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Biomedical subjects

B Diez

Publications and source records attributed to B Diez.

10 recordsLinked to original sources
PubMed1992

Molecular epidemiology of Burkitt's lymphoma from South America: differences in breakpoint location and Epstein-Barr virus association from tumors in other world regions.

We have previously shown that the endemic (African) and sporadic (North American) forms of Burkitt's lymphoma (BL) differ at a molecular level. We have now extended our studies to the molecular epidemiology of BL in South America, specifically to two climatic regions: temperate (Argentina and Chile) and tropical (Brazil). We have examined the patterns of chromosomal breakpoint locations in 39 tumors with respect to geography and Epstein-Barr virus (EBV) association. The result of these analyses provide further support for the existence of pathogenetically distinct subtypes of BL in different world regions. The majority of breakpoints on chromosome 8 in South American BL (41%) occurred in the immediate flanking region of c-myc, ie, further 5' of the "typical" sporadic breakpoints, in the first exon/intron region, and further 3' of the "typical" endemic breakpoints, which are usually distant from c-myc. However, the distribution of breakpoints on chromosome 14 in tumors from the temperate and tropical regions of South America is similar to that observed in sporadic and endemic tumors. Interestingly, only one tumor with an unrearranged c-myc gene joined to the S mu region of chromosome 14 was observed. This combination was also rarely observed in our earlier series and presumably is either less readily generated by the mechanism that mediates 8;14 translocation or requires other, infrequent genetic changes to provide the necessary selective advantage for lymphomagenesis. The frequency of EBV association in South American BL (51%) is also intermediate with respect to tumors from the United States (30%) and Africa (100%). No correlation with the breakpoint location on chromosome 8 was discernable. Surprisingly, only 54% of tumors with breakpoint outside c-myc were EBV positive. This is in contrast to endemic tumors and suggests that any pathogenetic contribution of EBV is not dependent on breakpoint location, but is more likely to complement additional pathogenetic elements that differ in different world regions.

Adolescent↗
PubMed1989

Thyroid dysfunction in Hodgkin's disease.

Radiotherapy to the neck and/or polychemotherapy late effects on the thyroid were investigated in 51 patients (34 males and 17 females) with Hodgkin's disease. Except for two untreated, recently diagnosed patients, all were studied after 1 to 105 months (median, 27.5 months) of completion of polychemotherapy. Age ranged from 6.2 to 36.6 years (median, 13.6 years). Patients were divided according to treatment into four groups: (A) patients treated with CVPP (cyclophosphamide, vinblastine, procarbazine, and prednisone); (B) 22 patients treated with CVPP plus radiotherapy (median radiation dose to the thyroid, 3000 cGy); (C) seven patients with ACOP/BVP (adriamycin, cyclophosphamide, vincristine, prednisone, bleomycin, vinblastine, procarbazine); and (D) seven patients treated with different polychemotherapy protocols, four of whom also received radiotherapy. Elevated basal and/or post-TRH, -TSH levels were found in the following: Group A: two of 12 patients (17%); Group B: 11 of 22 (50%); Group C: four of seven (57%); and Group D: two of seven (28%). Positive antimicrosomal thyroid antibody titers (AM Ab) were found in the following: Group A: three of 12 patients (25%); Group B: six of 21 (28%), Group C: two of seven (28%); and Group D: one of six (17%). Of 46 patients studied, 12 (26%) had positive AM Ab; 37 of 46 patients were younger than 20 years of age, 11 (30%) of whom had positive AM Ab versus 4% in the normal population (P less than 0.001). Two recently diagnosed, untreated patients had either high TSH response to TRH or positive AM Ab. In conclusion, higher frequency of thyroid dysfunction was observed in patients receiving radiotherapy (50% versus 27%). Prevalence of positive AM Ab, apparently unrelated to therapy, was higher in young patients than in the normal population. A predisposition to autoimmune thyroid disease seems to be present in these patients, but it is not possible to discern how lymphoma and thyroiditis are interrelated.

Adolescent↗
PubMed1989

Relationship between the production of interferon-alpha/beta and interferon-gamma during acute toxoplasmosis.

Acute toxoplasmosis was induced in mice, and interferon (IFN) production in serum and by spleen cells was evaluated during the infection period. Interferon was characterized by acid-treatment and anti-IFN-alpha/beta neutralization. In order to verify the correlation between the unusual aspects of the IFN production and the induction of immunosuppression, splenocyte mitogen responsiveness was investigated concomitantly to IFN synthesis. The activity of Toxoplasma-induced serum IFN-alpha/beta increased gradually throughout all post-infection days, but IFN-gamma was not detected in the systemic circulation at any time during the infection. It was also observed that IFN-alpha/beta production and the capacity to produce IFN-gamma by spleen cells were closely and inversely correlated. As the infection progressed, more IFN-alpha/beta was produced, and the ability of spleen cells to produce IFN-gamma decreased. The observation that Toxoplasma-infected mice were concomitantly immunosuppressed (as documented by mitogen unresponsiveness and defective IFN-gamma production) in direct correlation to IFN-alpha/beta production, suggests that such IFN-alpha/beta production is an important factor associated with acute toxoplasmosis-induced immunosuppression.

Acute Disease↗
PubMed1989

Malignant germ cell sacrococcygeal tumors in children. Improved prognosis after introduction of cisplatin-containing multiple drug treatment.

