Biomedical subjects

E Jaros

Publications and source records attributed to E Jaros.

At least 55 records · Page 3Linked to original sources

PubMed1997

Striatal dopaminergic loss without parkinsonism in a case of corticobasal degeneration.

Neurochemical analyses of post-mortem brain from cases of corticobasal degeneration are extremely rare although nearly 100 cases have been reported in the literature. We detail findings of neurotransmitter derangement in the basal ganglia of a case of neuropathologically confirmed corticobasal degeneration, who presented with dementia. The implications of severe neuronal loss in the substantia nigra and extremely low levels of dopamine and its metabolites in the striatum are considered in relation to the absence of an intrinsic extrapyramidal syndrome.

Acetylcholinesterase↗

PubMed1996

P53 overexpression in head and neck carcinoma and radiotherapy results.

PURPOSE: P53 gene mutations are the common genetic changes encountered in human cancers, and there is extensive evidence that the P53 status may determine tumor response to therapy. This study was carried out to investigate whether there is any correlation between accumulation (overexpression) of P53 protein and poor prognosis in patients with head and neck carcinomas treated with radical radiotherapy. METHODS AND MATERIALS: Seventy-nine patients with head and neck carcinomas who were diagnosed and treated in 1989-90 with curative radiotherapy were studied retrospectively. Paraffin sections from archival material were studied using immunohistochemical staining (IHC) with mouse monoclonal antibodies (D0-7) to human P53 protein. Univariate and multivariate analysis of loco-regional tumor control and patient survival were performed on possible prognostic factors. RESULTS: Forty-two (53%) patients showed positive IHC staining in their tumors. Fifty-three percent of the laryngeal, 64% of the oropharyngeal, and 43% of the oral cavity carcinomas showed P53 overexpression. All tumor specimens with vascular, lymphatic, and/or sarcolemmal invasion showed P53 overexpression. The proportion of tumor-stained nuclei was higher in the poorly differentiated than in the well and moderately differentiated tumors (p < 0.05), but there was no correlation with the patient overall or disease-free 5-year actuarial survival. There was no difference in the 5-year actuarial survival and disease-free survival between patients with P53 immunostaining in their tumors and those with no immunostaining (59% vs. 65% and 57% vs. 51%, respectively). The TNM tumor stage was the most significant prognostic factor with 5-year actuarial survival of 87% for early and 14% for late stages (p << 0.0001). There was a significant correlation between immunostaining and history of smoking (p = 0.02). CONCLUSION: The data demonstrate that the P53 accumulation as detected by immunohistochemical staining in a group of head and neck carcinomas was not predictive of patient's poor survival or disease-free survival. Multivariate statistical analysis showed that the TNM tumor stage was the only significant prognostic factor. There was a significant association between P53 accumulation and smoking.

Adult↗

PubMed1995

Prognostic significance of the c-erbB-2 oncogene product in childhood medulloblastoma.

The expression and prognostic significance of the c-erbB-2 oncogene product was studied in 55 cases of childhood medulloblastoma. Forty-six of the 55 tumours (83.6%) expressed the c-erbB-2 product. The percentage of tumour cells expressing the c-erbB-2 product proved to be a significant indicator of patient outcome when analysed as both a categorical and a continuous variable. As a categorical variable, patients with more than 50% positive tumour cells had a significantly worse survival, with only 10% alive at 10 years vs 48% for those with less than 50% positive tumour cells (log rank P = 0.0049). To demonstrate that this observed prognostic significance was both independent and not a result of 'data-driven' categorisation, it was also entered into the Cox model as a continuous variable. Prognostic significance was retained in P = 0.038.

Adolescent↗

PubMed1995

Accumulation of wild-type p53 in meningiomas.

The p53 tumour suppressor gene contributes to the regulation of DNA repair and the initiation of apoptosis. Mutations of this gene and nuclear accumulation of its protein product are features of a large variety of tumours. A histological spectrum of meningiomas, including anaplastic examples and a meningosarcoma, was analysed for accumulation of the p53 protein and mutations in exons 4-9 of the p53 gene. No mutations were found, but 9/34 (26%) tumours showed accumulation of the p53 protein. The p53-positive meningiomas came from across the histological spectrum and were not restricted to the anaplastic group. The accumulation of wild-type p53 in a proportion of meningiomas may reflect this gene's role in DNA repair, or its enhanced stability when bound to cellular proteins such as the mdm-2 gene product.

