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F Bosch

Publications and source records attributed to F Bosch.

At least 73 records · Page 4Linked to original sources
PubMed1998

Expression of the adhesion molecule ICAM-1 in non-Hodgkin's lymphoma: relationship with tumor dissemination and prognostic importance.

PURPOSE: To study the expression of intercellular adhesion molecule-1 (ICAM-1) by non-Hodgkin's lymphomas and to assess its correlation with disease extension and prognosis. PATIENTS AND METHODS: ICAM-1 (CD54-IOL54) expression was studied in 70 patients (35 male/35 female; median age, 56 years) with non-Hodgkin's lymphoma from a single institution. Immunostaining was performed using a streptavidine-biotin alkaline phosphatase method and ICAM-1 expression was evaluated in a semiquantitative manner. The histologic distribution of the cases was the following: small lymphocytic, five cases; follicular, 14; mantle cell, five; diffuse large cell, 41; and T lymphoblastic, five. Forty patients (57%) were in stage IV, bulky disease was observed in 25 patients (36%), and extranodal involvement in 48 patients (69%). RESULTS: ICAM-1 expression was negative (-) in 14 patients (20%), weak (+) in 21 (30%), positive (++) in 30 (43%), and strongly positive ( ) in five (7%). No significant relationship was found between ICAM-1 expression and the lymphoma histologic subtype. Patients with negative or weak ICAM-1 expression had more frequently disseminated (stage IV) disease (74% v 40%; P = .007), extranodal involvement (86% v 51%; P = .004), and bone marrow infiltration (57% v 26%; P = .015) than the remainders. Positive ICAM-1 patients had survival rates significantly better than those in whom ICAM-1 was negative or weakly expressed [2-year overall survival: 77% v 50%, respectively; P < .025]. In a multivariate study, ICAM-1 (P = .005) maintained, along with histologic subtype (P = .001) and the international prognostic index (IPI) (P = .056), its importance for predicting survival. Finally, when the group of aggressive non-Hodgkin's lymphoma patients was analyzed, ICAM-1 expression inversely correlated with advanced stage (P = .025), extranodal involvement (P = .01), and bone marrow infiltration (P = .01), complete response (CR) achievement (65% v 32%; P = .025), and overall survival (70% v 26% at 2 years; P < .005). CONCLUSION: In lymphoma patients, ICAM-1 expression correlates with lymphoma dissemination and is useful to assess prognosis.

Adolescent↗
PubMed1998

Pyoderma gangrenosum triggered by alpha2b-interferon in a patient with chronic granulocytic leukemia.

Pyoderma gangrenosum is a neutrophilic dermatosis that is frequently associated with malignancies such as myeloproliferative disorders. The development of this dermatologic disorder is thought to be mediated by immunological mechanisms. A case of pyoderma gangrenosum associated with the administration of alpha2b-interferon (alpha2b-IFN) in a patient with chronic granulocytic leukemia is described. Discontinuation of alpha2b-IFN and the administration of cyclosporin A and prednisone resulted in cure of the pyoderma gangrenosum. Serum levels of tumor necrosis factor, interleukin-6 and soluble interleukin-2 receptor increased when the cutaneous lesions appeared and returned to normal levels when the lesion healed. We believe that this is the first reported case of pyoderma gangrenosum associated with alpha2b-IFN therapy.

Antineoplastic Agents↗
PubMed1998

Transient pancytopenia after non-A non-B non-C acute hepatitis preceding acute lymphoblastic leukemia.

Transient pancytopenia preceding childhood acute lymphoblastic leukemia (ALL) is an unfrequent but well-known event. The association of this preleukemic syndrome with hepatitis is extremely rare, with only two such cases having been published in the literature. We report the case of a 16-year-old boy who was diagnosed with B-cell type ALL that was preceded by transient pancytopenia with absent hemopoietic cells in the bone marrow following a seronegative hepatitis episode. The clinical, morphologic and immunophenotypic features of this patient are described and the literature on this preleukemic syndrome reviewed, with special emphasis being made on its differential diagnosis with hepatitis-associated aplastic anemia.

Adolescent↗
PubMed1997

Regulated production of mature insulin by non-beta-cells.

