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Biomedical subjects

E Mulvihill

Publications and source records attributed to E Mulvihill.

14 recordsLinked to original sources
PubMed1992

L-2-amino-4-phosphonobutyrate (L-AP4) is an agonist at the type IV metabotropic glutamate receptor which is negatively coupled to adenylate cyclase.

Glutamate and L-AP4 inhibited forskolin-stimulated cyclic AMP (cAMP) production in baby hamster kidney (BHK) cells transfected with the type IV metabotropic receptor (mGluR4). In situ hybridization revealed a high level of mRNA for the mGluR4 in the entorhinal cortex, but not in the dentate gyrus. These data demonstrate that mGluR4 receptors are negatively coupled to the cAMP cascade, and suggest that the mGluR4 receptor may be the previously described presynaptic L-AP4 receptor.

Adenylyl Cyclases↗
PubMed1992

A mammalian homologue of a transcript from the Drosophila pecanex locus.

The Drosophila pecanex locus contains a maternal-effect neurogenic gene. A homologue of this gene has not yet been described in mammals or other organisms. We report here a partial complementary DNA clone from rat brain mRNA that encodes sequences which are very similar (83% over 189 amino acids) to a portion of sequence encoded by a transcript from the Drosophila pecanex locus [LaBonne, S.G., Sunitha, I and Mahowald, A.P. (1989) Dev. Biology 136: 1-161].

Amino Acid Sequence↗
PubMed1991

Expression of recombinant human plasminogen in mammalian cells is augmented by suppression of plasmin activity.

We present evidence that over-expression of human plasminogen, the precursor to the serine protease plasmin, can be cytotoxic to mammalian cells. When an expression vector containing plasminogen cDNA is transfected into baby hamster kidney cells, the number of drug-resistant colonies as well as the levels of plasminogen secreted by those colonies is lower than observed in similar transfections of other protease precursor genes. The recombinant plasminogen accumulates intracellularly as degraded NH2-terminal fragments. In contrast, a mutant of plasminogen that produces inactive plasmin (active site Ser740 changed to Ala) is synthesized by these cells as a full-length plasminogen molecule, and the colony numbers and expression levels are normal. Thus, the generation of plasmin activity is responsible for the cytotoxic phenomena and the degradation associated with plasminogen expression. In addition, experiments using a plasminogen mutant that cannot be activated to plasmin (activation cleavage site Arg560 to Gly) or using coexpression of antisense urokinase RNA indicate that an endogenous plasminogen activator is responsible for converting newly synthesized plasminogen to plasmin. Finally, coexpression of plasminogen with alpha 2-plasmin inhibitor, a serpin which is the physiologic inhibitor of plasmin, prevents the toxic effects of intracellular plasmin activity and allows the synthesis and secretion of native human plasminogen.

Animals↗
PubMed1991

Prospective hospital study of community acquired lower respiratory tract infection in the elderly.

A prospective study of community acquired lower respiratory tract infection in the elderly was carried out over a 15-month period. During this time 127 consecutive admissions to two acute geriatric medical wards were studied. An aetiology was established in 77 (61%) of cases. Streptococcus pneumoniae was identified in 37% of patients. Haemophilus influenzae in 18% and Branhamella catarrhalis in 10%. Infection with Mycoplasma pneumoniae was found in only one episode and no cases of Legionella pneumophilia were diagnosed. A significant number of patients had multiple bacterial pathogens isolated: 18% of all bacterial pathogens isolated were ampicillin resistant. Fourteen patients died (11%). Lower respiratory tract infection is a frequent cause of hospital admission for those aged over 65 and is often regarded as a preterminal event. Adequately treated however, mortality is no higher than in the general population. Knowledge of the likely pathogens allows early and appropriate antibiotic therapy for these patients whether at home or on admission to hospital.

Aged↗
PubMed1990

Fibrin affinity and clearance of t-PA deletion and substitution analogues.

To investigate structure-function relationships in tissue-type plasminogen activator (t-PA) we deleted the following domains in the heavy chain: a) The epidermal growth factor domain (t-PA del. G), b) the finger domain, and the epidermal growth factor domain (t-PA del. FG), and c) the finger, the epidermal growth factor and Kringle 1 (t-PA del. FGK1). To study specifically the function of the growth factor domain we made two substitutions of d) 8 amino acids (consensus sequence) in the growth factor domain (t-PA G-CS) and e) the whole domain with factor IX growth factor domain (t-PA G-IX). Finally, f) an analogue with substitution in the finger domain (fibronectin consensus sequence) was constructed (t-PA F-CS). A reduced fibrin binding of all the analogues was found. The fibrin stimulated activity of all analogues was also reduced and correlated to the fibrin binding. In contrast, the activity of the analogues in the clot lysis assay and the plate assay were only slightly reduced as compared to authentic t-PA. This suggested that at high fibrin concentrations the decreased fibrin affinity was less critical for obtaining a high fibrinolytic activity. All analogues had a prolonged half-life in vivo as compared to authentic t-PA. The assumption of clearance mechanism involving mainly the growth factor region (or Kringle 1) was not challenged by the observation of a prolonged half-life for the substitution analogue t-PA F-CS.2+off

Amino Acid Sequence↗
PubMed1990

Haemolytic uraemic syndrome with shigella.