Antibodies, Monoclonal↗

PubMed1993

p53 protein overexpression identifies a group of central primitive neuroectodermal tumours with poor prognosis.

Primitive neuroectodermal tumours (PNET's) or medulloblastomas are common primary brain tumours of childhood. Current treatment protocols achieve 50-60% cures. However, it has proved difficult to develop better treatment for the remaining patients because prognostic factors are not established. We have investigated the prognostic value of p53 protein expression in 87 PNET's using immunohistochemistry with DO-7 and CM-1 antibodies on biopsy paraffin sections. Eight patients (9%) had intensely reactive tumour cell nuclei, and a significantly reduced survival (P = 0.002); only one survives and this with a recurrent tumour 50 months following diagnosis. Sixty eight per cent of patients had faintly reactive tumour cell nuclei, a reduced survival up to 4 years but a long term survival not significantly different (P = 0.41) from 23% of patients with p53 negative PNET's; the 10 year survival rates were 37% and 40%, respectively. Males had a reduced survival (P = 0.04) with a 2-fold relative risk of death compared to females. Multivariate analysis showed that intense overexpression of p53 protein identifies a group of PNET patients with a 7-fold relative risk of death compared to all other cases, irrespective of sex. This marked difference suggests the involvement of p53 in the pathogenesis of PNET's which have a particularly poor response to treatment, and should help to develop new therapies for this group of patients.

Adolescent↗

PubMed1992

Prognostic implications of p53 protein, epidermal growth factor receptor, and Ki-67 labelling in brain tumours.

The expression of p53 protein, epidermal growth factor receptor (EGFR), and Ki-67 nuclear antigen was examined by immunohistochemistry in biopsies of 16 types of human brain tumours, including 43 astrocytomas. P53 protein, almost certainly its mutant form, was expressed in seven of the 16, and EGFR in 11 of the 16 types of tumours. In astrocytomas both the proportion of tumours which expressed p53 or EGFR increased with grade of malignancy as did the mean Ki-67 labelling index (LI): p53-0% in grade 1, 17% in grade 2, 38% in grade 3, 65% in grade 4; EGFR-0% in grade 1, 33% in grade 2, 85% in grade 3, 95% in grade 4; mean Ki-67 L1-1.1% in grades 1 and 2, 8.3% in grade 3, and 13.4% in grade 4. Astrocytomas which expressed p53 or EGFR had a significantly higher Ki-67 LI at P less than 0.05 (11.8% and 10.7%, resp.) than those that did not (6.2% or 4.1%, resp.). Patients with astrocytomas expressing p53 or EGFR had a significantly reduced survival (P = 0.035 and P = 0.007, resp.): only 11% of the p53 + ve and 13% of the EGFR + ve patients were alive at 100 weeks following diagnosis compared to 36% of p53-ve or 60% of EGFR-ve patients. Patients with Ki-67 LI greater than 5% had a reduced survival (P less than 0.0001)--none survived beyond 86 weeks following diagnosis, whilst 63% of patients with less than 5% positive cells were still alive at 100 weeks. The univariate analysis showed that in astrocytomas expression of p53 mutants, EGFR protein, and Ki-67 greater than 5% are associated with malignant progression and poor prognosis. The multivariate analysis revealed that only tumour grade and Ki-67LI were independent prognostic factors for survival.

Adolescent↗

PubMed1990

[Cryotherapy of an inoperable breast tumor].

The use of cryocauter in inoperable tumor of breast is described. Case-reports are presented of successful approach by cryolysis prior to the final lobe plastic.

Adenocarcinoma, Scirrhous↗

PubMed1989

Effects of tenotomy on muscle histology and energy metabolism in normal and dystrophic mice.

Creatine, phosphocreatine, ATP and phosphate concentrations were measured in extracts of tibialis anterior and gastrocnemius muscles from 42 normal and 39 dystrophic mice from 1 to 16 weeks of age. No differences were observed at 1 week, prior to the onset of histological abnormalities in dystrophic animals. Creatine and phosphocreatine concentrations were significantly reduced in older dystrophic mice, and phosphate levels were higher, while ATP levels generally did not differ. Tenotomy of gastrocnemius at 1 week prevented the development of dystrophy in this muscle but this was not associated with an increase in phosphogen concentrations. Serum creatine kinase levels were significantly higher in dystrophic mice than normal mice but only during the first two weeks of life; levels in older mice were not significantly different. This study shows that the reported deficits in phosphogen concentrations in dystrophic muscles are likely to reflect the results, rather than the cause, of the dystrophic process.

