Intrafamilial heterogeneous clinical presentation of the mitochondrial 3243 MELAS mutation; molecular investigations among four generations

We have identified the A3243G heteroplasmic point mutation in mitochondrial DNA from a female patient with headache as the main clinical feature. The mitochondrial origin of her disease was only suspected because of her brother with MELAS syndrome. Morphological and biochemical studies failed to reveal mitochondrial respiratory chain dysfunction in her muscle which contained 65% of mutated mitochondrial DNA molecules. Molecular studies performed among four generations (in the blood of seven subjects) showed the variable transmission of mutated molecules and pointed out the difficulty in giving genetic counsel.     

To what extent does IQ 'explain' socio-economic variations in function?

Background  

The aims of this study were to examine the extent to which higher intellectual abilities protect higher socio-economic groups from functional decline and to examine whether the contribution of intellectual abilities is independent of childhood deprivation and low birth weight and other socio-economic and developmental factors in early life.     

Allergy and occupational exposure to hydroquinone and to methionine.

Respiratory manifestations have been reported after exposure to hydroquinone and to methionine. One hundred and three men in the same chemical plant were divided into three groups according to their exposure and compared by questionnaire, respiratory functional tests with methacholine then salbutamol challenges, and measurements of serum immunoglobulins G and E. Group H included 33 workers exposed to hydroquinone, trimethyl-hydroquinone, and retinene-hydroquinone. Group M included 15 workers exposed to methionine. Group C was a control group of 55 workers. The prevalence of respiratory symptoms was higher in the two exposed groups. Before challenges, pulmonary function values were significantly lower in groups H and M than those in group C. The challenges induced significant variations in the three groups but these variations were less pronounced in group M than in the other groups. The level of immunoglobulin G in group H (m +/- SD = 12.5 gram/liter +/- 2.6) was significantly higher than in group C (10.6 gram/liter +/- 2.4; p less than 0.002). The level of immunoglobulin E in group H (m = 140 IU/l) was also higher in group C (109 IU/l) but this difference was not significant. These findings suggest that exposure to methionine and to hydroquinone and its derivatives induce ventilatory impairment, perhaps by an immunological mechanism.     

Discordant repeat size and phenotype in Kennedy syndrome

Previous reports in the literature have described correlation of increasing repeat length with severity of the phenotype, in Kennedy syndrome. We describe male siblings with different repeat lengths, with lack of expression of the phenotype in the sibling with the longer repeat length. The phenotype was identical to motor neurone disease. There is variability of expression in Kennedy syndrome and repeat length even in siblings cannot be taken as a conclusive indicator of severity. CAG repeat length cannot be used to predict the natural history of Kennedy disease. The diagnosis of Kennedy syndrome should be considered in male patients presenting with atypical motor neurone disease.     

Disorders of the pyruvate dehydrogenase complex

Pyruvate dehydrogenase deficiency may be a non-specific consequence of many different neurological degenerative disorders. There are also serious methodological problems in estimating the activity of this enzyme complex.     

Mitochondrial function and mitochondrial DNA in a series of 64 patients suspected of having mitochondrial myopathy

Biochemical results concerning 64 patients suspected of mitochondrial myopathies are presented. Four clinical groups were studied including 21 encephalomyopathies, 42 ocular myopathies, 8 isolated myopathies and 3 cardiomyopathies. In 26 cases, the coexistence of a normal mitochondrial DNA and a mutated mitochondrial DNA (heteroplasmy) was found (19 simple deletions, 4 multiple deletions and 3 punctual mutations) and all cases presented with ocular disorders (excepted 2 cases with MERRF). Furthermore, 1 complex I deficiency (1 ocular myopathy), 1 complex IV deficiency (1 adult encephalomyopathy type Leigh), 3 complexes I + IV deficiencies (2 cases with a cardiomyopathy and 1 familial MELAS) and 2 pyruvate (1 adult from of Leigh's encephalomyopathy) dehydrogenase deficiencies (clinically and genetically different) did not show evidence of mitochondrial DNA mutation.     

INTERFERONS IN ONCOLOGY

SUMMARY The interferons are natural glycoproteins secreted in response to various stimuli, including viral infection. They have antiviral, antiproliferative and immunomodulatory effects on different target cell populations. Since recombinant human interferons have become available, they have been tested in a wide range of malignancies. They are well established in the treatment of hairy cell leukaemia, chronic myelogenous leukaemia and multiple myeloma. Although they have documented activity against lymphoma, melanoma, renal cell cancer and carcinoid tumours, their role in the treatment of these tumours is less clear. In the common solid tumours, such as lung cancer and colorectal cancer, the use of interferons remains experimental. Here we will summarise their practice applications in oncology, using randomised studies where available to establish their place in multi-modality treatment. We will not discuss their use as antiviral or immunomodulating agents in viral and autoimmune diseases, multiple sclerosis or after organ transplantation.