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Biomedical subjects

B Ramot

Publications and source records attributed to B Ramot.

At least 19 recordsLinked to original sources

Superior vena cava syndrome associated with lymphoma.

OBJECTIVE: To evaluate the workup and treatment of children with lymphoma and superior vena cava syndrome. DESIGN: A retrospective survey. SETTING: State hospital serving as a secondary and tertiary referral center for pediatric oncology and pediatric cardiac surgery. PARTICIPANTS: Eleven children aged 11 months to 12 years diagnosed as having lymphoma or T-cell acute lymphoblastic leukemia who presented with superior vena cava syndrome during an 11-year period. INTERVENTIONS: Lymph node biopsy (two patients), thoracenthesis (five patients), bone marrow aspiration (two patients), and thoracenthesis in addition to bone marrow aspiration (two patients). All aspirates were evaluated with immunohistochemical studies. Chemotherapy was the only management intervention. RESULTS: T-cell lymphoma or leukemia accounted for nine cases and Hodgkin's disease for two cases. Respiratory symptoms occurred in 10 patients, including tracheal compression in six patients (compression was life-threatening in one patient). Diagnosis of superior vena cava syndrome was achieved in eight patients using surface-marker analysis of aspirates. The syndrome disappeared within 2 to 10 days. Seven of nine children whose conditions were diagnosed more than 1 year before this writing were alive and free of disease after mean follow-up of 37 months. CONCLUSIONS: (1) A specific diagnosis can be achieved in most children with superior vena cava syndrome and lymphoma; (2) Thoracic computed tomographic scans are essential, identifying minute pleural effusions that can aid diagnosis; (3) Anesthetic hazard is related only to severe tracheal compression; (4) Chemotherapy achieves excellent symptomatic relief; and (5) Long-term survival, without disease, is achievable.

Child

The management of pediatric brain tumors in a tertiary center.

Between January 1982 and January 1990, 120 newly diagnosed pediatric patients were treated at The Chaim Sheba Medical Center. Sixty three (52.5%) tumors arose in the posterior fossa and 57 (47.5%) appeared supratentorially. A wide variety of histologic subtypes was seen, each requiring tumor-specific treatment. The modern imaging techniques-CT and MRI-offered better planning of operation, treatment and follow up. All children with highly malignant tumors were treated with combination chemotherapy besides the 'conventional radiotherapy'. Since 1987 the "eight in one day" protocol has been used extensively pre- and post-irradiation. Five-year survival, varied significantly according to tumor type, location and stage. The average delay from presentation of symptoms to diagnosis was 6 months. A multidisciplinary approach has been used in the treatment, rehabilitation and follow-up of these children. In this study, the results of treatment are presented and the role of chemotherapy is discussed.

Adolescent

Detection of adeno-associated virus type 2 in human peripheral blood cells.

The non-pathogenic human parvovirus, adeno-associated virus (AAV) is helper virus-dependent. However, it integrates into the cellular genome in the absence of its helper viruses. Therefore it could become a useful vector for gene therapy. Previous studies and our own results have shown that 40 to 80% of adults are seropositive for AAV and that seroconversion occurs during the first few years of life, but little is known about the route of natural infection with the virus. We used the polymerase chain reaction to detect the AAV-2 genome and identify AAV sequences within peripheral blood leukocytes (PBLs). We could detect AAV in PBLs of two of 55 healthy blood donors, and two of 16 haemophilic patients. AAV DNA replication and viral protein production in PBLs propagated in tissue culture were also examined. AAV DNA replicated very efficiently in the presence of helper adenovirus, but capsid proteins were produced at a lower level and the yield of infectious virus was very low. Our findings prove that in vivo infection of PBLs occurs, and that PBLs could mediate the spread of AAV infection to different body tissues.

Capsid

Structural organization of the murine c-kit proto-oncogene.