Age Factors↗

PubMed1988

Ultrastructure of the skeletal muscle in the X chromosome-linked dystrophic (mdx) mouse. Comparison with Duchenne muscular dystrophy.

Ultrastructurally there are some clear differences in the pathology of muscle in X chromosome-linked muscular dystrophy of the mouse (mdx) and Duchenne muscular dystrophy (DMD). In particular the mouse muscle does not become infiltrated by large aggregations of connective tissue. It has been proposed that the differences are due to secondary biochemical changes consequent on the absence of dystrophin in both conditions. If this is the case, attention should be directed to the earliest ultrastructural changes held in common by both disorders. The most conspicuous of these, preceding myofibril breakdown, is dilation of the sarcoplasmic reticulum. Any physiological link between this and the absence of dystrophin remains to be determined. We suggest that in the mdx mouse, the widespread myofibre necrosis occurring at 3-4 weeks is triggered by increased mechanical demands causing the lack of dystrophin to become critical at this time. Subsequent regeneration of the myofibres appears to be almost completely successful. The ultimate failure of regeneration in DMD, in contrast, may be due to an additional factors acting in DMD exacerbating the lack of dystrophin. This additional factor may be associated with the plasma membrane lesions (not seen in mdx). Alternatively there may be factors present in the mouse that compensate for the lack of dystrophin. It is pointed out that to understand better the different processes occurring in mdx and DMD we need to learn more about the factors which control the balance between the growth of muscle and the growth of connective tissue in both normal and pathological human and mouse muscle.

Animals↗

PubMed1986

Spontaneous electrical activity in muscles of dystrophic (dy/dy) mice.

Spontaneous electrical activity of tibialis anterior (TA) muscles was recorded using extracellular electrodes in dystrophic and phenotypically normal mice. Abnormal levels of spontaneous activity were recorded in the muscles of adult dystrophic mice. The activity was reduced by more than 75% after sciatic nerve section in anaesthetised dystrophic mice suggesting that most of the activity was neurally mediated. No abnormal activity was seen in the biceps brachii muscles of adult dystrophic mice. No abnormal spontaneous activity was seen in young (2-3-week-old) dystrophic mice. As degeneration of muscle fibres begins at about 7 days of age in dystrophic hindlimb muscles, the onset of the abnormal spontaneous EMG activity could not be considered causally related to muscle fibre degeneration.

Age Factors↗

PubMed1984

A developmentally regulated disappearance of slow myosin in fast-type muscles of the mouse.

Histochemistry and immunocytochemistry using an antibody to adult rat slow-type myosin demonstrated that about 10% of the fibers in the mouse extensor digitorum longus and semimembranosus muscles contain slow myosin during the first month after birth. In adult animals, these muscles have only 0-08% slow myosin-containing fibers. These results demonstrate a developmentally linked disappearance of an adult-type myosin, and show that the adult phenotype of muscle fibers is not necessarily determined before birth as previously suggested.

Animals↗

PubMed1983

Quantitative studies of the abnormal axon-Schwann cell relationship in the peripheral motor and sensory nerves of the dystrophic mouse.

The nature and extent of abnormal axon-Schwann cell relationships in peripheral portions of dystrophic motor and sensory nerves were quantitatively evaluated between 1 and 9 months of age using teased fibres and electron micrographs. The results show that in the dystrophic (dy/dy) common peroneal (CPN) and tibial nerves (TN), and less in the dy/dy sural nerve (SN): (1) the number of Schwann cell nuclei associated with myelinated axons is increased with respect to normal; (2) the average internodal length is correspondingly reduced; (3) the average dystrophic internode elongates roughly in parallel with the average normal internode, and with the dystrophic limb; the longitudinal growth of the dystrophic limb is normal; (4) the variation of internodal length is greater than normal; it does not increase with age; (5) the incidence of the nodes of Ranvier which are wider than the normal 3 micrometers limit does not increase with age; and (6) the number of myelinated axons is reduced in the dy/dy CPN and TN but not in the dy/dy SN; it shows no change with age. These data indicate that: (1) in the dy/dy peripheral nerves (PNS) the abnormal axon-Schwann cell relationships and the reduced number of myelinated axons have been established prior to 1 month of age, thereafter progressive degenerative processes do not appear to take place, and (2) the dy/dy sensory nerves are less affected than the motor ones.

Animals↗

PubMed1983