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Biomedical subjects

J Haslam

Publications and source records attributed to J Haslam.

17 recordsLinked to original sources
PubMed1995

STAT protein complexes activated by interferon-gamma and gp130 signaling molecules differ in their sequence preferences and transcriptional induction properties.

Activation of members of the STAT (signal transducers and activators of transcription) family of latent transcription factors is an early event following the binding of many cytokines to their cognate receptors. Although the patterns of STATs activated by different cytokines are well described, the consequences of differential STAT activation are less well studied. We show by mutational analysis that STAT binding elements (SBEs) exist that discriminate between STAT complexes containing STAT1 alpha, STAT3 or both, and that these elements show altered cytokine responsiveness. We also show that in the context of a minimal promoter, single and multiple SBEs exhibit strikingly different patterns of transcriptional activation in response to IFN-gamma, IL-6, OSM or LIF. These differences in transcriptional activation are correlated with the differential ability of these cytokines to activate STAT1 alpha, STAT3 or both. Our results show that the pattern of STATs activated by a cytokine and the arrangement and sequence of the SBEs in the responding promoter have a profound effect on the ability of the cytokine to elicit a transcriptional response.

Animals↗
PubMed1994

Examination of fetuses after induced abortion for fetal abnormality--a follow-up study.

In the North-Western Region we offer a service to examine fetuses aborted after the diagnosis of fetal abnormalities. Many obstetricians use this service. We examined 343 mid-trimester fetuses over the last 5 years: 215 following an abnormal scan and 128 abnormal amniotic fluid or villus findings. When necessary, investigations were performed. A post-mortem examination was always required. As a result of fetal investigation, the scan diagnosis was modified or refined in 91 cases (42.3 per cent). In three of these cases no fetal abnormality was found. For the fetuses diagnosed as abnormal by amniocentesis or chorionic villus biopsy, in one (0.8 per cent) the pre-termination diagnosis was not confirmed. The results were similar to those of our previous 5-year study except (a) diagnosis of neural tube defects was rarely based on amniocentesis in the present study (2/62, 3.2 per cent) compared with the previous one (32/103, 31 per cent), and (b) renal abnormalities were more often diagnosed in the pre-termination scan in the present study. We conclude that the examination of aborted mid-trimester fetuses by dysmorphologists continues to improve diagnosis, allowing more accurate genetic counselling for the families.

Abortion, Induced↗
PubMed1994

Rapid activation of the interferon-gamma signal transduction pathway by inhibitors of tyrosine phosphatases.

Induction of gene expression by interferon-gamma involves the activation of a latent cytoplasmic transcription factor, p91, by phosphorylation on a single tyrosyl residue. This phosphorylation triggers dimerization, nuclear translocation, and the binding of p91 to interferon-gamma response elements present in the promoters of induced genes. Phosphorylation of p91 requires the activation of two tyrosine kinases, JAK1 and JAK2, that themselves become phosphorylated on tyrosyl residues shortly after interferon-gamma binds to its receptor. The importance of tyrosine phosphorylation in this pathway prompted us to investigate the role of protein tyrosine phosphatases in the regulation of the pathway. We find that in the absence of interferon-gamma, treatment of cells with an inhibitor of tyrosine phosphatases causes a rapid and potent activation of the components of the interferon-gamma signal transduction pathway and induces an interferon-gamma-responsive gene. This suggests that tyrosine phosphatases act both to repress the interferon-gamma signal transduction pathway in the absence of interferon-gamma and to downregulate the pathway after interferon-gamma induction.

Base Sequence↗
PubMed1993

46,XY/47,XY, + 17p + mosaicism in amniocytes associated with fetal abnormalities despite normal fetal blood karyotype.

46,XY/47,XY, + 17p + mosaicism was found in two primary amniotic fluid cultures (AFCs). Fetal blood karyotype was normal, but ultrasonography revealed Dandy-Walker malformation and bilateral choroid plexus cysts. Following termination of pregnancy, fetal examination revealed post-axial polydactyly and neuroblastoma-in-situ affecting both adrenals in addition to the cerebellar abnormalities. Mosaicism for the aberrant cell line was confirmed in all fetal tissues sampled and in the placenta.

Abnormalities, Multiple↗
PubMed1992

Fetus with unbalanced translocation involving chromosomes 2 and 11.

We report a fetus with an unbalanced translocation between chromosomes 2 and 11, the product of a paternal balanced reciprocal translocation, fetal karyotype 46, XX, -11, +der(11)t(2;11) (q35;q24.1)pat. The fetus had unusual facial features. The relevance of this case to mapping of the type I Waardenburg syndrome gene is discussed.

Abnormalities, Multiple↗
PubMed1986

Cadmium-induced changes in renal hemodynamics in the domestic fowl.

Low i.v. doses of cadmium chloride (15 micrograms Cd) given to pullets resulted in a significant reduction in urine flow (UF), glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). However, in hens treated with the heavy metal chelate FeNa EDTA prior to cadmium treatment no oliguria or reduction in GFR or ERPF was observed. It is suggested that the renal changes following the i.v. administration of cadmium to diuretic hens and alleviated in hens primed with the heavy metal chelate may result from changes in glomerular hemodynamics.

Animals↗
PubMed1984

Acyloxyamines as prodrugs of anti-inflammatory carboxylic acids for improved delivery through skin.

