Identification and characterization of three new alternatively spliced mu-opioid receptor isoforms.

We have identified four new mu-opiod receptor (MOR)-1 exons, indicating that the gene now contains at least nine exons spanning more than 200 kilobases. Replacement of exon 4 by combinations of the new exons yields three new receptors. When expressed in Chinese hamster ovary cells, all three variants displayed high affinity for mu-opioid ligands, but kappa and delta drugs were inactive.

A vision for ambulatory care in the 21st century.

The 1990's have been a remarkable decade for ambulatory care providers. Ambulatory care services have flourished in an era of rapidly increasing demands and seemingly limitless potential. Will the first decade of the next millennium continue this trend or is something new on the horizon? Ambulatory care's future prospects need to be evaluated within the context of the overall health care delivery environment of the future.

Antisense mapping KOR-1: evidence for multiple kappa analgesic mechanisms.

In binding assays, both dynorphin B and alpha-neoendorphin are relatively selective for the kappa1b site, unlike U50,488H which has high affinity for both kappa1a and kappa1b sites. In vivo, U50,488H, dynorphin B and alpha-neoendorphin analgesia are reversed by the kappa1-selective antagonist, nor-binaltorphimine (norBNI). Antisense mapping the three exons of KOR-1 revealed that probes targeting all three exons blocked U50,488H analgesia, as expected.

Intrafamilial relations of cardiovascular disease risk factors in African-Americans: longitudinal results from DC SCAN.

Background: Few studies have examined intrafamilial patterns of cardiovascular disease (CVD) risk factors in African-American families or identified potential influences on these patterns. This study examines the effects of age and sex of child on correlations between siblings during childhood as well as between mothers and their offspring in African-American families at two points in time.

Methods: CVD risk factors were assessed in a sample of 267 pairs of African-American siblings and their mothers.

Role of aldosterone in renal vascular injury in stroke-prone hypertensive rats.

Stroke-prone spontaneously hypertensive rats (SHRSP) on 1% NaCl drinking solution and Stroke-Prone Rodent Diet develop severe hypertension and glomerular and vascular lesions characteristic of thrombotic microangiopathy seen in malignant nephrosclerosis. We recently reported that spironolactone, a mineralocorticoid receptor antagonist, markedly reduced proteinuria and malignant nephrosclerotic lesions in these animals. This observation, together with our previous findings that angiotensin-converting enzyme inhibitors prevent the development of vascular damage, suggests that mineralocorticoids, as part of the renin-angiotensin-aldosterone system, play a pathophysiological role in this model.

Mitogen-activated protein kinase-dependent and protein kinase C-dependent pathways link the m1 muscarinic receptor to beta-amyloid precursor protein secretion.

Full and functionally selective M1 muscarinic agonists (carbachol and AF102B, respectively) activate secretion of the soluble form of amyloid precursor protein (APPs) in PC12 cells expressing the m1 muscarinic receptor (PC12M1 cells). This activation is further augmented by neurotrophins such as nerve growth factor and basic fibroblast growth factor. Muscarinic stimulation activates two transduction pathways that lead to APPs secretion: protein kinase C (PKC)-dependent and mitogen-activated protein kinase (MAPK)-dependent pathways.

Silver-stained nucleolar organizer regions (AgNORs) as a prognostic value in malignant melanoma.

The nucleolar organizer regions (NORs) are chromosomal loops of DNA and proteins involved in ribosomal synthesis. By silver staining, they can be identified as black dots (AgNORs) in the nuclei. Their size and number reflect cell and nuclear activity.

Identification and differential regional expression of KOR-3/ORL-1 gene splice variants in mouse brain.

KOR-3, also known as ORL-1, is a member of the opioid receptor family, encoding the murine receptor for orphanin FQ/nociceptin. In the current studies we have identified five different splice variants of KOR-3 in mouse brain, three of which have not been previously reported. In addition to variants with a 15 bp deletion at the 3'-end of the first coding exon (KOR-3d) and an 81 bp insertion between the second and third coding exons (KOR-3e), three new variants with insertions of 34 (KOR-3a), 98 (KOR-3b), and 139 bp (KOR-3c) between the first and second coding exons have been obtained.

Contraception in the patient with liver disease.

