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Biomedical subjects

J Wright

Publications and source records attributed to J Wright.

At least 433 records · Page 24Linked to original sources

Differentiation of human hematopoietic cells increases expression of a gene transferred by a retroviral vector.

To study expression of a retroviral vector in human hematopoietic lineages, two established human hematopoietic cell lines (HL60 and K562) and a human adherent stromal cell line (KM101) were infected with the vector pZIP-SV(X). Expression of the transferred neomycin resistance gene (neor) of pZIP-SV(X) was evaluated as the ability of the cells to form colonies (greater than 50 cells) in an agar assay in the presence of the neomycin analogue, G418. After infection, all three cell lines produced colonies resistant to G418. The level of neor mRNA in separate colonies was analyzed by Northern blot analysis. The neor gene transferred by the vector pZIP-SV(X) was expressed in both human hematopoietic and stromal cell lines. In addition, primary adherent human stromal cells infected with pZIP-SV(X) grew in the presence of G418. To determine if differentiation of hematopoietic cells affects expression of the retroviral vector, HL60 cells infected with pZIP-SV(X) were induced to differentiate, and the level of neor mRNA measured. The amount of neor mRNA increased when HL60 cells were induced to differentiate along the granulocytic pathway. Conversely, when HL60 cells were induced toward monocytoid differentiation (TPA), the level of neor mRNA did not significantly increase. We conclude that the neor gene transferred by a retroviral vector, pZIP-SV(X), is functionally expressed. In addition, expression of the transferred neor gene is regulated during myeloid differentiation of HL60 cells.

Cell Differentiation↗

Laboratory diagnosis and clinical significance of rubella in children with cancer.

Virus-specific antibody responses were studied in 12 children with cancer in whom rubella was diagnosed by seroconversion or a rising titre (greater than or equal to fourfold) of haemagglutination inhibiting (HI) antibody. Our results confirmed the difficulties of making a diagnosis of rubella infection in immunocompromised children using criteria for interpreting antibody assays established in immunocompetent patients. Specific IgM antibody persisted for more than 2 months in 7 of 10 children with probable primary rubella, 3 of whom had high concentrations of such antibody 6, 7 and 11 months after the rash. Radial haemolysis and specific IgG1 and IgG3 antibody responses were low in 4, 2, and 4 patients, respectively. One child apparently had a rubella reinfection and, in another, rubella antibody passively acquired from blood transfusions was probably responsible for the HI seroconversion. Nonetheless, the benign clinical course of rubella in immunocompromised children was confirmed.

Antibodies, Viral↗

A nuclear magnetic resonance (NMR) method for the determination of the cis/trans isomeric content of chlorprothixene.

Proton NMR spectroscopy was applied to the assignment of the isomeric identity of commercially available chlorprothixene. Nuclear Overhauser effect studies confirmed that the clinically useful isomer is the cis (Z) configuration. An NMR method for determining the isomeric content of chlorprothixene was developed based on integration of the ratio of areas of signal strength of the cis-N-methyl in comparison to the trans-N-methyl resonances.

Chlorprothixene↗

Safety evaluation of meropenem in animals: studies on the kidney.

The effect of meropenem on animal kidneys has been assessed in rats (5 of each sex/group), rabbits (3 of each sex/group) and monkeys (3 of each sex/group) in comparative iv studies with ceftazidime, cefotaxime, cephaloridine and imipenem (without cilastatin). Diarrhoea occurred in rabbits and monkeys dosed with imipenem or meropenem. Emesis occurred only after the administration of imipenem to monkeys. After 14 days administration to rats evidence of nephrotoxicity was seen only in males dosed with cephaloridine (850 mg/kg); no changes were seen with ceftazidime, cefotaxime or meropenem (all at 1000 mg/kg). Four days after a single dose to rabbits renal tubular necrosis was seen in all animals receiving imipenem (150 mg/kg) and cephaloridine (250 mg/kg). Minimal histopathological changes to the kidneys were seen with cefotaxime, ceftazidime and meropenem (all at 400 mg/kg). After seven days' administration to cynomolgus monkeys imipenem (180 mg/kg) caused moderate to severe tubular necrosis. No tubular damage was seen with meropenem at 180 mg/kg or with cefotaxime or ceftazidime (both at 500 mg/kg). At 500 mg/kg meropenem caused mild tubular regeneration and/or fat accumulation in 3/6 animals, with mild tubular necrosis in one of these. The data from these three species indicate that meropenem has a low nephrotoxic potential in these animal models.

Animals↗

Sunbed-induced pseudoporphyria.

The clinical details of four fair-skinned women with recurrent blistering and skin fragility are presented. All had considerable sun-exposure and had used sunbeds for years. Specific causes of bullous dermatoses including drug ingestion, porphyria, cutaneous amyloidosis and epidermolysis bullosa acquisita were excluded. Long-term recurrent exposure to high doses of sunbed radiation in chronically sun-damaged skin appears to be a further cause of pseudoporphyria.

Adult↗

Ductus arteriosus: involvement of a sarcolemmal cytochrome P-450 in O2 constriction?