The murine Kit receptor gene on chromosome 5 has been found to be frequently involved in germline mutations and rearrangements, leading to a characteristic set of severe developmental defects, known as the W phenotype. Here we describe the structure of the murine c-kit gene, based on restriction analysis of genomic phage clones and sequence determination of exon-intron boundaries. The Kit-coding region is distributed over 21 exons, most of which have sizes that range between 100 and 200 base pairs. The 3' non-translated sequence and the 3' end of the coding region form a single large exon, which encompasses 2.3 kb and is flanked by polyadenylation signals. The entire region spans a genomic distance of at least 70 kb. Though the exonic demarcations of c-kit show remarkable similarity to those of the human c-fms gene (which encodes the highly related colony-stimulating factor 1 receptor), no correlation could be found between the sizes of introns that separate homologous exon pairs. The data suggest that evolutionary pressures were confined to the conservation of structures of coding exons, whereas flanking regions were subject to large changes, owing to insertions and deletions. Finally, the analysis of the Kit genomic structure reveals that the inherited mutations of the Kit gene that have been reported thus far occur at various dispersed positions within the gene. Hence, the entire gene appears to have as yet unknown features which cause it to be frequently subject to mutations in murine germline tissues.

Amino Acid Sequence

Interaction of peanut agglutinin with normal human lymphocytes and with leukemic cells.

The interaction of peanut agglutinin (PNA) with human thymocytes, peripheral blood lymphocytes, and peripheral blood cells of various types of leukemia was investigated by using fluorescein isothiocyanate-conjugated PNA. The majority of human thymocytes (60-80%) bind the lectin. The major subpopulation of thymocytes that is PNA-positive was separated from the PNA-negative cells by differential agglutination with the lectin. The two thymocyte subpopulations were tested in the mixed lymphocyte reaction and with the phytohemagglutinin of Phaseolus vulgaris. The poor response of the PNA-positive thymocytes to these stimuli indicates that these thymocytes are functionally immature. The fluorescein isothiocyanate-PNA-binding test with peripheral blood lymphocytes of leukemic patients revealed that in most acute leukemias the PNA receptor is exposed on the blastic cells, whereas in most cases of chronic leukemia the peripheral blood lymphocytes are PNA-negative. The validity of PNA as a marker of immature blood cells and its potential clinical application are discussed.

Arachis

Ferritin deposits in peripheral blood lymphocytes of Hodgkin's disease patients.

In view of the reported associations of Hodgkin's disease and ferritin, an electron microscopic study of the peripheral blood lymphocytes of these patients was done. In 5 out of the 6 patients studied intracellular ferritin deposits were seen. No such deposits were seen in the lymphocytes of healthy subjects or in those of a patient with beta-thalassemia. The lymphocyte ferritin accumulation in Hodgkin's disease can arise either from increased synthesis or from phagocytosis.

Ferritins

Adenosine deaminase activity of normal lymphocytes and leukemic cells.

Adenosine deaminase (ADA) activity was determined in peripheral blood T cells, thymocytes and blasts of 42 acute leukemia patients. Thymocytes had higher ADA activity than mature peripheral blood T cells. B ALL (acute lymphoblastic leukemia) cells had significantly lower activity compared with T ALL and non-B, non-T cells. The latter had a wide range of enzymatic activities but mostly in the T cell range. Based on these results, as well as on assays of B and T cell lines, it seems that thymus-derived cells--and especially prethymic and immature T cells--have high ADA activity. This finding could be useful in subtyping the heterogeneous group of non-B, non-T ALL.

Adenosine Deaminase

Role of radiotherapy and chemotherapy in the treatment of lymphomas.

The recent developments and results of treatment in Hodgkin's disease suggest that staging laparotomy is indicated in certain selected groups of patients and should not be performed routinely in patients whose therapy is unlikely to be changed by the findings.Early stage nodal Hodgkin's disease is best treated by extended radiotherapy. The exact role of adjuvant chemotherapy is not settled, but there are certain groups of high-risk patients who should receive chemotherapy, such as those with extensive mediastinal disease or advanced IIIA patients. In the advanced stages, chemotherapy assumes the primary role and with the MOPP programme (chlormethine, vincristine, procarbazine, and prednisone), alone or alternating with ABVD (doxorubicin, bleomycin, vinblastine, and imidazole carboxamide), a substantial number of patients can be controlled or cured.The therapeutic approach to non-Hodgkin's lymphoma should be guided mainly by the histological findings, favourable or unfavourable, and to a lesser degree also by the stage of the disease. In these patients, chemotherapy rather than radiotherapy is the treatment of choice. In the favourable histology group, a conservative approach is usually justified in the majority of patients, while in the unfavourable histology group, aggressive combination chemotherapy containing adriamycin is the recommended therapy.In underprivileged populations, the abdominal and intestinal localization of lymphomas is more common than in Europe and North America. Two lymphomas of special interest are Burkitt's lymphoma and intestinal lymphoma in their varying aspects. In both diseases, the importance of environmental factors is highly suggestive. Referral of such patients to centres involved in the management of these diseases is essential.

