In addition, we provide evidence for alternative splicing of the pcdh7b and pcdh9 genes, resulting in variation in their respective cytoplasmic domains. As protocadherins are widely regarded to act as cell adhesion molecules, we used in vitro assays of δ1-pcdh ectodomains to directly test their adhesive properties. We found no evidence for calcium-dependent, homophilic adhesion, contrasting sharply with the behavior of classical cadherins.

Milking frequency, estradiol cypionate, and somatotropin influence lactation and reproduction in dairy cows.

Our objectives were to determine lactational and reproductive outcomes in response to increased milking frequency (MF), injection of estradiol cypionate (ECP), and treatment with bovine somatotropin (bST). Lactating dairy cows (n = 144) were blocked by lactation number (1 vs. 2+) and assigned randomly to a 2 x 2 x 2 factorial experiment consisting of 8 treatment combinations: 1) MF consisting of 4x daily milking (4x) for the first 30 d in milk (DIM) vs. 2x daily milking (2x), with all cows milked 2x after 30 DIM; 2) 10 mg of ECP given postpartum at 8 +/- 3 DIM versus controls that received ECP diluent (oil); and 3) biweekly bovine somatotropin (bST), starting sometime after 60 DIM, versus no bST. Ovulation before the first artificial insemination was synchronized by using Heatsynch (GnRH injection 7 d before PGF2alpha followed in 24 h by ECP), and cows were artificially inseminated after detected estrus or at 48 h after ECP, whichever came first. Pregnancy was assessed by transrectal ultrasonography 28 to 30 d after artificial insemination. Daily yield and weekly components of milk were measured during the first 90 DIM. Intervals to first and second postpartum ovulation were unaffected by treatment, but cows were in estrus earlier after 2x (24 +/- 4 d) than 4x (41 +/- 4 d) daily MF, and sooner after ECP (25 +/- 3 d) than after oil (39 +/- 4 d) treatment. Pregnancy rates among 4x cows increased for ECP versus oil (52.8 vs. 27.8%) more than for cows with 2x MF treated with ECP versus oil (50.0 vs. 39.4%). Increased MF increased daily milk yields and energy-corrected milk yields during the first 30 DIM. Although milk yields were increased acutely by ECP during the 10 d after its injection, subsequent milk yields were decreased for ECP-treated cows previously milked 4x daily. Treatment with bST increased overall daily milk yields most in cows previously milked 2x daily and treated with oil and those milked 4x daily and treated with ECP. We concluded that early postpartum ECP injection increased pregnancy rates, but generally had detrimental effects on milk yields after 30 DIM for ECP-treated cows previously milked 4x daily, unless those cows also were treated with bST.

There really is a difference: home care competencies.

BACKGROUND: More nurses are turning to home care agencies as sources of employment because of mergers, alliances, and increased emphasis on outpatient services. The unique differences in the home care nursing role necessitate adequate orientation and ongoing competency validation. METHOD: A review of relevant nursing literature was conducted. The author also relied on her experiences as a home care educator. RESULTS: Nurses who enter the specialty of home care nursing can expect to learn specific competencies that are unique to home care. CONCLUSION: Specific competencies unique to home care are proposed. There is scant published research regarding home care competencies to date.

Wholism for aging families: meeting needs of caregivers.

Family caregiving of a frail older person is an increasingly common phenomenon. Caregivers are confronted with new roles and responsibilities that provide both challenges and opportunities. Family issues that require expert nursing attention include role reversal, unresolved conflicts, caregiver immersion, elder mistreatment, and caregiving from a distance. Comprehensive geriatric assessment provides a foundation for intervening with families. Nurses are instrumental in providing a family perspective that meets the needs of frail older persons and their caregivers thus providing wholistic care.

Effective initial therapy of advanced breast cancer with fluorouracil and high-dose, continuous infusion calcium leucovorin.

PURPOSE: The use of leucovorin (LV) to modulate fluorouracil (FU)-mediated inhibition of thymidylate synthase has been shown both in vitro and in vivo to improve the antitumor activity of this drug. Based on our previous demonstration that this combination was active in heavily pretreated patients with prior FU exposure, we performed a phase II study of FU and high-dose intravenous calcium LV in patients with advanced breast cancer who had been exposed to no more than one prior chemotherapy regimen. PATIENTS AND METHODS: Fifty-one female patients with metastatic breast cancer were entered onto this trial. Patients with metastatic disease limited to soft tissue, lymph nodes, skin, and pulmonary nodules were allowed no prior chemotherapy for advanced disease. Those with metastases in the liver or a lymphangitic pattern on chest x-ray were allowed either a single prior regimen for advanced disease or no therapy for metastatic disease if less than 1 year had elapsed since the completion of adjuvant chemotherapy. FU was given daily for 5 days at 400 mg/m2/d with calcium LV, 500 mg/m2/d, beginning 24 hours before and continuing 12 hours after the first and last FU doses, respectively. RESULTS: The overall objective response rate among 45 eligible patients was 36% (95% confidence interval, 22% to 51%). Fourteen of 31 patients in the soft tissue category responded (45%), and two of 14 in the visceral category experienced an objective response (14%). The median response duration was 5 months. Toxicities were moderate leukopenia and mucositis. CONCLUSIONS: FU plus LV is an active first-line regimen with antitumor efficacy comparable to that of the anthracyclines, which warrants further exploration in combination with other agents active in advanced breast cancer. FU plus LV in this schedule is also an excellent alternative for patients with medical contraindications to more intensive combination chemotherapy regimens.

Persistence of one species of oncovirus in mixed infection after antiserum treatment or transspecies rescue.

