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Biomedical subjects

J Carroll

Publications and source records attributed to J Carroll.

At least 145 records · Page 8Linked to original sources

Gear future training to practitioners' needs. Attitudes towards intravenous drug users.

1. There is no clear-cut relationship between staff knowledge and their attitudes to HIV and Aids. 2. Perceptions of service delivery to drug users are likely to be affected by respondents' occupational backgrounds. 3. The effectiveness of service delivery is likely to be affected by situational constraints. 4. There is a need for improved training and support, particularly for non-specialist staff.

Acquired Immunodeficiency Syndrome↗

Generalized pustular eruption associated with converting enzyme inhibitor therapy.

A 67-year-old man presented with a high fever and a generalized rash. His extended hospital stay was characterized by fever with repeated staphylococcal bacteremia and the appearance of axillary lymphadenopathy and splenomegaly. Skin lesions became hyperpigmented, dry, and atrophic with areas of exfoliation and uclers. Examination of skin and lymph node biopsy specimens showed findings consistent with mycosis fungoides. The patient unexpectedly recovered on discontinuation of captopril. A positive macrophage inhibiting factor response for both captopril and enalapril indicated that the non-sulfhydryl moiety was the antigenic stimulant for the lesion resembling mycosis fungoides.

Aged↗

Spinal cord lamina V and lamina VII interneuronal projections to sympathetic preganglionic neurons.

This light and electron microscopic study sought to localize spinal cord interneurons that contribute to the normal and abnormal physiological regulation of spinal sympathetic preganglionic function. Sympathetic preganglionic neurons in caudal C8 through T4 of rat spinal cord were retrogradely labeled with wheat germ agglutinin (WGA) and/or cholera beta subunit (CT beta) following injections into the superior cervical ganglion (SCG). With two exceptions, the observed locations of retrogradely WGA- and CT beta-labeled sympathetic preganglionic neurons were as expected from previous studies. The exceptions were restricted populations of cells in caudal C8 and rostral T1 spinal segments. These neurons were classified as ventrolateral (vlSPN) and ventromedial (vmSPN) sympathetic preganglionic neurons; their somata and dendrites encircled dorsolateral lamina IX motoneurons. Only WGA was transported transneuronally following the retrograde labeling of sympathetic preganglionic neurons. Transneuronally WGA-labeled spinal interneurons were located principally in the reticulated division of lamina V and dorsolateral lamina VII. A strict segmental organization was observed. All transneuronally labeled interneurons were ipsilateral to, and coextensive with, retrogradely WGA-labeled sympathetic preganglionic neurons. Electron microscopic observations suggested that retrograde transsynaptic passage of WGA occurred within the sympathetic preganglionic neuropil and showed further that similar classes of organelles were WGA immunoreactive in retrogradely labeled sympathetic preganglionic neurons and in transneuronally labeled lamina V and lamina VII neurons: 1) cisternae and vesicles at the trans face of the Golgi apparatus, 2) large endosomes/dense bodies, and 3) multivesicular bodies. The data are consistent with two hypotheses: 1) Somatic and visceral primary afferent inputs to thoracic spinal cord modify segmental sympathetic preganglionic function through activation of a disynaptic pathway involving lamina V and/or lamina VII interneurons, and 2) long-loop propriospinal pathways access sympathetic preganglionic neurons through symmetrical, segmental interneuronal circuitry.

Animals↗

Improved neurological outcome in children with chronic renal disease from infancy.

