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Biomedical subjects

G Brusa

Publications and source records attributed to G Brusa.

At least 19 recordsLinked to original sources
PubMed2001

Expression of P21(WAF1/CIP1/SID1) cyclin-dependent kinase inhibitor in hematopoietic progenitor cells.

P21(Waf1/Cip1/Sid1) is a critical component of biomolecular pathways leading to the G(1) arrest evoked in response to DNA damage, growth arrest signals and differentiation commitment. It belongs to the Cip/Kip class of cyclin-dependent kinase inhibitors and is at least partly regulated by p53. P21(Waf1/Cip1/Sid1) functional inactivation possibly resulting from mutations of the gene itself or, more likely, from p53 mutations may be critical for either the cell fate following DNA-damaging insults or clonal evolution toward malignancy. In the study presented here we describe a competitive polymerase chain reaction (PCR) strategy whose sensitivity and reproducibility enable us to attain a precise quantitation of p21(Waf1/Cip1/Sid1) expression levels in hematopoietic progenitors, the cell compartment which mostly suffers from the side effects of genotoxic drugs in use for cancer cure. The strategy was set in the M07 factor-dependent hematopoietic progenitor cell line. We confirmed that its p21(waf1/cip1/sid1) constitutive expression level is very low and up-modulated by DNA-damaging agents: ionizing radiations and ultraviolet light. Gene up-modulation resulted in checkpoint activation and, in particular, in a significant G(1) arrest, required for either the repair of damaged DNA sequences or apoptotic cell death. Our competitive PCR strategy was further validated in CD34(+) purified hematopoietic progenitors from healthy donors mobilized into the peripheral blood by granulocyte colony-stimulating factor and intended for allogeneic bone marrow transplantation. The constitutive p21(WAF1/CIP1/SID1) expression levels, measured in three separate harvests, were very low and no significant differences were apparent. Our results support the use of a competitive PCR strategy as a useful tool for clinical purposes, to assess the individual biomolecular response of early hematopoietic progenitors to antiblastic drugs.

Cell Cycle↗
PubMed2001

Competitive polymerase chain reaction as a method to detect the amplification of bcr-abl gene of chronic myeloid leukemia.

BACKGROUND AND OBJECTIVES: The chimeric product of the bcr-abl rearranged gene is critical in the pathogenesis of chronic myeloid leukemia (CML), yet its role in the progression of the disease remains unclear. There is some evidence that increased bcr-abl expression levels, possibly due to gene amplification, precede the clonal evolution of CML hematopoietic progenitors toward a fully transformed phenotype and might be involved in their resistance to interferon-alpha or tyrosine kinase inhibitors. DESIGN AND METHODS: To quantify the bcr-abl gene both at the genomic and at the transcriptional levels we developed a competitive polymerase chain reaction (PCR) strategy. The competitive PCR technique is based upon the co-amplification of the sample template (target) together with increasing amounts of a DNA fragment (competitor) sharing with the target the primer recognition sites, but differing in size. We constructed a competitor for the quantification of both b2a2 and b3a2 alternative splicing forms of the bcr-abl chimera and established the accuracy and reproducibility of our competitive strategy in a clone of the murine 32DG hematopoietic cell line (32D LG7), which bears a stable integration of a single copy of p210 bcr-abl fusion gene. We utilized this technique to follow, over a period of 200 days, the fusion gene copy numbers and transcription rates in several p210 bcr-abl-transduced 32D cell clones, an experimental condition mimicking the evolution of CML myeloid progenitors in vivo. RESULTS: Our results are consistent with p210 bcr-abl overexpression but not gene amplification associated with their clonal evolution. Increased p210 bcr-abl transcription rate is associated with the abrogation of radiation-induced apoptotic cell death, suggesting a role for the chimeric gene expression level in cell life expectancy after a genotoxic insult. INTERPRETATION AND CONCLUSIONS: We conclude that the assessment of gene amplification and expression might serve to improve prognostic classification and follow-up of CML patients.

Alternative Splicing↗
PubMed1993

Wernicke-Korsakoff Encephalopathy Following Biliopancreatic Diversion.