Attempts were made to change the envelope of murine sarcoma virus (MSV) from B-MuX (a xenotropic murine leukaemia virus isolate) to feline leukaemia virus (FeLV) by infecting cat cells with MSV(B-MuX), adding excess FeLV as helper and using mouse serum oncovirus-inactivating factor or anti-B-MuX serum. In several attempts, virus from single foci of MSV initially contained only MSV(FeLV) but on passage each showed a minimal persistence of B-MuX. To eliminate the B-MuX component, MSV(B-MuX) was subjected to two consecutive transspecies rescues. The first was performed by co-cultivation of MSV(B-MuX)-producing quail cells with mouse 3T3FL cells, which are completely non-permissive for B-MuX, and pure ecotropic Friend Eveline strain of murine leukaemia virus (F-MuLV); this resulted in apparently pure MSV(F-MuLV). Second, these MSV(F-MuLV)-infected 3T3FL cells were co-cultivated with FeLV and cat cells, which are completely non-permissive for F-MuLV; this resulted in the generation of MSV(FeLV). Passage of this apparently pure FeLV pseudotype in cells permissive only for the replication of B-MuX surprisingly revealed residual murine xenotropic virus. It appears that pressure for survival resulted in genomic masking of B-MuX by heterologous virus envelopes. This phenomenon, which also occurs extensively in nature, implies that if absolute oncovirus genetic purity is required, even extensive attempts at purification may be inadequate.

Selective host range restriction of goat cells for recombinant murine leukemia virus and feline leukemia virus type A.

We isolated a strain of normal goat fibroblasts which was uniquely selective in that it allowed the replication of xenotropic murine leukemia virus but not polytropic recombinant murine leukemia virus. In addition, feline leukemia virus type A replication was severely diminished in these goat cells, whereas feline leukemia virus type B and feline endogenous RD114-CCC viruses replicated efficiently. No other known cells exhibit this pattern of virus growth restriction. These goat cells allow the study of xenotropic murine leukemia virus in mixtures which also contain recombinant murine leukemia virus and may be helpful in eliminating feline leukemia virus type which often coexists in feline sarcoma or leukemia virus mixtures with other feline leukemia virus types.

Genomic masking of nondefective recombinant murine leukemia virus in Moloney virus stocks.

HIX virus cloned from Moloney leukemia virus stocks is a nondefective, leukemogenic, and amphotropic murine oncornavirus with a recombinant-type major glycoprotein. Although Moloney leukemia virus stocks generally contain little or no free amphotropic virus, dilution analysis of several virus stocks and the examination of virus progeny from individual foci revealed that HIX virus is present and functionally coated with ecotropic Moloney virus envelopes. Because most mice have serum factors that inactivate recombinant viruses, masking may represent a general survival mechanism for HIX as well as other analogous recombinant viruses.

Identification of virus found in mouse lymphomas induced by HIX murine oncornavirus.

Lymphomas induced by pure HIX murine leukemia virus in two mouse strains contained large amounts of virus with amphotropic properties. Analysis of tumor derived virus purified by limiting dilution techniques indicated that its interference and neutralization spectra were essentially identical to parental HIX virus and different from eco- and xenotropic viruses. Examination of virus progeny from many individual foci induced by virus derived directly from lymphomas indicated that each infectious unit contained only HIX virus. No evidence of ecotropic virus presence was observed.

Two levels of restriction by mouse or cat cells of murine sarcoma virus coated by endogenous xenotropic oncornavirus.

Mouse and cat cells were each examined for the mode of restriction of endogenous xenotropic oncornavirus. Murine xenotropic helper virus (MuX) and its pseudo-type of Moloney murine sarcoma virus (MSV(MuX)) were grown in cat cells to high titre. MuX alone did not replicate in any mouse cell tested including normal or transformed outbred Swis 3T3 cells or SC-I cells, but did grow in a variety of other mammalian cells. MSV(MuX) was not able to achieve that intracellular state from which it could be rescued by mouse leukaemia virus (MuLV) in any mouse cell tested with the exception of SC-I cells. Detection of MSV(MuX) foci with appropriate helper virus was as sensitive in SC-I cells as in the cells of several other species. Sequential passage of MSV(MuX) virus complex in SC=I cells resulted in a loss of infectious sarcoma and helper viruses, but transformed, MSV rescuable cells were retained. If cat embryo cells were infected with either the feline endogenous xenotropic virus (FeX) or its MSV pseudotype (MSV(FeX), two analogous states of restriction were observed. FeX alone did not replicate in cat cells as measured by release of progeny virus or by FeX group-specific antigen induction. Cat cells could be susceptible or insusceptible to the entry of MSV(FeX) as measured by MSV rescue with appropriate ecotropic feline leukaemia virus. The sensitivity of detection of MSV(FeX) foci in some cat cells in the presence of feline ecotropic virus was comparable to that exhibited by cells of other mammalian species. A single strain of cat cells underwent a change in its restrictive capacity for MSV(FeX) on prolonged passage. Late passage cat cells became very insusceptible to MSV(FeX) but not to other pseudotypes of MSV. Infectious FeX or its group-specific antigens were not detected in the insusceptible cells. The major glycoprotein of FeX did appear as a surface antigen of the insusceptibel cells. It is apparent that two levels of cellular restriction can be distinguished in each of two mammalian cell systems by the susceptibility to penetration of MSV coated with endogenous xenotropic oncornavirus.

Simple, quantitative assay for both xenotropic murine leukemia and ecotropic feline leukemia viruses.

A cat cell line carrying the genome of a murine sarcoma virus developed discrete foci in linear response to infection with feline leukemia virus or xenotropic murine C-type virus.