Rat hepatoma cells were engineered to express, in a regulated manner, mature human insulin as an approach to the development of artificial beta-cells for insulin-dependent diabetes mellitus (IDDM) gene therapy. A chimeric gene obtained by linking a 2.4-kb fragment of the P-enolpyruvate carboxykinase (PEPCK) gene promoter to a human proinsulin gene (PEPCK/Insm), containing genetically engineered furin endoprotease cleavage sites, was stably transfected into FTO-2B rat hepatoma cells. The FTOInsm cells expressed high levels of insulin mRNA and protein after Northern blot or immunocytochemical analysis. High-performance liquid chromatography (HPLC) fractionation of culture medium and cell extracts revealed that about 90% of the proinsulin was processed to mature insulin. Insulin secretion was very fast, and 15 min after induction with dibutyryl cyclic AMP (Bt2cAMP) plus dexamethasone significant amounts of the hormone were released. Moreover, during the first hour, the rise in insulin concentration in the medium was 10-fold that detected in nontreated FTOInsm cells. Insulin produced by FTOInsm cells was biologically active because it blocked endogenous PEPCK gene expression and induced glucose uptake and lactate production. Thus, our results showed that genetically engineered FTOInsm hepatoma cells synthesized, processed, and secreted active insulin. The implantation of encapsulated engineered FTOInsm cells might provide a safe and practical therapeutic approach for IDDM treatment.

Animals↗
PubMed1997

Chronic lymphocytic leukemia: a changing natural history?

There are some data suggesting that the natural history of chronic lymphocytic leukemia (CLL) may be changing, but a systematic analysis of this topic is lacking. To address this issue, we examined two cohorts of CLL patients in whom the diagnosis was established in 1960-1979 (group I) and in 1980-1989 (group II), respectively. Striking differences were observed between both cohorts. The diagnosis in the second group was established at higher age (65.8 vs 61.3 years; P = 0.0001), both in males (63.8 vs 59.1 years; P = 0.004) and females (68.3 vs 64.2 years; P = 0.01); the proportion of patients in whom the diagnosis was established in low-risk clinical stage (Binet's A) was significantly higher in group II (65.7% vs 42.6%; P < 0.001), and the survival was more than double in group II (median of 11.1 vs 5.3 years; P < 0.0001). Moreover, the impact of the disease on life expectancy was much lower in the more recent cohort. These differences may be due, at least in part, to changes in the natural history of the disease.

Age Factors↗
PubMed1997

B-cell chronic lymphocytic leukemia: recent progress in biology, diagnosis, and therapy.

B-cell chronic lymphocytic leukemia (CLL) is a highly common form of leukemia characterized by the accumulation of long-lived, functionally inactive, mature appearing neoplastic B lymphocytes. In addition, immune disturbances such as hypogammaglobulinemia and autoimmune phenomena (particularly, autoimmune hemolytic anemia) are frequently found in CLL patients [1-2]. The etiology of CLL is unknown. In contrast with other leukemias, there is no relationship between CLL and exposure to radiation or other cytotoxic agents. A genetic basis is highly likely since there are differences in the incidence of CLL in different countries (e.g., CLL accounts for 30%-40% of all the leukemias in Western countries as compared to 5%-10% in Asian countries) and the risk of contracting CLL is higher among persons with first-degree relatives with the disease [3]. Because the incidence of CLL increases with age and the longer life expectancy of the general population, the age of patients at diagnosis is increasing. The median age at diagnosis is now about 70 years, with only one-third of the patients being less than 60 years of age. In the majority of the series, males predominate over females in a proportion of 1.5/1. The prognosis of patients with CLL is variable. However, clinical stages and other prognostic factors allow the individual risk of each patient to be assessed very accurately, which is useful for making treatment decisions. In the past two decades, significant progress has been made in CLL [4-10]. This review summarizes recent advances in the biology, diagnosis, and therapy of CLL.

Humans↗
PubMed1997

Treatment of B-cell chronic lymphocytic leukaemia: current status and future perspectives.

In the last two decades, important advances have been made in the biology, natural history, and prognosis of B-cell chronic lymphocytic leukaemia (CLL). In addition, treatment possibilities for patients with CLL have changed as a result of the identification of prognostic factors for survival and the availability of new drugs and treatment strategies. Patients in the early clinical stages (Binet A, Rai 0) with stable disease have a probability of long survival and should not be treated unless the disease progresses. In contrast, most patients with poor prognostic features, such as an advanced clinical stage (Binet B, C; Rai III, IV), diffuse bone-marrow infiltration or rapidly increasing blood lymphocyte levels, have a median survival probability of < 5 years and require therapy. Purine analogues are highly effective. Among these, fludarabine has become the treatment of choice for patients failing standard therapies. The role of purine analogues either alone or in combination with other drugs as front-line therapy is being investigated. Certain situations (e.g. autoimmune cytopenias, hypersplenism) require special treatment approaches (e.g. corticosteroids, splenectomy). Transplants of progenitor haematopoietic cells are also increasingly performed and deserve further investigation in younger patients with poor prognostic features. As a result of these advances, symptoms palliation is no longer the only possible goal in CLL therapy; sustained remissions and even cures are likely to be obtained in the near future.

