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Biomedical subjects

M Roberts

Publications and source records attributed to M Roberts.

At least 127 records · Page 7Linked to original sources
PubMed1995

Mucosal and systemic immunogenicity of a recombinant, non-ADP-ribosylating pertussis toxin: effects of formaldehyde treatment.

The effect of formaldehyde treatment on the mucosal and systemic immunogenicity of the genetically detoxified pertussis toxin (PT-9K/129G) was investigated. Groups of BALB/c were immunized intranasally (i.n.) or subcutaneously (s.c.) with untreated, lightly formaldehyde treated (LFT) or heavily formaldehyde treated (HFT) recombinant pertussis toxin (PT) mutant, PT-9K/129G. Intranasal immunization with native PT-9K/ 129G induced significant levels of anti-toxin antibodies in serum and IgA anti-toxin responses in nasal and lung lavages of these mice. Similar local and systemic responses were observed following intransal immunization with LFT toxin. However, i.n. immunization with HFT toxin failed to induce a local IgA response and elicited a much diminished anti-toxin response in the serum. In contrast, the total antibody response following s.c. immunization was not significantly affected. In addition, i.n. immunization with native PT-9K/129G induced low but detectable levels of toxin neutralizing antibodies in the serum. These results show that native PT-9K/129G protein acts as a mucosal immunogen in mice and that this activity is greatly diminished by HFT of the protein.

Administration, Intranasal↗
PubMed1995

Autoantibodies, neurotoxins and the nervous system.

Myasthenia gravis, the Lambert-Eaton myasthenic syndrome, and acquired neuromyotonia are three disorders of the neuromuscular junction or motor nerve that are caused by autoantibodies to ion channel proteins: acetylcholine receptors, voltage-gated calcium channels and voltage-gated potassium channels, respectively. The antibody titres can be measured using the relevant 125I-neurotoxins to label the extracted channels. Other disorders of the peripheral motor nerve are associated with antibodies to gangliosides. Sera with raised levels of anti-ganglioside antibodies have direct effects on the function of the distal motor nerve and motor nerve terminal. These conditions can be improved by therapies designed to reduce circulating antibodies. Antibodies that bind to neuronal surface antigens are proving to be of great clinical importance and interest in neurological disorders.

Autoantibodies↗
PubMed1995

The development of oral vaccines against parasitic diseases utilizing live attenuated Salmonella.

Genetically defined, live attenuated Salmonella vaccines are proving useful both as oral vaccines against salmonellosis and for the development of multivalent vaccines based on the expression of heterologous antigens in such strains. Several candidate attenuated S. typhi strains are at present being evaluated as new single dose oral typhoid vaccines in human volunteers. The emergence of such a vaccine will facilitate the development of multivalent vaccines for humans. Many antigens from different infectious organisms have been expressed in attenuated Salmonella. A focus of this work has been on developing vaccines against parasitic diseases. This review will summarize the efforts that have been made in this area.

Administration, Oral↗
PubMed1995

The nutritional status and clinical course of acute admissions to a geriatric unit.

Undernutrition of long-stay hospital patients and those in surgical units is well documented. This study was designed to determine the extent of the problem in elderly people admitted to hospital with acute medical problems and to assess the relationship between nutritional status and course of hospital stay. Sixty-nine patients underwent a nutritional assessment on admission and at intervals throughout their hospital stay and episodes of sepsis were documented. Severely malnourished patients were identified using body mass index, BMI (22%) and corrected arm muscle area, CAMA (26%). Episodes of sepsis occurred significantly more often in the severely undernourished group (p < 0.04). The median length of stay of the group was 16 days (range 2-113): during this time there was no significant change in markers of nutritional status apart from actual muscle circumference (AMC), which showed a reduction in measurement between admission and discharge which was statistically significant (p < 0.0003). This study indicated that severe malnutrition is common in elderly medical admissions, and that it is associated with an increased risk of sepsis. Additional nutritional depletion may occur during hospital stay, and is not easily recognized unless anthropometry is undertaken.

Aged↗
PubMed1995

Iron supplying systems of Salmonella in diagnostics, epidemiology and infection.

Well-known and newly characterised mechanisms, both endogenous and exogenous, for the uptake of iron by Salmonella are outlined, and their possible roles at various stages in infection are discussed. The contributions of a detailed understanding of iron supplying systems to techniques for diagnosis, epidemiology and disease management are described.

Bacterial Outer Membrane Proteins↗
PubMed1995

Reversible and selective inhibitors of monoamine oxidase A in mental and other disorders.

The clinically tested reversible inhibitors of monoamine oxidase A (RIMAs) include brofaromine, moclobemide and toloxatone. Moclobemide has shown unequivocal antidepressant activity against serious depressive illness in 4 placebo-controlled double-blind trials. It has been compared with amitriptyline, imipramine, clomipramine, desipramine, maprotiline, fluoxetine, fluvoxamine, tranylcypromine, toloxatone, mianserin and amineptine in the treatment of depressive disorders. Meta-analysis showed convincing evidence of moclobemide efficacy, comparable with the most potent antidepressants available. The efficacy of moclobemide has been demonstrated in psychotic and non-psychotic depression, in depression with and without melancholia, in endogenous depression (both unipolar and bipolar), in retarded depression and in agitated depression. The efficacy of moclobemide, allied to the unusually benign side effect profile, has led to exploration of its use in other disorders. Two small studies have given encouraging results in the treatment of attention-deficit hyperactivity disorder. Large placebo-controlled studies have shown the activity of moclobemide in the depression that accompanies dementia (such as senile dementia of Alzheimer type). The results also suggested that, in this patient population, cognitive ability improved in parallel. Social phobia has also been shown to improve on treatment with either moclobemide or brofaromine. Clinical trials are in progress on the effect of moclobemide in chronic fatigue syndrome. Moreover, there are encouraging results with the use of brofaromine and moclobemide in panic disorder. Other disorders in which treatment with RIMA is of interest include agoraphobia, bulimia, borderline personality disorder, post-traumatic stress disorder, compulsive hair pulling (trichotillomania), dysmorphophobia, kleptomania as well as various anxiety syndromes.

