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Biomedical subjects

M B Llewelyn

Publications and source records attributed to M B Llewelyn.

14 recordsLinked to original sources
PubMed1997

Consequences of live poliovirus vaccine administration in chronic fatigue syndrome.

The effect of live oral polio virus vaccination on chronic fatigue syndrome (CFS) patients was examined in a double-blind study. CFS patients were allocated randomly to placebo (N = 7) or vaccine (N = 7) conditions. All controls subjects received the vaccine (9). Vaccine administration was not associated with clinical exacerbation of CFS. However, objective responses to the vaccine revealed differences between patients and controls: increased poliovirus isolation, earlier peak proliferative responses, lower T-cell subsets on certain days post vaccination and a trend for reduced gamma-interferon in the CFS-vaccine group. Polio vaccination was not found to be clinically contraindicated in CFS patients, however, there was evidence of altered immune reactivity and virus clearance.

Adult↗
PubMed1996

A malignant astrocytoma in a patient with AIDS: a possible association between astrocytomas and HIV infection.

We describe a malignant astrocytoma in a patient with AIDS confirmed at autopsy. The object of this report is to draw attention to a further example of an unusual tumour associated with HIV infection. This is the tenth case in the world literature and it is possible that this tumour is represented with a higher than expected frequency in this group of the population. This case and others add malignant astrocytoma to the differential diagnosis of an intracranial space occupying lesion in an AIDS patient.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Cutaneous infection with Tunga penetrans.

A 23-year-old man presented with a small black lesion at the distal margin of the right great toenail. He had returned from the Ivory Coast 1 month previously, having spent 6 weeks there. Histopathological examination of material extruded from the lesion showed a variety of arthropod internal organs, allowing a definitive diagnosis of infection with the ectoparasitic flea Tunga penetrans. Curettage of the lesion revealed a gravid adult female flea.

Adult↗
PubMed1992

Principles of antibody therapy.

The success of monoclonal antibodies in clinical practice is dependent on good design. Finding a suitable target is the most important part as other properties of the antibody can be altered by genetic engineering. Antibodies that target lymphocyte antigens offer less toxic immunosuppressive treatment than currently available drugs and the first monoclonal antibody approved for human use is an immunosuppressive agent for treating rejection of renal transplants. Human trails of monoclonal antibodies to treat septic shock have been done and antibodies are also being developed to target common pathogens such as herpes simplex virus. Although monoclonal antibodies against cancer have been much heralded, their success has been limited by the poor access to the inside of tumours. Treatment of blood cancers has been more successful and a human antibody against B cell malignancies is being clinically tested. As knowledge about natural immune responses and antibody engineering increases many more monoclonals are likely to feature in clinical practice.

Antibodies, Monoclonal↗
PubMed1992

Adapting antibodies for clinical use.

Techniques for antibody engineering are now overcoming the problems that have prevented monoclonal antibodies being used routinely in clinical practice. With chemical and genetic manipulation antibodies can be linked to bacterial toxins, enzymes, radionuclides, or cytotoxic drugs, allowing targeting of treatment. Antigen binding sites from antibodies raised in mice can be jointed with human IgG to reduce immunogenicity. In vitro gene amplification and genetic engineering of bacteriophage have produced large antibody gene libraries and facilitated large scale production of human monoclonal antibodies with high specificity. The trickle of monoclonal antibodies into clinical practice may soon become a flood.

Antibodies, Monoclonal↗
PubMed1992

Discovery of antibodies.

Passive immunisation has been used in clinical practice since the end of last century, mainly for prophylaxis. Success of early treatments was marred by anaphylactic reactions and serum sickness because antibodies or antitoxins were not raised in humans. Recombination of gene segments during antibody synthesis means that specific antibodies for numerous antigens can be produced from a limited gene pool. Killer lymphocytes, phagocytes, and complement then bind to the constant region of the antibody facilitating elimination of the pathogen. Development of a method of obtaining large quantities of antibodies against a specific antigen (monoclonal antibodies) offers the possibility of initiating host defence mechanisms against any unwanted antigen, though some problems still remain in preventing the body from attacking the monoclonal antibody.

