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Biomedical subjects

M Lambert

Publications and source records attributed to M Lambert.

At least 415 records · Page 23Linked to original sources

Study of adenine aminohydrolase in the yeast, Schizosaccharomyces pombe.

Observation of the growth of some adenineless mutants of Schizosaccharomyces pombe on six substituted purine analogs leads to the hypothesis that an enzyme is present which catalyzes the conversion of these analogs into hypoxanthine. The enzyme adenase (adenine aminohydrolase, EC 3.5.4.2) has been found to be active in cell-free extracts of S. pombe. Results are reported which are in agreement with the hypothesis that this enzyme is responsible for the in vivo utilization of 6-chloropurine. This evidence comes mainly from a study of adenine aminohydrolase in two mutants selected for partial inability to grow on 6-chloropurine.

Adenine↗

Cardiac functional improvement by a human Bcl-2 transgene in a mouse model of ischemia/reperfusion injury.

BACKGROUND: Apoptosis has been shown to contribute to myocardial reperfusion injury. It has been suggested that, in reducing the apoptotic component within the ischemic area at risk, Bcl-2 overexpression could lead to a ventricular function improvement. METHODS: Transgenic mice overexpressing the anti-apoptotic human Bcl-2 cDNA in heart were subjected to a 1-h left coronary artery occlusion followed by a 24-h reperfusion. At the end of the experiment, left ventricular function was assessed by two-dimensional echocardiography. After sacrifice, the area at risk (AR) and the infarct area (IA) were determined by Evans blue and triphenyltetrazolium chloride staining, respectively. The extent of apoptosis was assessed by the TUNEL method. Non-transgenic littermates served as controls. RESULTS: Baseline AR was not different between Bcl-2 transgenic mice and their wild-type littermates. In contrast, left ventricular ejection fraction was significantly improved in the transgenic mice line (61.25 +/- 4.0%) compared to non-transgenic littermates (43.2 +/- 5.0%, p < 0.01). This functional amelioration was correlated with a significant reduction of infarct size in transgenic animals (IA/AR 18.51 +/- 3.4% vs 50.83 +/- 8.4% in non-transgenic littermates). Finally, apoptotic nuclei were less numerous in transgenic mice than in controls as quantified by TUNEL analysis (8.1 +/- 2.2% vs 20.6 +/- 4.4%). CONCLUSIONS: Bcl-2 overexpression is effective in reducing myocardial reperfusion injury and improving heart function. This benefit correlates with a reduction of cardiomyocyte apoptosis. The apoptotic component of ischemia/reperfusion injury could therefore constitute a new therapeutic target in the acute phase of myocardial infarction.

Animals↗

VAD chemotherapy--toxicity and efficacy--in patients with multiple myeloma and other lymphoid malignancies.

Thirty-three patients with multiple myeloma (11 untreated, 15 refractory and seven relapsed patients) have received vincristine and adriamycin infusion therapy with oral dexamethasone (VAD). The median number of course received was five. In addition 16 patients with lymphoid malignancy have received a median of four courses of VAD. Three patients who relapsed after VAD have received further VAD therapy making 52 patient treatments assessable for toxicity. Ten per cent had nausea, 4 per cent vomiting, 4 per cent total alopecia, 25 per cent constipation, 33 per cent paraesthesiae, 8 per cent proximal myopathy, 33 per cent dyspepsia, 23 per cent proven bacteraemia, and 19 per cent chest infections. Infections were not usually associated with neutropenia. Shingles was seen in four patients with myeloma, but none of the patients with lymphoid malignancy. The response rate in myeloma was 9/11, for previously untreated patients, 3/7 for relapsed, and 8/15 for refractory patients. Responses have been seen in other lymphoid malignancies-1/2 patients with relapsed acute lymphoblastic leukaemia had a complete remission. Two out of seven patients with chronic lymphocytic leukaemia achieved a partial remission, and a further three had a clinical improvement. Three out of six patients with non-Hodgkin lymphoma and one patient with macroglobulinaemia achieved a partial remission.

Adult↗

The use of isoelectric focusing on polyacrylamide gel for the enzymatic analysis of 'Old World' Leishmania species.

Using isoelectric focusing (IEF), a high resolution electrophoresis technique, we analysed 6 enzymes of 24 cloned strains representing all major taxa of 'Old World' Leishmania. The comparison of enzymatic patterns obtained with IEF and starch gel electrophoresis showed that IEF is a more discriminatory and more informative technique for the enzymatic analysis of Leishmania strains; it can detect very slight differences between 2 electromorphs not revealed with starch gel electrophoresis. Moreover, IEF detected several multi-banded patterns which appeared as single bands with starch gel electrophoresis. These multi-banded patterns could not be the result of strain heterogeneity since all the strains had been cloned. Their significance in the biology of Leishmania is discussed.

Animals↗

Analysis of the peripheral T-cell compartment in the MHC class II deficiency syndrome.

To analyse the impact of lack of MHC class II expression on the composition of the peripheral T-cell compartment in man, the expression characteristics of several membrane antigens were examined on peripheral blood lymphocytes (PBL) and cultured T cells derived from an MHC-class-II-deficient patient. No MHC class II expression could be detected on either PBL or activated T cells. Moreover, the expression of MHC class I was reduced both on PBL and in vitro activated T cells compared to the healthy control. However, the reduced expression of CD26 observed on the PBL of the patient was restored after in vitro expansion. Despite the presumably class-II-deficient thymic environment, a distinct but reduced single CD4+ T-cell population was observed in the PBL of the patient. After in vitro expansion, the percentage of CD4+ cells dropped even further, most likely due to a proliferative disadvantage, compared to the single CD8+ T-cell population. However, proliferation analysis showed that T-cell activation via the TcR/CD3 pathway is not affected by the MHC class II deficiency.