Antineoplastic Agents

The in vitro effect of thymic humoral factor and levamisole on peripheral blood lymphocytes in systemic lupus erythematosus patients.

The in vitro effect of thymic humoral factor (THF) and levamisole on E rosette-forming cells in the peripheral blood of seventeen patients with systemic lupus erythematosus (SLE) was studied. Patients with active disease showed a low number of E rosette-forming cells. A significant rise in the number of E rosettes was obtained after incubation with both THF and levamisole. No such effect was observed on lymphocytes from patients with inactive disease and normal controls. In seven patients, three with active disease and four with well-controlled disease, short-term cultures were performed. The effect of THF on E rosettes was found to be the same before and after the short-term cultures. Possible mechanisms, by which THF (on the one hand) and levamisole (on the other) may increase the number of E rosettes in vitro, are discussed.

Adult

The relation between therapy and herpes zoster in Hodgkin's disease.

The rate of occurrence of herpes zoster (HZ) was analyzed by the life table method in 108 Hodgkin's disease (HD) patients, diagnosed and treated during the years 1969 to 1976. Three groups, divided according to the degree of severity of the disease, were compared. The cumulative rate of occurrence of HZ at the end of the third year after diagnosis was higher in the group with intermediately extensive disease than in that with the most extensive disease (35 vs. 23%), but the difference was not significant. At the end of the fifth year, the rate was almost identical in both groups (35.3 and 35.6%, respectively). The group with the least severe form of HD had a very low HZ rate (2.2%), which was significantly different from the other two groups and close to the rate reported for normal populations. The five-year mortality rate was 0.0, 20.3 and 40.6%, respectively, in the three groups. These findings were interpreted to mean that in more advanced stages of HD, therapy and not the severity of the disease is the main factor determining the incidence of HZ. Extended field irradiation followed by a few courses of combined chemotherapy appear to have an effect similar to that of prolonged chemotherapy.

Adolescent

Hodgkin's disease of the lung.

The clinical and radiological findings in 16 patients with Hodgkin's disease involving the lung are reviewed. Lung involvement was evident at initial presentation in 11 patients and appeared during the course of the disease in five patients. All the patients had hilar as well as mediastinal lymphadenopathy; most of them--14 of 16--had the nodular sclerosis type of the disease. Patients with these combined findings are apparently more likely to develop lung lesions. Seven of the 11 patients with lung involvement at presentation were symptomatic and received combined chemotherapy in addition to radiotherapy. The lung lesions responded completely in 10 of the 11 patients, and in one they cleared slowly after more than a year of treatment. The question remains open as to whether an asymptomatic patient in the high-risk group, as described above, should receive either adjuvant chemotherapy or radiation therapy to the lung on the prophylactic basis. Our own policy is to add chemotherapy as an adjuvant to female patients and to males who have children.

Adult

Selective splenectomy in Hodgkin's disease, stages I and II. Results of treatment.

Sixty-three patients with Hodgkin's disease, in stages I or II, asymptomatic (A) or symptomatic (B), were diagnosed and followed at the Chaim Sheba Medical Center from 1969 to 1976. Only 14 were staged pathologically. Until 1971, the patients received mantle or "inverted Y" therapy only; thereafter, an extended field that included mantle, upper abdomen and spleen irradiation was given. Symptomatic patients, as well as patients with extranodal involvement, received MOPP chemotherapy (nitrogen mustard, vincristine, procarbazine and prednisone) after termination of radiotherapy. Of 51 patients who were in stage IA or IIA, six relapsed 20 to 43 months after irradiation. Three had a pelvic recurrence; two of them were surgically staged. Thus, in only 1 of 51 patients could staging laparotomy possibly have detected pelvic disease and resulted in different therapy. Our results suggest that total nodal irradiation and staging laparotomy are not mandatory in stages IA and IIA of Hodgkin's disease. The group of 12 symptomatic patients is too small to allow us to draw definite conclusions as to the role of staging laparotomy and adjuvant chemotherapy. However, in view of the high relapse rate in the upstaged symptomatic patients, it seems that chemotherapy should be given to these patients.

Adolescent