A 49-year-old male developed bloody diarrhoea whilst on a visit to India. Sigmoidoscopy and rectal biopsy showed acute colitis. Shigella dysentery type I was isolated from stool culture. Cytotoxin production by the organism was demonstrated. The patient developed acute renal failure, thrombocytopaenia and microangiopathic haemolytic anaemia. He required mechanical ventilation, haemodialysis, blood transfusion and antibiotic therapy and achieved a complete recovery. This is an unusual case of haemolytic uraemic syndrome complicating shigellosis in an adult.

Cefuroxime↗
PubMed1990

Lung pathology in HIV positive patients.

We describe the results of 43 bronchoscopic examinations carried out on 35 patients who were HIV positive. Of these, 13 were intravenous drug abusers, 13 were homosexual or bisexual, six were haemophiliacs, two were homosexual intravenous drug abusers and one was a heterosexual contact of a drug abuser. All underwent investigation because of respiratory symptoms. Aetiological diagnosis could not be made from physical examination, x-ray or routine laboratory tests but, was usually made using bronchoscopy and its associated investigations. Using these techniques, Pneumocystis carinii pneumonia was the commonest diagnosis (19 cases) followed by bacterial infection. Mycobacterial infection accounted for two cases and non-specific interstitial pneumonitis accounted for three. Kaposi's sarcoma was found in one instance and eight investigations were non-diagnostic.

Adult↗
PubMed1989

Effect of age on adherence of Branhamella catarrhalis to buccal epithelial cells.

The role of adherence in the pathogenicity of Branhamella catarrhalis in lower respiratory tract infection in the elderly was investigated. Differential adherence of this organism to buccal epithelial cells of elderly inpatients, outpatients, and young controls was measured. The mean number of bacteria adherent per cell was 36.9 +/- 11.2, 40.2 +/- 6.1 and 16.5 +/- 12.8 for inpatient and outpatient elderly and young controls respectively (significantly different p less than 0.01, Student's t test). This significantly higher level of adherence in the elderly subjects suggests that increased adherence may contribute to the incidence of respiratory tract infection due to B. catarrhalis seen in this group.

Adult↗
PubMed1989

Listeriosis: a community problem?

Three epidemiologically distinct cases of listeriosis, one perinatal and two adult, presented in hospital over a three day period. Clinical signs were non-specific with pyrexia and respiratory distress. Diagnosis in all three was made by blood cultures. Such cases reflect the general increase in reporting of listeriosis and suggest that the condition is increasing in incidence in the community, most likely due to food contamination. Raw vegetables, milk, soft cheeses, pre-cooked and inadequately cooked meats have all been implicated. Regular public health inspection of foods and food storage facilities with increased public awareness of the hazards of inadequate cooking and storage of food are the most effective means of preventing listeriosis and its potentially disastrous consequences especially for pregnant women and immunosuppressed patients.

Adult↗
PubMed1988

The expanded spectrum of toxocaral disease.

Among 137 members of 30 families, 6% (and 8% of those aged under 15 years) were seropositive for toxocara antibodies. In these seropositive subjects and in 84 patients known to have raised toxocara titres the commonest clinical features were abdominal pain, hepatomegaly, anorexia, nausea, vomiting, lethargy, sleep and behaviour disturbances, pneumonia, cough, wheeze, pharyngitis, cervical adenitis, headache, limb pains, and fever. 61% of patients with raised toxocara titres had recurrent abdominal pain. Eosinophilia was in many cases associated with a raised toxocara titre, but 27% of patients with high titres had normal eosinophil counts. Toxocariasis is common, especially in children, and is associated with clinical features that are generally regarded as non-specific but together form a recognisable symptom complex. Toxocariasis should be considered in the differential diagnosis of such symptoms and especially in recurrent abdominal pain, which might otherwise be labelled as idiopathic. The absence of eosinophilia does not exclude toxocariasis.

Adolescent↗
PubMed1988

The effect of polymerised fibrin on the catalytic activities of one-chain tissue-type plasminogen activator as revealed by an analogue resistant to plasmin cleavage.

A one-chain recombinant tissue-type plasminogen activator (EC 2.4.31.-) (tPA) analogue was constructed in which Arg-275 of the activation site was changed to Gly by site-directed mutagenesis. This analogue, tPA-Gly275, was very resistant to plasmin (EC 2.4.21.5) cleavage. It has been used to gain information about the activity of the uncleaved one-chain tPA form, also when plasmin is generated as a result of a plasminogen activation reaction. The amidolytic activity of tPA-Gly275 with less than Glu-Gly-Arg-pNA was investigated and compared to that of one-chain and two-chain wild-type recombinant tPA. A small but significant intrinsic amidolytic activity was observed with the analogue as well as the wild-type one-chain tPA form. However, it was much lower than that of two-chain tPA. Polymerised fibrin enhanced the amidolytic activity of both one-chain tPA forms but not of two-chain tPA. Measurements of the plasminogen activation kinetics in the absence of fibrin revealed that tPA-Gly275 possessed a significant intrinsic activity. However, it was 30-fold lower than that of two-chain tPA. Addition of polymerised fibrin profoundly enhanced the plasminogen activation rate of both tPA-Gly275 and wild-type one- and two-chain tPA to approximately the same maximal level. The results were interpreted to mean that fibrin binding can induce an activated state of the intact tPA one-chain form.

Biopolymers↗