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Biomedical subjects

J E Beach

Publications and source records attributed to J E Beach.

17 recordsLinked to original sources
PubMed2001

Clinical trials integrity: a CRO perspective.

When contract research organizations (CROs) were first formed, pharmaceutical companies outsourced to them only certain aspects of the conduct of their clinical trials. At first CROs were highly specialized entities, providing, for example, either biostatistical advice, clinical research associates who monitored investigational sites for regulatory compliance, or regulatory support. Gradually, full service CROs emerged, offering a full range of services for clinical trials, including the selection of investigators and investigational sites, assistance with patient recruitment, safety surveillance and reporting, site audits, and data management and biostatistics. This evolving relationship between CROs and the pharmaceutical and medical device industries has resulted in CROs assuming more and more of the regulatory and ethical risks and responsibilities inherent in the conduct of clinical trials. In this full service role, CROs, unlike sponsors, are not interested in the outcome of study, but like sponsors, are subject to heavy regulation by the federal government, must follow applicable state laws, must respect international guidelines, and are obliged to follow their own operating procedures. Moreover, they are judged by the industry on the basis of the scope and quality of services provided, including the degree of adherence to the research protocol, regulatory requirements, and timelines; the quality of the professional working relationships with investigators and institutions, both academic and community-based; and the validity of the data. Further, CROs are subject to comprehensive audits by sponsoring companies, FDA, and other regulatory authorities. For all these reasons, CROs are being tasked with strict vigilance of all stages of the clinical trial process to ensure that the laws, regulations, and industry standards designed for the protection of human subjects and data integrity are maintained.

Advisory Committees↗
PubMed1993

Spontaneous neoplasia in the ferret (Mustela putorius furo).

Thirteen spontaneous tumours in ferrets from two laboratory breeding colonies are described, including two types not previously reported in this species, namely, uterine teratoma and neurilemmoma. The literature on tumours in laboratory and domestic ferrets is comprehensively reviewed from the first reported case in 1950. Only 20 cases were reported from 1950 to 1979, nearly all from laboratory or zoological collections. In the following 10 years more than 170 further cases were reported, about half of them in domestic pet ferrets. A review of the limited literature on tumours in related species reveals substantial incidences in black-footed ferrets and ranch mink allowed to live out their lifespan, and isolated cases in polecats and at least eight other species of Mustelidae.

Animals↗
PubMed1989

Rapid release of multiple hormones from rat pituitaries perifused with recombinant interleukin-1.

Previous studies demonstrated a direct action of interleukin-1 (IL-1) on release of hormones from rat anterior pituitary cells in monolayer culture. To rule out any possibility of a paracrine effect from the elevated hormones in the static monolayer system, and to examine further the dynamics of hormone release elicited by IL-1, studies were conducted with rat anterior pituitary tissue in a computer-controlled automated perifusion system. In experiments performed on the same day as sacrifice, IL-1 stimulated the release of adrenocorticotrophic hormone (ACTH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), growth hormone (GH) and prolactin (PRL) in a dose-related manner. Peak levels were achieved within 6 minutes of exposure to IL-1. However, PRL was not increased over the baseline fluctuations when pituitaries were perifused with IL-1 after 72 hours of incubation. Hormone release did not appear to undergo desensitization after multiple short pulses of IL-1. Heat-denatured IL-1 had no effect on hormone release. The rapid response suggests that IL-1 acts acutely to release preformed hormone stores.

Animals↗
PubMed1988

Reversal of inhibition of prolactin secretion in cultured pituitary cells by muscarinic antagonists.

We investigated whether the inhibition of prolactin secretion from pituitary cells by carbachol, a cholinergic agonist resistant to hydrolysis by cholinesterases, would be a useful bioassay to explore an important nonneuronal action of antimuscarinic agents. Carbachol inhibited prolactin secretion from cultured rat anterior pituitary cells in a dose-dependent manner with a mean IC50 of 1.5 +/- 0.6 (S.E.) microM and maximal inhibition at 10(-5) M. Prolactin levels in media were significantly reduced by 30 min of incubation with carbachol. This inhibition persisted for 24 hr and was reversed by 2 microM atropine. The stimulation of prolactin secretion by 10(-6) M thyrotropin releasing hormone (to 1.5 times control) was inhibited by the addition of carbachol (10(-5) M). Addition of atropine (2 microM) to these agents restored maximal stimulation by thyrotropin releasing hormone. The inhibition of carbachol by atropine was competitive, whereas the inhibition of thyrotropin releasing hormone by carbachol was noncompetitive. The apparent affinities (Ki) of several antimuscarinic agents in pituitary cells were determined by their ability to reverse the carbachol inhibition of prolactin secretion: atropine 0.14 nM, scopolamine 0.26 nM, azaprophen 0.3 nM, aprophen 3.0 nM, pirenzepine 42 nM, benactyzine 80 nM and adiphenine 198 nM. These potencies correlated positively with those previously determined for inhibition of alpha amylase secretion from pancreatic acinar cells as well as with those for behavioral depressant actions of the antimuscarinics. Cultured anterior pituitary cells thus provide an effective system for testing the relative potencies of muscarinic antagonists in pituitary cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Release of multiple hormones by a direct action of interleukin-1 on pituitary cells.