Chronic Disease↗
PubMed1996

Correction of diabetic alterations by glucokinase.

Hyperglycemia is a common feature of diabetes mellitus. It results from a decrease in glucose utilization by the liver and peripheral tissues and an increase in hepatic glucose production. Glucose phosphorylation by glucokinase is an initial event in glucose metabolism by the liver. However, glucokinase gene expression is very low in diabetic animals. Transgenic mice expressing the P-enolpyruvate carboxykinase/glucokinase chimeric gene were generated to study whether the return of the expression of glucokinase in the liver of diabetic mice might prevent metabolic alterations. In contrast to nontransgenic mice treated with streptozotocin, mice with the transgene previously treated with streptozotocin showed high levels of both glucokinase mRNA and its enzyme activity in the liver, which were associated with an increase in intracellular levels of glucose 6-phosphate and glycogen. The liver of these mice also showed an increase in pyruvate kinase activity and lactate production. Furthermore, normalization of both the expression of genes involved in gluconeogenesis and ketogenesis in the liver and the production of glucose and ketone body by hepatocytes in primary culture were observed in streptozotocin-treated transgenic mice. Thus, glycolysis was induced while gluconeogenesis and ketogenesis were blocked in the liver of diabetic mice expressing glucokinase. This was associated with normalization of blood glucose, ketone bodies, triglycerides, and free fatty acids even in the absence of insulin. These results suggest that the expression of glucokinase during diabetes might be a new approach to the normalization of hyperglycemia.

Animals↗
PubMed1996

[Treatment with fludarabine of lymphoid neoplasms with low grade malignity resistant to treatment or in relapse].

BACKGROUND: In the last years the treatment of patients with chronic lymphocytic leukemia (CLL) and low-grade lymphomas (NHL) has changed because of the introduction of new agents, mainly the purine analogs. We report our experience with fludarabine in patients with indolent lymphoid malignancies that were previously treated with conventional agents. PATIENTS AND METHODS: Twenty patients were studied. Eleven had CLL and nine NHL. Among the patients with CLL and NHL, 72 and 100%, respectively, had advanced disease. All patients had previously been treated. Fludarabine was administered by intravenous infusion at a dose of 25 mg/m2, for 5 days every 4 weeks until a maximum of 6 cycles. RESULTS: Neither complete response (CR) nor partial response (PR) was recorded in patients with CLL; 4 (36%) achieved clinical improvement. Among the 9 patients with NHL, 3 (33%) had a CR and one a PR; two of the 3 patients with CR also achieved a molecular remission. In 3 patients with CLL their disease progressed from stage II to IV. Three patients (one with CLL and two with NHL) developed high-grade lymphoma during or immediately after the treatment with fludarabine. The major toxicities were infections: 3 patients had lobar pneumonia and one an interstitial pneumonia without microbiological identification. CONCLUSIONS: Fludarabine is an active agent in patients with low-grade lymphoid malignancies refractory to the treatment or in relapse. The possibility of obtaining molecular remissions makes this agent specially interesting in those therapies including hemopoietic progenitors transplantation as intensification treatment.

Adult↗
PubMed1996

p53 gene mutations and protein overexpression are associated with aggressive variants of mantle cell lymphomas.