Antigens, CD↗

Expression of the transcripts initiated in the 62nd intron of the dystrophin gene.

The pattern of expression of two distal transcripts initiated in the 62nd intron of the dystrophin gene was investigated under different circumstances; (i) during the development of different rat tissues these transcripts and Dp71, a protein encoded by one of them, increased with brain development and decreased with muscle development; (ii) in cultured glial and neuronal cells, the distal promoter was coactivated with tissue-specific upstream promoters, the muscle-type promoter in glial cells and the brain-type promoter in neuronal cells, which suggests that activity of the upstream promoter does not interfere with activity of the distal promoter; (iii) in lymphoblasts of DMD patients with various deletions of the dystrophin gene, the most distal of which included the 56th intron, the production of the distal transcript was not perturbed.

Animals↗

Analysis of deletions in DNA from patients with Becker and Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is an X-linked recessive genetic disorder for which the biochemical defect is as yet unknown. Recently, two cloned segments of human X-chromosome DNA have been described which detect structural alterations within or near the genetic locus responsible for the disorder. Both of these cloned segments were described as tightly linked to the locus and were capable of detecting deletions in the DNA of boys affected with DMD. In an attempt to determine more precisely the occurrence of these deletions within a large population of DMD patients and the accuracy of one of the segments, DXS164 (pERT87), in determining the inheritance of the DMD X chromosome, the subclones 1, 8 and 15 were made available to many investigators throughout the world. Here we describe the combined results of more than 20 research laboratories with respect to the occurrence of deletions at the DXS164 locus in DNA samples isolated from patients with DMD and Becker muscular dystrophy (BMD). The results indicate that the DXS164 locus apparently recombines with DMD 5% of the time, but is probably located between independent sites of mutation which yield DMD. The breakpoints of some deletions are delineated within the DXS164 locus, and it is evident that the deletions at the DMD locus are frequent and extremely large.

Chromosome Deletion↗

Inoculation of lactating ewes by the intramammary route with Mycoplasma agalactiae: comparative pathogenicity of six field strains.

Contagious agalactia affects goats and sheep. In most infected sheep, the causal agent, Mycoplasma agalactiae, induces mastitis and/or agalactia, keratoconjunctivitis and arthritis. However, a few strains of M. agalactiae were isolated from tank milk from flocks without any clinical signs. The present study was undertaken to compare these apparently "asymptomatic" strains to classical virulent strains in order to assess the pathogenicity of four "asymptomatic" strains. Six groups of lactating ewes were inoculated by the intramammary route with 10(8) viable mycoplasmas of each strain. The clinical signs were regularly evaluated; the excretion of bacteria in milk and the serological response were measured. Ewes were necropsied 7 weeks after inoculation and the level of infection in retromammary lymph nodes was determined. Among the 4 apparently "asymptomatic" strains, 2 were fully virulent as were the strains isolated from discased animals, and the other 2 induced somewhat less severe clinical symptoms. The other parameters, in particular the level of excretion in milk and the level of infection of regional lymph nodes following necropsy were similar for all strains. Mean antibody response was also comparable between the apparently "asymptomatic" and virulent strains, in spite of great individual variability. This observation shows that flocks without any clinical sign from which M. agalactiae is isolated in bulk milk, must be kept under strict control since mycoplasmas may induce severe outbreaks later with changing conditions of breeding.

Animals↗

Subjective cognitive dysfunction in first-episode and chronic schizophrenic patients.

Previous studies indicate that first-episode and chronic schizophrenic patients do not differ regarding neuropsychological performance as assessed with standard cognitive tasks. For the present study, it was investigated whether first-episode and chronic schizophrenics report similar subjective cognitive deficits. The Frankfurt Complaint Questionnaire (FCQ), a scale devised for assessing subjective cognitive disturbances in schizophrenia, was administered to 20 first-episode and 36 chronic schizophrenic patients, as well as 20 healthy controls. The schizophrenic subsamples did not differ on any of the FCQ subscales or on a "lie scale," measuring illness denial. Psychopathological ratings were comparable for both groups. As expected, healthy subjects reported significantly less cognitive and perceptual problems than schizophrenic patients. In marked contrast to a Kraepelinian view of schizophrenia, the present data confirm previous studies conducted with objective neuropsychological tests that schizophrenia is a neurodevelopmental rather than a neurodegenerative disorder.

Adult↗

Jan Fryderyk Knolle's forgotten dissertation on osseous syphilis, 1763.

In 1763 Jan Fryderyk Knolle, a Polish physician, wrote his doctoral thesis on osseous syphilis, De Ossium Carie Venerea, at the University of Leipzig, Saxony (now East Germany). Knolle described the pathology, clinical picture, and treatment of syphilis of the bones and emphasized the severity and destructiveness of bony lesions, which could occur even in the early stage of the disease. An interesting and detailed drawing showing osteomyelitis of the femur, which appears to be of syphilitic origin, was included in Knolle's dissertation. This illustration is an example of 18th century syphilologic iconography. A comparison of the clinical picture of syphilis as described by Knolle with that of the present day suggests that syphilis has become a milder disease.

Bone Diseases↗