Selection of a method of contraception in patients with liver disease can be complicated. Tubal ligation should be considered in the setting of chronic liver disease for those patients who have completed families. Multiple reversible methods of contraception are currently available but may affect hepatic disease.

Cloning and characterization of a mouse sigma1 receptor.

A cDNA clone (S2-1a) isolated from a mouse brain cDNA library, using a guinea pig sigma1 cDNA as probe, has high homology to the predicted protein sequence of the guinea pig (88%) and human (90%) sigma1 receptors. Northern analysis revealed a major mRNA of approximately 1.8 kb in a wide range of mouse tissues, with highest levels in brain, liver, kidney, and thymus.

Mineralocorticoid blockade reduces vascular injury in stroke-prone hypertensive rats.

Chronic treatment of saline-drinking stroke-prone spontaneously hypertensive rats (SHRSP) with agents that interfere with the formation or actions of angiotensin II (Ang II) prevents the development of stroke and renal vascular damage. Ang II, in addition to its direct vascular effects, stimulates the synthesis and release of aldosterone. To assess the role of aldosterone in the development of pathologic changes in these rats, we implanted time-release pellets containing 200 mg of the mineralocorticoid receptor antagonist, spironolactone, into 14 SHRSP at 7.

Regional renal nitric oxide release in stroke-prone spontaneously hypertensive rats.

Diminished nitric oxide (NO) production has been implicated in the pathogenesis of salt-sensitive hypertension. We questioned whether such a defect is responsible for the malignant hypertension and nephrosclerosis in stroke-prone spontaneously hypertensive rats (SHRSP) fed a high-salt/stroke-prone diet (S) versus a regular diet (R). NO release from 30-minute incubates of cortex and outer and inner medulla were studied in SHRSP at 10, 12, and 16 weeks of age on the S diet versus R diet.

Faculty practice and university hospital integration.

With a long history as unique providers of health care, academic medical centers have been exempt from many of the troubles plaguing less distinguished health care organizations. But with the increasing dominance of managed care, academic medical centers are facing fierce competition from aggressive and often better organized providers. Burdened with cumbersome and tradition-laden organization structures and volatile turf issues, many academic medical centers are still in the early stages of collaborating with physicians and other providers to develop the care continuums being demanded by payors.

Catholic healthcare's future. Ten models for competition and capitation.

In the next five years, Catholic providers must select strategies that will involve affiliations, acquisitions, and consolidations with Catholic and non-Catholic partners. At least 10 options are available to meet the long-term trends of managed care, competition, and capitation. Vertical integration allows comprehensive patient care.

Early appearance of neutralizing antibodies after vaccination with an inactivated hepatitis A vaccine.

Sera from 30 subjects vaccinated with the Pasteur Merieux Serums & Vaccins (PM) inactivated hepatitis A vaccine, and from 30 subjects vaccinated with the Smithkline Beecham (SB) inactivated hepatitis A vaccine, were tested in two laboratories in order to provide comparative data on neutralizing activities of vaccine-induced antibodies. Sera were also evaluated by a modified radioimmunoassay (mRIA) and results were compared to neutralization assays results. Neutralizing antibody titres provided by the two laboratories correlated well (coefficient or correlation 0.

Estrogen, progesterone and testosterone receptors in human fetal cartilaginous tissue: immunohistochemical studies.

Computerized image analysis was used to study the distribution in cartilage of receptors to estrogen, progesterone, and testosterone during human fetal development. We have examined three histologically distinct cell groups (hypertrophic, proliferating, and reserve zones) in long bones, vertebrae, and trachea from 19 fetuses. Comparisons were made across gender and gestational age.

Rightsizing the delivery system.

In the next five to 10 years, managed care penetration in large metropolitan areas and small cities could reach 90 percent, while per-member-per-month premium payments could fall to an average of $100. At the same time market demand for acute care services is expected to decline, and demand for subacute and nonacute care services will rise sharply. Most health systems are not configured to meet these emerging market demands.

Immune response to a new hepatitis B vaccine in healthcare workers who had not responded to standard vaccine: randomised double blind dose-response study.

Objective: To evaluate the immunogenicity and reactogenicity of a new triple S recombinant hepatitis B vaccine in a cohort of healthy people in whom currently licensed hepatitis B vaccines had persistently not induced an immune response.

Design: Single centre, randomised, double blind, dose-response study.

Setting: Research vaccine evaluation centre at a teaching hospital.