Wernicke-Korsakoff disease with sensory-motor neuropathy was diagnosed in three out of a series of 1,663 patients (0.18%), with onset 2, 3 and 5 months after biliopancreatic diversion. Precipitating factors were vomiting, minimal food intake, anorexia, rapid weight loss, and glucose-containing intravenous feeding. Recovery was partial in two and complete in one of the patients. In the early postop, prophylactic thiamine should be given to the patients with excessively limited eating capacity. Larger doses of thiamine should be instituted parenterally either in the case of suspected Wernicke-Korsakoff encephalopathy or before starting feeding for protein malnutrition.

Journal Article↗
PubMed1990

Scinticisternography in presenile and senile degenerative disease.

86 patients suffering from various senile and presenile degenerative diseases were studied using scinticisternography with In111-DTPA. Flow reversal and delayed clearance were observed in 62 of these patients. These alterations, possibly related to the cerebrospinal fluid dynamics, show the aspecificity of the SC picture. The SC picture does not seem to be correlated to the clinical signs.

Aged↗
PubMed1990

Thyrotoxic encephalopathy and recurrent seizures.

Epilepsy is a rare but possible manifestation of thyrotoxicosis. The patient reported here developed recurrent, generalized and focal seizures, as presenting symptoms of a thyrotoxic encephalopathy. Intercritic EEG records showed triphasic waves. Seizures and signs of encephalopathy disappeared and the EEG reverted to normal only after treatment of the thyroid hyperfunction. It is concluded that thyroid function should be evaluated in cases of otherwise unexplained encephalopathy with untreatable seizures and triphasic waves.

Adult↗
PubMed1988

Spinal cord softenings of identifiable cause: anatomical and clinical features.

To complete our bibliographic review of spinal cord softenings, we now discuss the clinical and pathological findings in the cases of known or probable cause. Comparison of the diagnostic groups yields some differences in respect of sex, age and mode of onset, survival and extent of the anatomical lesion. Further differences, especially in age at onset, clinical pattern and lesion site, emerge from a comparison of these cases of known or probable cause with those whose cause is not apparent.

Aged↗
PubMed1988

Recurrent vascular myelopathy. Report of a case with autopsy.

A case of ischemic myelopathy which was marked by two clinical episodes, separated by a 4-month interval and affecting the same level of the spinal cord, is reported. A wide-ranging search through the literature shows that the recurrent type of ischemic vascular myelopathy is very rare.

Aged↗
PubMed1987

Some little-known aspects of spinal cord softening.

311 cases of spinal cord softening, were selected for review. The following points emerged from this study: 1) spinal cord softening is a rare occurrence; 2) while formerly syphilis was the most frequent cause, recently reports of cases secondary to aortic disease or to embolism with diffuse signs of arteriosclerosis and circulatory failure pointing to a different pathogenesis have become more frequent; 3) the site of softening rarely corresponds to the vascular spinal territories as defined by the anatomists, from which it may be argued that often several arterial territories may be involved simultaneously or, alternatively, that the arterial territories are not so rigidly defined as anatomical research has led us to suppose; 4) the few cases of multiple vascular lesions show that, as happens in the brain, the cord may be damaged contemporaneously or successively in several areas.

Adolescent↗
PubMed1987

Electrophysiological analysis of motor control in patients with vascular hemichorea.

An EMG analysis of motor control was performed in 4 patients with unilateral choreic movements of sudden onset, 3 of whom presented CT scan evidence of lacunar infarcts involving the contralateral striatum. The choreic dyskinesias were correlated with EMG bursts of variable duration occurring with a random order of activation. Ballistic elbow flexion movements were performed with a normal triphasic EMG pattern, but both size and duration of the first agonist burst were increased on the affected side. Abnormalities of cerebral somatosensory evoked responses were observed in 3 patients on stimulation of the side with choreic movements.

Aged↗
PubMed1986

Long-term prognosis of patients with lacunar syndromes.

A follow-up study of 107 patients with lacunar syndromes has been performed using the analysis of the survival curves and the recurrence curves for new focal cerebrovascular acute episodes. At the end of the 7th year of follow-up, the survival rate of lacunar patients was 479 per 1000, lower than the survival rate of the normal population matched for sex and age (755 per 1000). A more severe prognosis was observed in subjects over 65 years of age, in patients with pseudobulbar syndrome, hypertension and higher degree of disability. The average recurrence rate for new cerebrovascular episodes was 4.74 per 100 patient-years, much lower than that in survivors from cerebral infarction.

Age Factors↗