Our previous studies implicate a cytochrome P-450-based mechanism in the constrictor response of the ductus arteriosus to oxygen. The present experiments were conducted on saponin-skinned strips of ductal muscle from mature fetal lambs to determine the location, sarcolemmal versus intracellular, of this cytochrome and to obtain a better insight into the sequence of events underlying the action of oxygen. Skinned preparations contracted to free Ca2+ over the range between 0.1 and 5-10 microM (pCa 7 to 5). In contrast, oxygen (PO2, 608-690 Torr; 1 Torr = 133.3 Pa) had no significant effect, both in the absence and presence of 10 microM calcium. Carbon monoxide, tested as pure CO or a CO-O2 mixture (ratio 0.28), did not relax preparations maximally contracted with calcium. These findings indicate that oxygen exerts its effect on the plasma membrane of ductus muscle cells and that a membrane-bound cytochrome P-450 mechanism likely functions as the signal transducer for oxygen in the formation of a constrictor agent.

Animals↗

Systemic senile amyloidosis. Identification of a new prealbumin (transthyretin) variant in cardiac tissue: immunologic and biochemical similarity to one form of familial amyloidotic polyneuropathy.

Isolated amyloid fibrils from three cases of systemic senile amyloidosis (SSA) contained subunit proteins with molecular masses of 14 (10-20%), 10-12 (60-80%), and 5-6 kD (5-10%) when fractionated under reducing and dissociating conditions. This grouping was identical to that seen in SKO, a case of familial amyloidotic polyneuropathy (FAP) studied earlier. Amino acid sequencing confirmed that SSA subunit proteins were in fact prealbumin (transthyretin). Complete sequence analysis of one SSA preparation revealed the presence of a new variant Pa (TTr) molecule with a single amino acid substitution of isoleucine for valine at position 122. Further studies used an antiserum specific for SKO IV, a subunit protein of SKO previously shown to correspond to carboxy-terminal 78 residues (positions 49-127) of (TTr). Anti-SKO IV reacted with SSA in tissue at equivalent dilutions to anti-Pa (TTr) and with the 10-12-kD fraction of SSA on Western blots; reactivity was blocked by SKO IV, but not by Pa (TTr). SSA is a form of systemic amyloidosis caused by tissue deposition of Pa (TTr) and its fragments, with shared conformational or subunit antigenicity to at least one form of FAP. Identification of a new variant Pa (TTr) molecule in one case suggests further that SSA may be a genetically determined disease expressed late in life.

Amino Acid Sequence↗

Functional and morphologic comparison of silica- and elastase-induced airflow obstruction.

We have previously shown that intratracheally instilled silica (quartz) produces both morphologic evidence of emphysema and small-airway changes, and functional evidence of airflow obstruction. To further define the nature of the airflow-associated lesions induced by silica, we compared silica-exposed rats to rats given intratracheal elastase, a standard model of emphysema. Both silica and elastase produced increases in RV and FRC along with upward shifts in the pressure-volume curves. Flows were decreased in both groups, but the changes were more severe in the silica-treated animals. Morphologically, the two treatments produced about the same degree of airspace enlargement, present in both alveoli and alveolar ducts, as well as decreased alveolar and alveolar duct surface area/unit lung volume. Elastic fiber length per unit volume was also decreased in both groups. However, small-airway walls were markedly thickened in the silica-treated compared to the elastase-treated group. We conclude that, in the parenchyma, both these agents produce morphologically similar airspace dilatation, and both induce destruction of elastic fibers. These lesions appear to correlate with abnormalities in the pressure-volume curve. Flow reductions seem to be primarily correlated with changes in small-airway wall structure.

Animals↗

What have 30 years of medical progress done for cerebral palsy?

This article salutes Sherman Coleman for his work for children with cerebral palsy and reviews the accomplishments over the past 30 years. During this time, much has changed. Yet, we are only a little closer to ridding these children of the grasp that spasticity has on their limbs.

Cerebral Palsy↗

[A space-occupying hemorrhage following spinal anesthesia in the presence of an undiagnosed small spinal tumor (ependymoma)].

Space-occupying subarachnoid bleeding after atraumatic puncture of the spinal canal for spinal anesthesia in a patient with no coagulation disorders or anticoagulant therapy is described. The hematoma was caused by puncturing a previously undiagnosed small spinal ependymoma. A thorough and specific preoperative evaluation is of importance to minimize the risks associated with spinal anesthesia.

Anesthesia, Spinal↗

Scavengers of active oxygen species prevent cigarette smoke-induced asbestos fiber penetration in rat tracheal explants.

It was previously shown that rat tracheal explants first exposed to cigarette smoke and then to amosite asbestos take up more asbestos fibers than explants exposed to air and asbestos. To examine the mechanism of this process, the same experimental design was followed but test groups were added in which the asbestos was mixed with catalase or superoxide dismutase, scavengers of active oxygen species, or deferoxamine, an iron chelator that prevents formation of hydroxyl radical. All three agents protected against the cigarette smoke effect. Heat inactivated catalase or superoxide dismutase was not protective. These observations indicate that active oxygen species, probably derived from the cigarette smoke, play a role in smoke-mediated fiber transport into tracheobronchial epithelia.

Animals↗