Antibodies↗
PubMed1992

The repertoire of human germline VH sequences reveals about fifty groups of VH segments with different hypervariable loops.

We have used the polymerase chain reaction and VH family-based primers to clone and sequence 74 human germline VH segments from a single individual and built a directory to include all known germline sequences. The directory contains 122 VH segments with different nucleotide sequences, 83 of which have open reading frames. The directory indicates that the structural diversity of the germline repertoire for antigen binding is fixed by about 50 groups of VH segments: each group encodes identical hypervariable loops. The directory should help in mapping the VH locus, in estimating somatic mutation and VH segment usage and in designing and constructing synthetic antibody libraries.

Amino Acid Sequence↗
PubMed1992

Structural repertoire of the human VH segments.

The VH gene segments produce the part of the VH domains of antibodies that contains the first two hypervariable regions. The sequences of 83 human VH segments with open reading frames, from several individuals, are currently known. It has been shown that these sequences are likely to form a high proportion of the total human repertoire and that an individual's gene repertoire produces about 50 VH segments with different protein sequences. In this paper we present a structural analysis of the amino acid sequences produced by the 83 segments. Particular residue patterns in the sequences of V domains imply particular main-chain conformations, canonical structures, for the hypervariable regions. We show that, in almost all cases, the residue patterns in the VH segments imply that the first hypervariable regions have one of three different canonical structures and that the second hypervariable regions have one of five different canonical structures. The different observed combinations of the canonical structures in the first and second regions means that almost all sequences have one of seven main-chain folds. We describe, in outline, structures of the antigen binding site loops produced by nearly all the VH segments. The exact specificity of the loops is produced by (1) sequence differences in their surface residues, particularly at sites near the centre of the combining site, and (2) sequence differences in the hypervariable and framework regions that modulate the relative positions of the loops.

Amino Acid Sequence↗
PubMed1986

Brainstem mechanisms of antinociception. Effects of electrical stimulation and injection of morphine into the nucleus raphe magnus.

The microinjection of morphine into the nucleus raphe magnus (NRM) increased the tail-flick latency of rats but also increased the size of noxiously-evoked responses of dorsal horn neurones. Electrical stimulation of the raphe magnus reduced the response size of the same neurons to noxious stimulation. To control for the possibility that morphine had a membrane stabilising action upon cells in the raphe magnus, tetracaine was injected into the raphe magnus and found to reduce the size of noxiously-evoked responses of dorsal horn cells. Bilateral lesions of the dorsolateral funiculus reduced the effect on tail-flick latency of morphine injected into the raphe magnus, indicating that morphine was causing antinociception by an effect on descending systems. This effect of morphine was fundamentally different however from the effects of electrical stimulation. Antinociception may result from different mechanisms within the raphe magnus nucleus, affected by morphine and electrical stimulation.

Analgesia↗
PubMed1984

The effect of modification of 5-hydroxytryptamine function in nucleus raphe magnus on nociceptive threshold.

Thresholds to noxious heat stimulation were increased following microinjection of zimelidine, an inhibitor of 5-hydroxytryptamine (5-HT) re-uptake, into the nucleus raphe magnus (NRM) of rats. Pretreatment with intraperitoneally given cinanserin reduced this effect but pretreatment with intraperitoneally given phenoxybenzamine did not. Fenfluramine, which causes the release of 5-HT from synaptic terminals also elevated nociceptive thresholds following microinjection into NRM. Subanalgesic doses of morphine or zimelidine elevated nociceptive thresholds when microinjected together into NRM. The elevation of nociceptive threshold produced by microinjection of morphine into NRM was reduced by simultaneous microinjection of cinanserin into NRM. Cinanserin alone had no effect when microinjected into NRM. These findings suggest that inhibition of the re-uptake of 5-HT in NRM can elevate nociceptive thresholds and that there may be an interaction between the effects of morphine and 5-HT in NRM.

Animals↗
PubMedDate not supplied

Assessing the fatigued patient.

Fatigue is a very common symptom in the general population. Fatigue most commonly results from social circumstances or psychological difficulties. This article discusses how to approach the fatigued patient and what investigations are necessary.

Depressive Disorder↗