Progressive encephalopathy, developmental delay, microcephaly, electroencephalogram (EEG) and computed tomographic (CT) scan abnormalities have been reported in 80% of children with chronic renal failure (CRF) in infancy. Malnutrition, aluminium intoxication and psychosocial deprivation are proposed as causes. In 15 children with CRF from infancy we evaluated the effect of no aluminium salts and early vigorous nutritional and psychosocial support, in addition to the standard therapy, on neurological development. Six patients underwent dialysis (2 at birth) and 3 received transplants. None of our patients were given aluminium therapy. The nutritional status of the patients in the first 2 years of life was assessed with the waterlow classification. At the end of the follow-up period (mean 50 months range 14-148 months), patients underwent neurodevelopmental assessment, head CT scan, EEG, nerve conduction velocity (NCV) and auditory brain stem evoked response (ABER). None of our patients developed progressive encephalopathy or recurrent seizures. All have a normal neurological examination apart from hypotonia. Microcephaly was present in 5 patients. There was a good correlation between malnutrition in the first 2 years of life and microcephaly. Developmental delay was present in 3 patients; all 3 were microcephalic. There was evidence of brain atrophy on CT scan in only 3 patients. EEG was abnormal in 6 patients, but only severe in 1 patient. Only 1 patient had diminished NCV; all patients had a normal ABER. We conclude that a policy of no oral aluminium therapy and early nutritional support leads to better neurological outcome in children with CRF from infancy.

Brain Diseases↗

Hemodynamic and humoral effects of the angiotensin II antagonist losartan in essential hypertension.

Losartan (DuP 753) is a novel orally active angiotensin II antagonist that lowers blood pressure. The present study evaluates the hemodynamic and humoral effects of losartan in essential hypertension. Fifteen patients (12 men, 3 women; mean age, 46 +/- 2 years; range, 33 to 64 years) with a diastolic blood pressure (DBP) between 95 and 115 mm Hg after 2 weeks of placebo participated in the study. Initially the patients were treated with losartan (50 mg) once daily for 1 month. Then, if the trough DBP was > or = 93 mm Hg, hydrochlorothiazide (HCTZ), 6.25 to 12.5 mg daily, and nifedipine, 30 to 60 mg daily, were added as needed. Ten patients completed 12 months of treatment. Trough blood pressure, heart rate, plasma creatinine, potassium, uric acid, cholesterol, renin activity (PRA), aldosterone, and norepinephrine were measured at baseline and after 1 and 12 months of treatment. Losartan lowered mean arterial pressure significantly from 119 +/- 2 mm Hg at baseline to 113 +/- 2 mm Hg (P < .05) after 1 month of treatment. Coadministration of HCTZ and nifedipine further decreased the mean arterial pressure to 103 +/- 2 mm Hg after 12 months of treatment. Plasma levels of creatinine, potassium, uric acid, cholesterol, and norepinephrine remained unchanged. PRA increased and plasma aldosterone decreased significantly (P < .05). The decrease in mean arterial pressure was related to baseline PRA (r = 0.53, P < .05). and to the change in PRA (r = 0.52, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The reliability of the mean normal prothrombin time of fresh plasmas and of the normal value from a lyophilized 'normal' plasma in prothrombin ratio determination.

The mean normal prothrombin time (MNPT) based on the fresh plasma of 20 healthy individuals is the recommended way to derive a normal value for the prothrombin ratio. This is generally believed to give a reasonable representation of the normal in the local population, but there may be difficulty in obtaining a good representative sample in some centres. The alternative of a uniform lyophilized 'normal' plasma has been suggested. The comparative value of a widely used commercial 'normal' plasma and the MNPT has been assessed in an international study at 37 centres. Two common thromboplastins were tested using the local coagulometer methods. The variability of the results and their relative performance in local thromboplastin calibration to derive the International Sensitivity Index (ISI) were assessed. The reliability of the two types of normal in local system ISI calibration with different lyophilized plasma calibrants has also been tested. When the lyophilized 'normal' was substituted for the MNPT in ISI determination no appreciable difference in the degree of correction for coagulometers effects on International Normalized Ratios was found.

Calibration↗

Increased expression of ICAM-1 during reoxygenation in brain endothelial cells.

