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Biomedical subjects

K Jeffery

Publications and source records attributed to K Jeffery.

9 recordsLinked to original sources

A highly restricted T-cell receptor dominates the CD8+ T-cell response to parvovirus B19 infection in HLA-A*2402-positive individuals.

Six of seven HLA-A*2402-positive individuals with acute parvovirus B19 infections made vigorous CD8-positive cytotoxic T-cell (CTL) responses to the viral epitope FYTPLADQF. All responders showed highly focused T-cell receptor (TCR) usage, using almost exclusively BV5.1. The BV5.1 TCR dominated the acute response, was maintained over time, and was also used by a remotely infected individual. Nine CTL clones and two oligoclonal lines obtained from three unrelated individuals used BV5.1, BJ2.1, and a conserved TCR CDR3 of nine amino acids. This commonly recognized epitope is likely important in long-term protective immunity and should be included in vaccine design.

CD8-Positive T-Lymphocytes↗

A phase II study of caelyx, liposomal doxorubicin: lack of activity in patients with advanced gastric cancer.

PURPOSE: A phase II study was designed to assess the efficacy and safety of Caelyx (liposomal doxorubicin) in patients with advanced or metastatic gastric cancer. METHODS: A total of 25 patients with gastric adenocarcinoma were treated with Caelyx 45 mg/m2 every 28 days as first-line therapy for advanced disease. Patients were treated until tumour progression or unacceptable toxicity. RESULTS: One patient was withdrawn from the study after experiencing a severe infusion reaction. Of the 24 evaluable patients, 1 had a partial response, 7 had stable disease and the others progressed. Side effects, in particular palmar-plantar erythrodysaesthesia and haematological toxicity, were minor. CONCLUSIONS: We conclude that while this dose and schedule of Caelyx in this patient group is acceptable, further studies with this regimen cannot be recommended due to the lack of antitumour activity seen.

Adenocarcinoma↗

LTP-like synaptic efficacy changes following electroconvulsive stimulation.

Synaptic plasticity is thought to represent a mechanism for memory formation. Memory disturbances commonly follow electroconvulsive therapy (ECT) for depression. Accordingly, we examined the development and duration of the effects of electroconvulsive stimulation (ECS) on hippocampal synaptic plasticity in rats. Daily recording of field potentials during 10 spaced ECS revealed an increase in the dentate gyrus evoked response, reaching a maximum after the fifth seizure. In a second experiment, an identical ECS series substantially reduced the degree to which electrically induced synaptic changes (long-term potentiation--LTP) could be elicited under anaesthesia for up to 40 days. These findings suggest that ECS induces LTP-like long-lasting synaptic changes which may underlie the neuropsychological sequelae of ECT treatment in humans.

Animals↗

Changes in cell surface antigens during stem cell ontogeny.

A panel of monoclonal antibodies that bind to the murine pluripotential stem cell CFU-s was used to examine the antigenic profile of the stem cell during ontogeny. The results show that the stem cell surface changes dramatically during development. One group of three independently derived monoclonal antibodies binds to subpopulations (50%-70%) of stem cells at plateau values, and these populations increase marginally during development. A second group of four monoclonal antibodies, including anti-H-2Kk (11-4.1), define stem cell antigens that increase from low levels in the fetal liver to high levels in adult bone marrow. The presence of these two classes of antigens on adult splenic stem cells was in general similar to that observed on adult bone marrow. Antigens defined by the first group of monoclonal antibodies were present in similar amounts on CBA, C57B1/6, and Balb/c bone marrow stem cells, whereas antigens of the second group showed mouse strain variations. Quantitative absorption analysis was used to distinguish H-2Kk (11-4.1) from 9F6, which showed a similar developmental profile. Monoclonal antibodies recognizing subpopulations of stem cells were shown to be distinct by complementation studies and recognized antigens not present on brain tissue.

Animals↗

Response of the diaphragm muscle to electrical stimulation of the phrenic nerve. A histochemical and ultrastructural study.

The histological, histochemical, and ultrastructural features of canine diaphragms subjected to pacing by high-frequency electrical stimulation (27 to 33 Hz) of the phrenic nerve are compared with unstimulated diaphragms and with diaphragms subjected to pacing by low-frequency stimulation (11 to 13 Hz). The high-frequency group showed a reduced tidal volume (fatigue) after long-term stimulation, and myopathic changes which included enlarged internal and sarcolemmal nuclei, ring fibers, moth-eaten fibers with irregular histochemical staining, core/targetoid fibers, and smearing and aggregation of Z-band material with electron microscopy. The low-frequency group did not develop a significant degree of fatigue or pathological changes, and showed histochemical evidence of transformation to fast-twitch (type II) fibers. Possible pathogenic mechanisms and their similarity to those in certain human neuromuscular diseases are discussed. The application of the findings resulting from high- and low-frequency stimulation to long-term diaphragm pacing in humans with chronic ventilatory insufficiency is also discussed.

Animals↗

Recombination analysis of naturally diploid Candida albicans.

A multiply auxotrophic strain, hOG45, was derived from Candida albicans ATCC 10261. Prototrophic revertants of this multiple auxotroph were selected after mutagenesis. These prototrophic revertants were distinguishable from the original prototroph, ATCC 10261, because of their mitotic instability. They gave rise to auxotrophic derivatives which displayed one or more of the auxotrophic requirements characteristic of hOG45. Two of the auxotrophic requirements, those for adenine and methionine, frequently reappeared together in the auxotrophic derivatives of the prototrophic revertants. This apparent linkage of ade and met was confirmed by protoplast fusion analysis of the original auxotroph. These data indicate that C. albicans ATCC 10261 is diploid, the multiple auxotroph h0G45 is homozygous for recessive auxotrophic alleles, the prototrophic revertants are multiple heterozygotes, the auxotrophic derivatives are homozygotes produced by mitotic crossing-over, and the association between the ade and met alleles is due to linkage.

Adenine↗

Parasexual genetic analysis of Candida albicans by spheroplast fusion.

Doubly auxotrophic strains of Candida albicans were selected from mutagenized cultures. Spheroplasts prepared from the auxotrophic strains were fused with polyethylene glycol. Prototrophic derivatives formed by this fusion protocol from auxotrophic strains were selected by complementation on minimal medium. These prototrophs had a cell volume twice that of the original strain and were shown to be heterozygous at four loci. Prototrophs obtained by this procedure infrequently gave rise to auxotrophic recombinants whose cell volume remained twice that of the original strain. It is suggested that these auxotrophic recombinants arise from mitotic crossing-over. This paper is the first report of a parasexual cycle in C. albicans.

Candida albicans↗