The survival of children with malignant germ cell sacrococcygeal tumors has improved during the last few years after introduction of a multidrug protocol including cisplatinum. Treatment for 10 patients registered in 1965-1978 was not uniform and consisted of surgical resection or biopsy and radiotherapy with or without multiple drug chemotherapy (methotrexate + actinomycin D + cyclophosphamide). Only one of these patients is alive. Fifteen patients registered between 1978 and 1986 were treated with actinomycin D + cyclophosphamide + vincristine + doxorubicin + bleomycin + cisplatinum. Four patients also received radiotherapy. Seven out of these 15 children are alive without evidence of disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Glucokinase-deficient mutant of Penicillium chrysogenum is derepressed in glucose catabolite regulation of both beta-galactosidase and penicillin biosynthesis.

One glucokinase-deficient mutant (glk1) of Penicillium chrysogenum AS-P-78 was isolated after germ tube-emitting spores were mutated with nitrosoguanidine and selected for growth on lactose-containing medium in the presence of inhibitory concentrations of D-2-deoxyglucose (3 mM). Penicillin biosynthesis was greatly reduced (55%) in D-glucose-grown cultures of the parental strain, but this sugar had no repressive effect on the rate of penicillin biosynthesis in the mutant glk1. This mutant was deficient in ATP-dependent glucokinase and showed a greatly reduced uptake of D-glucose. The parental strain P. chrysogenum AS-P-78 showed in vitro ATP-dependent phosphorylating activities of D-glucose, D-2-deoxyglucose, and D-galactose. The glk1 mutant was deficient in the in vitro phosphorylation of D-glucose and D-2-deoxyglucose but retained a normal D-galactose-phosphorylating activity. D-Glucose repressed both beta-galactosidase and isopenicillin-N-synthase but not acyl coenzyme A:6-aminopenicillanic acid acyltransferase in the parental strain. The glucokinase-deficient mutant was simultaneously derepressed in carbon catabolite regulation of beta-galactosidase and isopenicillin-N-synthase, suggesting that a common regulatory mechanism is involved in carbon catabolite regulation of both sugar utilization and penicillin biosynthesis.

Carbon↗
PubMed1987

Long-term endocrine sequelae after surgery, radiotherapy, and chemotherapy in children with medulloblastoma.

Thirteen children with medulloblastoma, were studied after 2 to 62 months off radiotherapy and chemotherapy with methotrexate and BCNU. Ages at time of study ranged from 2.3 to 15.7 years. Eleven patients, followed for a mean of 22 months, showed a significant decrease of height score, whereas nine patients had deficient growth hormone (GH) response to provocative tests. Clinical pubertal progression was normal in all patients, and three of five girls with advanced pubertal development had menarche. No evidences of gonadotropin disturbances were found in five patients whereas seven had raised basal follicle-stimulating hormone (FSH) level or FSH response to luteinizing hormone-releasing hormone (LH-RH). Abnormalities in thyrotrophin (TSH) secretion were found in 9 of 13 patients. This study shows that poor growth and GH deficiency were frequent in our patients. The high frequency of thyroid disturbances observed point out the need of evaluating thyroid function for adequate replacement therapy. Perhaps modification of adjuvant chemotherapy in the future can diminish drug-induced gonadal damage.

Adolescent↗
PubMed1986

Paratesticular rhabdomyosarcoma in children.

The clinicopathological features of 10 children with paratesticular rhabdomyosarcoma treated between 1965 and 1984 are reviewed. Of the patients 9 had embryonal rhabdomyosarcoma and 1 was pleomorphic. Median age was 4 years (range 2 to 11 years). Staging was based on clinical findings, chest x-ray, lymphoangiography, computerized tomography and histological studies. The disease was stage I in 5 patients, stage II in 2 and stage IV in 3. Treatment included radical orchiectomy in all patients, chemotherapy in 8 and lumboaortic radiotherapy in 5. No retroperitoneal node lymphadenectomy was performed. Of the 10 children 7 are free of disease after 2 to 19 years (median 7 years) of followup, including all of those with stages I and II disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Primary rhabdomyosarcoma of brain and cerebellum. Report of four cases in infants: an immunohistochemical study.

Tumors of the central nervous system (CNS) composed of pure mesenchymal derivatives with both embryonal and mature striated muscle cells devoid of neuroblastic elements should be considered rhabdomyosarcomas. Some 13 cases have been reported, and here we study four additional cases in infancy under 3 years of age which represent 0.82% of 483 intracranial tumors studied by us at the Children's Hospital in the last 12 years. Two cases were localized in the temporal lobes, and two were in the cerebellar vermis. All of them were typical embryonal rhabdomyosarcomas at various stages of differentiation including undifferentiated mesenchymal cells, embryonal cells, and rhabdomyoblasts. Tumor cells achieved a higher degree of differentiation in the cerebellum, as shown by readily detectable immature muscle fibers which were consistently absent in tumors involving the brain. Myoglobin [peroxidase-antiperoxidase (PAP) technique] was positive throughout in rhabdomyoblasts and in immature muscle cells, whereas glial fibrillary acidic protein was negative in all four tumors. In spite of the well differentiated appearance of the cerebellar tumors, their behavior was highly malignant with extensive infiltration of brainstem leptomeninges in one case, and all patients survived for only a short time after surgery. These tumors may be observed in the midline structures of the posterior fossa and in the brain, but we suspect their true incidence might be higher if immunohistochemical techniques were applied.

Brain Neoplasms↗