BACKGROUND AND PURPOSE: Thrombolysis is a promising therapy for acute ischemic stroke. However, there is evidence that neutrophils may physically plug cerebral microvessels on reperfusion, preventing the full benefit of thrombolysis. We undertook this study to determine whether there was increased endothelial expression of the intercellular adhesion molecule-1 (ICAM-1) gene during hypoxia-reoxygenation. METHODS: We isolated and cultured human brain microvascular endothelial cells and subjected them to hypoxia (PO2 < 10 mm Hg) in an anaerobic chamber followed by variable periods of reoxygenation. RESULTS: Twenty-hour periods of hypoxia did not lead to endothelial cytotoxicity as measured by a chromium-release assay. By Northern blot analysis, ICAM-1 mRNA transcripts were dramatically increased at 4 hours of reoxygenation but fell toward baseline (normoxia) by 12 and 24 hours. Hypoxia alone did not lead to an increase in mRNA levels. Western blot analysis showed an increased expression of ICAM-1 at 4, 12, and 24 hours of reoxygenation. The 4-hour increase in mRNA levels was not attenuated by pretreatment with 100 mumol/L allopurinol but was reduced by 30% with the addition of 20 mmol/L N-acetyl-L-cysteine at the time of reoxygenation and completely prevented by pretreatment with N-acetyl-L-cysteine. CONCLUSIONS: Hypoxia-reoxygenation leads to an increase in ICAM mRNA levels that peaks at 4 hours in human brain microvascular endothelial cells. Pretreatment with N-acetyl-L-cysteine can completely block the increase in ICAM-1 mRNA levels.

Brain↗

Spatiotemporal dynamics of intracellular [Ca2+]i oscillations during the growth and meiotic maturation of mouse oocytes.

Calcium oscillations occur during meiotic maturation of mouse oocytes. They also trigger activation at fertilization. We have monitored [Ca2+]i in oocytes at different stages of growth and maturation to examine how the calcium release mechanisms alter during oogenesis. Spontaneous calcium oscillations occur every 2-3 minutes in the majority of fully grown (but immature) mouse oocytes released from antral follicles and resuming meiosis. The oscillations last for 2-4 hours after release from the follicle and take the form of global synchronous [Ca2+]i increases throughout the cell. Rapid image acquisition or cooling the bath temperature from 28 degrees C to 16 degrees C did not reveal any wave-like spatial heterogeneity in the [Ca2+]i signal. Calcium appears to reach highest levels in the germinal vesicle but this apparent difference of [Ca2+] in nucleus and cytoplasm is an artifact of dye loading. Smaller, growing immature oocytes are less competent: about 40% are able to resume meiosis and a similar proportion of these oocytes show spontaneous calcium oscillations. [Ca2+]i transients are not seen in oocytes that do not resume meiosis spontaneously in vitro. Nonetheless, these oocytes are capable of [Ca2+]i oscillations since they show them in response to the addition of carbachol or thimerosal. To examine how the properties of calcium release change during meiotic maturation, a calcium-releasing factor from sperm was microinjected into fully grown immature and mature oocytes. The sperm-factor-induced oscillations were about two-fold larger and longer in mature oocytes compared to immature oocytes. Calcium waves travelling at 40-60 microns/second were generated in mature oocytes, but not in immature oocytes. In some mature oocytes, successive calcium waves had different sites of origin. The modifications in the size and spatial organization of calcium transients during oocyte maturation may be a necessary prerequisite for normal fertilization.

Animals↗

Effect of cryopreservation on development and ultrastructure of preimplantation embryos from the dasyurid marsupial Sminthopsis crassicaudata.

The effect of different cryopreservation methods on the development and ultrastructure of preimplantation embryos of Sminthopsis crassicaudata, a small carnivorous marsupial and member of the family Dasyuridae, was investigated. Females were primed with 1 iu pregnant mares' serum gonadotrophin to induce oestrus and ovulation. Mating generally ensued and, approximately 6 days after priming, embryos were collected and cultured in 5% CO2 in air at 35 degrees C for 18-22 h in either Dulbecco's modified Eagles medium (DMEM) with high glucose or human tubal fluid medium (HTF), both supplemented with 10% fetal calf serum. Cleavage rates were higher in DMEM than in HTF. One slow and two ultrarapid freezing methods were used. Two out of 12 (17%) embryos cleaved in culture after freezing and thawing using the slow regimen, compared with six of 16 (38%) non-frozen controls. In addition, two of 11 (18%) embryos cleaved in culture following ultrarapid freezing and thawing by one of the two methods, compared to 31 of 41 (76%) non-frozen controls. Most of the embryos appeared morphologically normal under the light microscope after freezing and thawing by the slow regimen, but considerable variation in the degree of ultrastructural damage to the cellular organelles was evident with the transmission electron microscope. The rather low rate of cleavage after freezing and thawing was probably due, at least in part, to ultrastructural damage of the cells.

