PubMed Health⌕ Search

Biomedical subjects

K J Lewis

Publications and source records attributed to K J Lewis.

11 recordsLinked to original sources
PubMed1998

Estrogen receptor mutations.

The purpose of this paper is to review potential novel functional pathways by which estradiol and estrogenic compounds elicit biological responses in mammals. We will limit our approach to those novel functions suggested by phenotypes associated with estrogen receptor-alpha (ER alpha) gene mutations and polymorphisms. The study of these pathways has been greatly aided by the availability of ER alpha-minus mice, which lack classic biological responses to estradiol. In addition, the availability of an ER alpha-minus human family, aromatase-minus human families, and in the near future an aromatase-minus mouse model will allow correlations of novel phenotypes with the lack of active ER alpha protein. The ER alpha-minus mice can potentially be used to characterize in depth novel clinical phenotypes that link the functions of estrogens with sexual maturation, cardiovascular disease, osteoporosis, diabetes, and cancer.

Animals↗
PubMed1998

Development of a sustained-release biodegradable polymer delivery system for site-specific delivery of oligonucleotides: characterization of P(LA-GA) copolymer microspheres in vitro.

Development of a Sustained-Release Biodegradable Polymer Delivery System for Site-Specific Delivery of Oligonucleotides: Characterization of P(LA-GA) Copolymer Microspheres In Vitro Antisense oligodeoxynucleotides (ODNs) can selectively inhibit individual gene expression provided they gain access to and remain stable at the target site for a sufficient period of time. Biodegradable sustained-release delivery systems may facilitate site-specific delivery and also prevent degradation of ODNs by nucleases whilst delivering the nucleic acid in a controlled manner to the desired site of action. In this study, we have characterized biodegradable poly (lactide-co-glycolide) (P(LA-GA)) 50:50 microspheres for the potential delivery of antisense oligonucleotides in vivo. Phosphodiester (PO) oligonucleotides complementary to either c-myc proto-oncogene or the tat gene in HIV-RNA were adequately incorporated within P(LA-GA) microspheres with entrapment efficiencies up to 60% depending on particles size. In vitro release profiles of antisense nucleic acids from 10-20 microm size microspheres over 56 days in physiological buffer were triphasic. Profiles were characterised by an initial burst effect during the first 48 hours (phase 1) of release followed by a more sustained release (phase 2) with an additional increased release (phase 3) being observed after 25 days which corresponded with bulk degradation of the copolymer matrix. The release profiles were influenced by microsphere size, copolymer molecular weight, ODN loading, ODN length and by the pH of release medium used. The serum stability of PO ODNs was significantly improved when entrapped within P(LA-GA) microspheres and the hybridization capability, as assessed by duplex melting (Tm) measurements, of released ODN was not impaired by the double-emulsion microsphere fabrication procedure used. Thus, P(LA-GA) microspheres appear to be promising candidates for improving site-specific delivery profiles for ODNs and are worthy of further evaluation in vivo.

Base Sequence↗
PubMed1988

The lipolytic activity of low concentrations of insulin-like growth factors in ovine adipose tissue.

Insulin-like growth factor I (IGF-I) at concentrations of 40 ng/ml is lipogenic in ovine adipose tissue slices in vitro. Neither human IGF-II (hIGF-II) or rat IGF-II (rIGF-II) [multiplication-stimulating activity (MSA)] is lipogenic at similar concentrations. However, when present at lower concentrations recombinant human IGF-I (rhIGF-I) (400 pg/ml), hIGF-II (0.4 pg/ml), and MSA (40 pg/ml) were lipolytic. As IGF-II appeared more potent than IGF-I in promoting lipolysis, this effect may be mediated via the type 2 IGF receptor. The lipolytic effect of GH may be partly due to the actions of IGFs released locally.

Adipose Tissue↗
PubMed1981

Residual formaldehyde in dialyzers: quantity, location, and the effect of different methods of rinsing.