Alzheimer Disease↗
PubMed1995

A mutant pertussis toxin molecule that lacks ADP-ribosyltransferase activity, PT-9K/129G, is an effective mucosal adjuvant for intranasally delivered proteins.

We examined the capacity of a genetically detoxified derivative of pertussis toxin (PTX), PT-9K/129G, to act as a mucosal adjuvant for an intranasally (i.n.) administered tetanus vaccine. Groups of mice were immunized i.n. with the nontoxic C-terminal 50-kDa portion of tetanus toxin (fragment C [Frg C]) either alone or mixed with PT-9K/129G, PTX, or cholera toxin (CT) or were immunized subcutaneously (s.c.) with an equivalent amount of Frg C adsorbed to alhydrogel. In response to a single immunization, mice receiving Frg C plus PT-9K/129G or CT i.n. and parenterally immunized mice developed high-titer (> 20,000) anti-Frg C antibodies, whereas mice immunized i.n. with Frg C plus PTX or with Frg C alone seroconverted only after being boosted. The serum anti-Frg C response was dominated by immunoglobulin G1 (IgG1) in mice immunized with Frg C plus PT-9K/129G, with Frg C plus PTX, or s.c. In contrast, IgG1, IgG2a, and IgG2b contributed almost equally to the Frg C response when CT was the adjuvant. Anti-Frg C IgE was detected only in the sera of mice immunized i.n. with Frg C plus PTX and immunized s.c. with Frg C plus alhydrogel. High levels of IgA antibodies were present in nasal lavage fluid from mice immunized i.n. with Frg C plus PT-9K/129G, PTX, or CT but not in that from mice given Frg C alone i.n. or parenterally. The mucosal adjuvanticity of PT-9K/129G was manifested in inbred as well as outbred mice. A single i.n. dose of Frg C plus either PT-9K/129G or PTX (with high specific activity) was sufficient to protect all immunized mice from tetanus toxin challenge, in contrast to the case for mice that received Frg C alone i.n. We conclude that the pertussis toxin analog PT-9K/129G, which is devoid of ADP-ribosyltransferase activity, is a potent mucosal adjuvant for vaccines delivered via the respiratory tract.

Adjuvants, Immunologic↗
PubMed1995

Allergic bronchopulmonary mycosis caused by Fusarium vasinfectum.

We present a case of allergic bronchopulmonary fusariosis (ABPF). This is the first case of allergic bronchopulmonary mycosis (ABPM) caused by Fusarium vasinfectum reported in the medical literature. The patient presented with a history and radiographic picture highly suggestive of allergic bronchopulmonary aspergillosis (ABPA), yet with negative ABPA serology results. The demonstration of a positive skin test and precipitins against F. vasinfectum, elevated serum IgG and IgE antibodies against F. vasinfectum, and a decline in total serum IgE with treatment clearly establish the diagnosis of ABPF. The diagnosis of ABPM caused by organisms other than Aspergillus represents an important consideration in patients who appear clinically to have ABPA but whose serology results do not confirm this diagnosis. As in ABPA, early diagnosis and appropriate therapy may be necessary in order to prevent progressive lung disease.

Aspergillosis, Allergic Bronchopulmonary↗
PubMed1995

Disordered water homeostasis in schizophrenia and cerebral ventricular size.

BACKGROUND: A possible association between disordered water homeostasis and cerebral ventricular size in patients with schizophrenia was investigated. METHOD: In a cross-sectional study of hospitalised patients, cerebral ventricular size was measured in 16 schizophrenic patients with disordered water homeostasis and 16 matched schizophrenic controls by magnetic resonance imaging. RESULTS: Ventricle to brain ratio, third ventricular index, bicaudate index and bifrontal index tended to be greater in those with schizophrenia with disordered water homeostasis, although differences were significant only for the bifrontal index (P < 0.05). Strong negative correlations were found between ventricular size and performance on neuropsychological testing in the disordered water homeostasis group. CONCLUSION: These results provide evidence for an association between structural brain abnormality and disordered water homeostasis in a subset of schizophrenic patients.

Cerebral Ventricles↗
PubMed1995

Porcelain onlays.

For years porcelain-fused-to-metal crowns have been the only restoration for posterior teeth in which strength and esthetics were important. Predictable results can now be achieved with a much more conservative approach--the bonded porcelain onlay. This article reviews the preparation designs as well as several types of materials currently available for the cosmetic onlay. An application using porcelain onlays to restore vertical dimension is explored. With this technique, moreover, the porcelain onlay is combined with porcelain veneer to achieve a functional and esthetic restoration.

Dental Cavity Preparation↗