Exposure to bacterial endotoxins has long been known to stimulate the release of anterior pituitary hormones; administration of endotoxin was at one time a common clinical test of anterior pituitary function. Endotoxin is a potent stimulus for production of the endogenous pyrogenic protein, interleukin-1 (IL-1), by macrophages and monocytes. The possibility that IL-1 has a direct effect on the secretion of hormones by rat pituitary cells in a monolayer culture was investigated. Recombinant human IL-1 beta stimulated the secretion of adrenocorticotropic hormone, luteinizing hormone, growth hormone, and thyroid-stimulating hormone. Increased hormone secretion into culture supernatants was found with IL-1 concentrations ranging from 10(-9) M to 10(-12) M. Prolactin secretion by the monolayers was inhibited by similar doses. These concentrations of IL-1 are within the range reported for IL-1 in serum, suggesting that IL-1 generated peripherally by mononuclear immune cells may act directly on anterior pituitary cells to modulate hormone secretion in vivo. Incubation of IL-1 solutions with antibody to IL-1 neutralized these actions. These pituitary effects of IL-1 suggest that this monokine may be an important regulator of the metabolic adaptations to infectious stressors.

Adrenocorticotropic Hormone↗
PubMed1985

Microplate solid-phase radioimmunoassay for rat prolactin.

A rat prolactin solid-phase radioimmunoassay has been developed that uses 96-well microtiter plates with removable wells to which the antibody is firmly adsorbed, resulting in a solid-phase antibody. Antigen as either reference or unknown competes with radioactivity labeled antigen for binding sites on the solid-phase antibody. After immunoreaction, free antigen is removed by washing the wells with phosphosaline solution. The solid-phase antibody-antigen complex is counted for quantitation with data reduction methods currently used in routine radioimmunoassay procedures. This microplate solid-phase radioimmunoassay has several advantages over conventional methods without sacrificing specificity, sensitivity, or accuracy. This method is rapid, compact, economical, easily automated, and could be readily established in other laboratories.

Animals↗
PubMed1982

The ferret for non-rodent toxicity studies - a pathologist's view.

Ferrets have been used in our laboratories over the past 4 years in 12 small drug toxicity studies (14-28 days, 6-8 ferrets, usually male) and recently for a larger study (90 days, 54 ferrets). This has provided a basis for assessing the suitability of the ferret as an alternative species for non-rodent drug toxicity studies. It is amenable to daily dosing by gavage, and it shows gastric damage of a similar type and degree to the dog in response to oral non-steroidal anti-inflammatory drugs. Certain minor peculiarities of its background pathology are worth noting, but no major problems were seen in this area which would limit its usefulness for routine toxicity testing.

Animal Diseases↗
PubMed1975

Serum prolactin and LH in early phases of delayed versus direct pseudopregnancy in the rat.

Delayed or direct pseudopregnancies were induced by electrical stimulation of the cervix at 1400 h on diestrus day 2 (D-2) or on estrus, respectively. Blood samples for measurement of prolactin and LH by radioimmunoassay were collected by rapid decapitation at 5, 15, 30, 45 or 60 min after cervical stimulation or thereafter at 3-h intervals throughout the first 6 days of leukocytic vaginal smears of pseudopregnancy (PSP L-1 to L-6). For comparison, untreated animals were decapitated at the same 3-h intervals throughout the 4-day cycle. Serum LH concentrations in all the experimental animals did not vary from those measured in the cyclic controls. Compared with the normal cycle, prolactin (PRL) levels were not different until 10 h after cervical stimulation during estrus. After stimulation on D-2, PRL secretion did not differ from that in the normal cycle until approximately 37 h later, when there was a short rise following the usual proestrus surge. In both direct and delayed pseudopregnancy, twice-daily PRL surges appeared on L-1 and, except for a missing nocturnal surge on L-2 in delayed PSP, continued regularly through L-6. The absence of any immediate increase of PRL following the D-2 stimulus strongly supports the view that information from the stimulus is retained in the central nervous system to be expressed later after a set of new, competent corpora lutea has been formed.

Animals↗