When formalin-sterilized dialyzers were rinsed by our standard technique (similar to that used in many other dialysis centres) undesirable concentrations of formaldehyde were found in the dialyzers at the start of dialysis. When the technique was modified by passing part of the saline through the blood compartment immediately before connection and discarding the saline left in the dialyzer at the time of connection, the concentration of formaldehyde infused into the patient fell below 2 micrograms/ml. However, the dialyzers still contained up to 13 mg of formaldehyde which leached slowly from the dialyzer during simulated dialysis. Some residual formaldehyde was found in several components of the dialyzer but the great majority was contained in the cellulose membrane.

Disinfectants↗
PubMed1981

Formation of anti-N-like antibodies in dialysis patients: effect of different methods of dialyzer rinsing to remove formaldehyde.

Use of formalin to sterilize dialyzers is known to be responsible for the formation of anti-N-like antibody in long-term hemodialysis patients. Patients dialyzed as in-patients using formalin were found to be completely free of anti-N-like antibody, while among those on home dialysis, there was a high prevalence (31%) and incidence. The hospital patients were found to be receiving concentrations of formaldehyde less than 1 microgram/ml while those on home dialysis received 3-13 micrograms/ml. This is offered as an explanation for the absence of anti-N-antibody in patients using formalin-sterilized dialyzers.

Antibodies, Anti-Idiotypic↗
PubMed1978

Efficacy of trivalent inactivated encephalomyelitis virus vaccine in horses.

Twenty-nine horses were vaccinated with a trivalent (Venezuelan, eastern, and western) inactivated equine encephalomyelitis virus vaccine. The vaccine purchased for this study was the only one licensed and commercially available in May, 1975. Plaque-neutralizing and hemagglutinin-inhibiting antibodies in response to each of the 3 equine encephalomyelitis viruses were determined after vaccination. Horses had rising levels of plaque-neutralizing and hemagglutinin-inhibiting antibodies shortly after injection with the 1st and 2nd doses of the vaccine (given 3 weeks apart) and were refractory to challenge of immunity with virulent homologous virus at 3, 8, and 12 months after vaccination. After 12 months, 8 horses were revaccinated; maximum antigenic stimulation was achieved with the 1st dose of the 2nd series of vaccinations.

Animals↗
PubMedDate not supplied

Evaluation of the therapeutic efficacy of some antimuscarinics against soman in vivo.

The therapeutic efficacy of tacrine, atropine and glycopyrrolate alone or in combination with the oxime HI-6 against soman was evaluated in anaesthetized rats. Arterial blood pressure, heart rate, respiratory frequency and body temperature were monitored in vivo. Blood cholinesterases were determined after each drug or soman challenge. At the lowest concentration tested (2.5 mg kg-1), tacrine was effective in improving the survivability of the rat by a factor of 2.6 (protection ratio), whereas the protection by atropine or glycopyrrolate was either insignificant or only marginally effective (protection ratio ranged from 1.0 to 1.9). In combination with HI-6, atropine increased the ratio to 4.6. In contrast, tacrine with HI-6 failed to improve the efficacy of the regimen, while glycopyrrolate plus HI-6 showed only slight improvement. The four physiological parameters monitored were relatively constant during the time course of the experiment in both the control and those with drug therapy. The more noticeable changes occurred toward the end of the experiment when sufficient amount of soman was injected to cause lethality. Death of the animal was usually preceded by a surge of arterial blood pressure and heart rate and a decrease in respiratory frequency. These physiological parameters rapidly deteriorated to zero just before the animal died. Blood and plasma cholinesterases were significantly inhibited after the animal received a relatively small dose of soman (20 micrograms kg-1) and were almost completely inactivated after the lethal dose of soman was administered. However, these changes of enzyme activity did not correspond well with the survivability of the rat. The inclusion of HI-6 with the three antimuscarinics appeared to be capable of protecting some cholinesterases against soman.

Acetylcholinesterase↗