Animals↗

Efficient catheter-mediated gene transfer into the heart using replication-defective adenovirus.

The ability to express recombinant genes in the coronary vasculature and the myocardium holds promise for the treatment of a number of acquired and inherited cardiovascular diseases. Previous in vivo gene transfer approaches in the heart have been limited by relatively low efficiencies of gene transduction. In this report, we demonstrate that catheter-mediated infusion of replication-defective adenovirus into the coronary arterial circulation in vivo represents a novel and efficient method for the induction of recombinant gene expression in both the coronary arteries and the myocardium. A single intracoronary infusion of 2 x 10(9) - 1 x 10(10) p.f.u. of adenovirus resulted in high level recombinant gene expression in both the coronary arteries and surrounding myocardium of adult rabbits for at least 2 weeks. No inflammatory response or myocardial necrosis was observed following the adenovirus infusions. The polymerase chain reaction (PCR) was used to assess the tissue distribution of infection following intracoronary infusion of adenovirus. Adenovirus DNA was detected by PCR in the livers, kidneys, lungs, brains and testes of animals 5 days after virus infusion. Percutaneous transluminal gene transfer (PTGT) into the heart by intracoronary infusion of replication-defective adenovirus represents a relatively non-invasive and efficient method of inducing recombinant gene expression both in the coronary arterial wall and in the surrounding myocardium.

Adenoviridae↗

Both the basal and inducible transcription of the tyrosine hydroxylase gene are dependent upon a cAMP response element.

The cAMP response element (CRE) mediates cAMP responsiveness in many eukaryotic genes (Roesler, W. J., Vandenbark, G. R., and Hansen, R. W. (1988) J. Biol. Chem. 263, 9063-9066). The tyrosine hydroxylase gene (TH) contains a single copy of a consensus CRE at -45 to -38 base pair (bp) upstream of the transcription initiation site. Deletional and mutational analyses of the upstream 2400-base pair region of the rat TH gene using transient transfection assay demonstrated that the CRE was essential for both cAMP-mediated induction and basal transcription of the TH gene. Another domain between -365 and -151 bp, containing the AP1 site, contributed to transcription to a smaller degree. Thus, the CRE appears to play an important dual role as a basal promoter element and an inducible enhancer for TH transcription. Interactions between the DNA binding factors in nuclear extract and CRE-containing oligonucleotides were investigated by gel retardation and competition assays. Oligonucleotides corresponding to the CRE regions of the TH or somatostatin gene gave rise to a pair of distinct protein-DNA complexes with identical mobilities in the gel retardation assay, suggesting that similar nuclear factor(s) might bind to the CREs of the TH and somatostatin genes. This study emphasizes a fundamental role of the CRE in transcriptional activation of the TH gene in catecholaminergic cells.

Animals↗

An analysis of Bacillus thuringiensis delta-endotoxin action on insect-midgut-membrane permeability using a light-scattering assay.

Changes in the membrane permeability of Manduca sexta midgut brush-border-membrane vesicles (BBMV) after addition of Bacillus thuringiensis delta-endotoxins were studied using osmotic swelling experiments, volume changes being monitored as the change in 90 degrees light scattering. Typically, control BBMV exhibited limited permeability for sucrose and salts (KCl), while being permeable for urea and glucose. The action of delta-endotoxin was examined using proteolytically activated Cry-IA(c) and CryIB toxins. CryIA(c) produced a marked change in the solute permeability of M. sexta BBMV, significant effects being observed at 3.75 pmol/mg BBMV. The permeability change was relatively non-selective with cations, anions and neutral solutes all traversing the membrane to an increased extent in the presence of CryIA(c). In contrast, the CryIB toxin had no effect on BBMV permeability.