An N,N-dialkylhydroxylamine derivative of indomethacin has been synthesized. It has been shown to improve the delivery of indomethacin through mouse skin (compared to indomethacin itself) by a factor of two, to be more effective than indomethacin in inhibiting thermal inflammation (two to three times) in animal models, but to be only as effective as indomethacin in inhibiting UV-B radiation erythema in human volunteers.

Administration, Topical↗
PubMed1978

Enhancement of bioavailability of a hydrophobic amine antimalarial by formulation with oleic acid in a soft gelatin capsule.

The relative availability of the orally administered hydrophobic antimalarial alpha-(dibutylaminomethyl)-6,8-dichloro-2-(3',4'-dichlorophenyl)-4-quinolinemethanol (I) from two dosage forms was determined in beagle dogs. Compound I was soluble in oleic acid to the extent of 23.5% (w/w), and oleic acid was suitable for encapsulation in soft gelatin capsules. The availability of I formulated as its hydrochloride salt in a standard hard gelatin capsule formulation was significantly lower than that of I formulated in a soft gelatin capsule with oleic acid as the solvent. A 20% solution of I in oleic acid (soft gelatin capsules) maintained at 23 degrees provided 4% of the oleic acid ester of I iwithin 1 month. Further reaction, however, was not seen over 2 years.

Animals↗
PubMed1975

Photolytic degradation of alpha-[(dibutylamino)methyl]-6,8-dichloro-2-(3',4'-dichlorophenyl)-4-quinoline methanol: an experimental antimalarial.

A study of the effects of various storage conditions on the rate and products of degradation of the quinoline methanol antimalarial agent, alpha-[(dibutylamino)methyl]-6,8-dichloro-2-(3',4'-dichlorophenyl)-4-quinoline methanol, was undertaken. The degradation was followed by high-pressure liquid chromatography and TLC in oxygenated and deoxygenated methanol, ethanol, chloroform, and chloroform-heptane mixtures under UV and laboratory fluorescent lighting irradiation, as well as in the absence of light. The kinetics of degradation confirmed the major catalyzing factor to be UV irradiation. The compound was stable in the absence of light and reasonably stable under fluorescent lighting both in the presence and absence of oxygen. The degradation resulted in a major product, 6,8-dichloro-2-(3',4'-dichlorophenyl)-4-quinoline-carboxaldehyde, whose structure was confirmed by elemental analysis and IR, NMR, and mass spectral data.

Antimalarials↗
PubMed1972

Effects of exteriorization of the ureters on the water metabolism of the domestic fowl.

1. Six domestic fowls were operated for exteriorization of the ureters.2. Three weeks after the operation their food and water intake was compared with that of six unoperated control fowls of similar weight.3. Water intake was calculated from the amount of water drunk, the metabolic water and the water content of the food eaten; while water loss was estimated from the water content of urine and faeces excreted and from evaporation.4. Fowls with exteriorized ureters drank more than the control birds. The excess of water drunk by these birds approximated the amount of water lost in the urine.

Animals↗
PubMed1966

Water diuresis in the domestic fowl.

1. The exteriorization of ureters in domestic fowls allows the collection of urine uncontaminated by faeces.2. When water is administered by stomach tube to a fowl, water is stored in the crop, from which it is slowly released into the proventriculus.3. Immediately after water gavage, there is a sharp rise of urine flow accompanied by an increase in endogenous creatinine excretion and a fall in the osmolarity of the urine. This initial increase in urine flow is of short duration, and is followed by a normal curve of diuresis with a peak at about 90 min after hydration.4. The first rise in urine flow following the filling of the crop appears to be of reflex origin, as distension of the crop with paraffin produces an enhanced excretion of urine and of creatinine.5. Changes in urine flow and in creatinine excretion are closely correlated.6. After water deprivation for 18 hr, the urine is slightly hyptertonic to blood. The maximum urine concentration observed was of the order of 600 m-osmole/l.

Animals↗
PubMed1966

The effects of urea and hydrochlorothiazide on the renal functions of rat and domestic fowl.

1. Rats and domestic fowls were given by stomach tube water, urea and hydrochlorothiazide, alone or in combination, in the following amounts: water, 5 ml./100 g; urea, 4 ml. of 1.5% solution + 1 ml. water/100 g; hydrochlorothiazide, 4 ml. of 1.5% urea solution + 1 ml. containing 0.1 mg hydrochlorothiazide/100 g.2. The onset of water diuresis was faster in the fowl than in the rat. It was accompanied by a lower rate of excretion of osmotically active solutes in the former than in the latter. The rate of excretion of creatinine in rats was fourfold that in birds.3. After urea administration, the amount of urea excreted by the fowl was about one fifth that excreted by the rats. While urea produced in rats an osmotic diuresis, with enhanced excretion of osmotically active solutes, in birds it had little effect on either urine flow or solutes excretion.4. Administration of hydrochlorothiazide in rats produced a moderate antidiuresis accompanied by a marked increased excretion of Na and K; in birds, a small increase in the excretion of Na and K but no effect on the urine flow.5. The differences observed between rats and birds can be attributed to the poor development of filtration rate and the absence of a well developed counter-current system in the fowl.

Animals↗
PubMedDate not supplied

Floor plan.

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Female↗