Animals↗

Antibody development against northern fowl mites (Acari: Macronyssidae) in chickens.

This study reports the development of an antibody against protein(s) from the tissue of the northern fowl mite, Ornithonyssus sylviarum (Canestrini & Fanzago). Northern fowl mite proteins were obtained by affinity chromatography and used for immunization. Western blot analysis identified proteins that were reactive with sera from birds immunized with the antigen; this indicated that serum antibodies against the northern fowl mite had been produced. Chickens that had been immunized or infested, or both, with the northern fowl mite produced sera that were reactive with a 100 kilodalton (kD) protein. The response was greater if the chicken had been immunized with the antigen and infested with the northern fowl mite. Experimentally immunized and infested chickens experienced limited decreases in the levels of northern fowl mite infestation. Survival of bloodfed mites after ingestion of the immune chicken blood was assessed in an in vitro feeding study using blood-filled parafilm sacs; minor differences in northern fowl mite feeding tendencies were noted. The chickens developed antibodies to the northern fowl mite proteins, but this immunity did not decrease the infestation level or in vitro feeding.

Animals↗

Transplantation of frozen-thawed mouse primordial follicles.

Primordial follicles were isolated from juvenile mouse ovaries and cryopreserved by slow freezing with dimethylsulphoxide as the cryoprotectant. After thawing, approximately 80% of the oocytes and 65% of the somatic cells excluded Trypan Blue dye, indicating that cell membranes were still intact. Frozen-thawed cells were suspended in plasma clots and transplanted to the ovarian bursas of host animals that had been sterilized by oophorectomy. The grafts of frozen-thawed cells reorganized into morphologically distinguishable ovaries which produced signs of oestrogenic activity. After natural mating, host females produced normal offspring that were demonstrated by genetic markers to be derived from the transplanted frozen-thawed primordial follicles.

Animals↗

The role of calcium in mammalian oocyte maturation and egg activation.

The maturation of the immature oocyte and the fertilization of a mature egg are two absolute prerequisites for mammalian embryo development. There is increasing evidence in mammals that both oocyte maturation and egg activation at fertilization are controlled by changes in intracellular free Ca2+ levels. The role of Ca2+ changes at fertilization is clear in that they are both required and sufficient for egg activation. However, it is not established how the sperm causes Ca2+ changes in eggs at fertilization, nor how different patterns of Ca2+ change affect embryo development. The role of Ca2+ in triggering oocyte maturation is less clear, although preventing intracellular Ca2+ changes can inhibit meiotic maturation at specific stages. Studies on how Ca2+ regulates meiosis and fertilization in mammals may provide new insights into the causes of failed fertilization in human IVF procedures.

Animals↗

Normal fertilization and development of frozen-thawed mouse oocytes: protective action of certain macromolecules.

Freezing and thawing of mouse oocytes causes changes in the zona pellucida that reduce fertilization. The fertilization and development of oocytes were studied after freezing and thawing in media containing 1.5 M dimethylsulfoxide (DMSO) and various macromolecular supplements: BSA (Fraction V and crystalline), fetal calf serum (FCS), and polyvinyl alcohol (PVA). In conditions under which the fertilization rate of oocytes frozen in medium containing BSA was reduced, oocytes frozen in medium containing FCS were fertilized at rates approaching those of nonfrozen controls. Significantly fewer oocytes were fertilized after freezing in the presence of PVA than oocytes frozen in medium containing BSA or FCS. Fertilization of oocytes frozen in the presence of PVA was significantly increased when serum was included in the medium during dilution of the cryoprotectant. The in vitro and in vivo development of embryos obtained from frozen-thawed oocytes was independent of the macromolecular supplement used in the freezing medium and was similar to that of nonfrozen control oocytes. The results show that given the appropriate conditions for freezing and thawing, cryopreserved mouse oocytes undergo fertilization and development at rates similar to those for nonfrozen controls.

Animals↗