Mantle cell lymphoma (MCL) is molecularly characterized by bcl-1 rearrangement and cyclin D1/PRAD-1 gene overexpression. Some aggressive variants have been recognized with a blastic or large cell morphology, higher proliferative activity, and shorter survival. p53 gene mutations in lymphoid neoplasms have been detected mainly in high grade lymphomas and have been associated with tumor progression in follicular and small lymphocytic lymphomas. To determine the role of p53 alterations in MCL, we examined 35 typical and 8 aggressive variants (5 blastic and 3 large cell) of MCLs by a combination of immunohistochemistry, single-strand conformational polymorphism analysis of genomic DNA and/or cDNA obtained by reverse transcriptase-polymerase chain reaction, denaturing gradient gel electrophoresis, and sequencing. Of the 8 aggressive MCLs, 3 (38%) contained missense point mutations in axon 8 codon 278 (Pro --> Leu), exon 8 codon 273 Arg --> His), and exon 5 codon 151 (Pro --> Ser), respectively. A diffuse p53 protein overexpression was observed in more than 50% of the tumor cells in these 3 cases. A fourth blastic MCL also showed strong p53 immunoreactivity. However, no mutations were detected in exons 5-9 in this case. p53 expression was also detected in 10% of the cells in an additional large cell type of MCL and in less than 1% of the cells in 6 typical cases. No mutations were detected in any of these cases or in the remaining cases with no expression of the protein. Four nucleotide changes were observed by single-strand conformational polymorphism analysis in 4 typical MCLs with no overexpression of the protein. Direct sequencing showed that these nucleotide changes were located at exon 6 (1 case), intron 7 (2 cases), and intron 8 (1 case). The changes in exon 6 and intron 7 were known polymorphisms. The nucleotide change in intron 8 was outside splicing sites of the neighboring exons. The overall survival of the 3 patients with p53 mutations (median, 18.3 months) was significantly shorter than that of patients with the nonmutated MCLs (median, 49 months; P < .01). These findings indicate that p53 gene mutations are an infrequent phenomenon in MCLs and are associated with a subset of aggressive variants.

Base Sequence↗
PubMed1996

Tissue-specific expression and dietary regulation of chimeric mitochondrial 3-hydroxy-3-methylglutaryl coenzyme A synthase/human growth hormone gene in transgenic mice.

We have studied the role of the mitochondrial 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) synthase gene in regulating ketogenesis. The gene exhibits expression in various tissues and it is regulated in a tissue-specific manner. To investigate the underlying mechanisms of this expression, we linked a 1148-base-pair portion of the mitochondrial HMG-CoA synthase promoter to the human growth hormone (hGH) gene and analyzed the expression of the hGH reporter gene in transgenic mice. mRNA levels of hGH were observed in liver, testis, ovary, stomach, colon, cecum, brown adipose tissue, spleen, adrenal glands, and mammary glands from adult mice, and also in liver and stomach, duodenum, jejunum, brown adipose tissue, and heart of suckling mice. There was no expression either in kidney or in any other nonketogenic tissue. The comparison between these data and those of the endogenous mitochondrial HMG-CoA synthase gene suggests that the 1148 base pairs of the promoter contain the elements necessary for expression in liver and testis, but an enhancer is necessary for full expression in intestine of suckling animals and that a silencer prevents expression in stomach, brown adipose tissue, spleen, adrenal glands, and mammary glands in wild type adult mice. In starvation, transgenic mice showed higher expression in liver than did wild type. Both refeeding and insulin injection reduced the expression. Fat diets, composed in each case of different fatty acids, produced similar expression levels, respectively, to those found in wild type animals, suggesting that long-, medium-, and short-chain fatty acids may exert a positive influence on the transcription rate in this 1148-base-pair portion of the promoter. The ketogenic capacity of liver and the blood ketone body levels were equal in transgenic mice and in nontransgenic mice.

Animals↗
PubMed1996

Prevention of diabetic alterations in transgenic mice overexpressing Myc in the liver.

Recent studies have demonstrated that the overexpression of the c-myc gene in the liver of transgenic mice leads to an increase in both utilization and accumulation of glucose in the liver, suggesting that c-Myc transcription factor is involved in the control of liver carbohydrate metabolism in vivo. To determine whether the increase in c-Myc might control glucose homeostasis, an intraperitoneal glucose tolerance test was performed. Transgenic mice showed lower levels of blood glucose than control animals, indicating that the overexpression of c-Myc led to an increase of blood glucose disposal by the liver. Thus, the increase in c-Myc might counteract diabetic hyperglycemia. In contrast to control mice, transgenic mice treated with streptozotocin showed normalization of concentrations of blood glucose, ketone bodies, triacylglycerols and free fatty acids in the absence of insulin. These findings resulted from the normalization of liver metabolism in these animals. While low glucokinase activity was detected in the liver of diabetic control mice, high levels of both glucokinase mRNA and enzyme activity were noted in the liver of streptozotocin-treated transgenic mice, which led to an increase in intracellular levels of glucose 6-phosphate and glycogen. The liver of these mice also showed an increase in pyruvate kinase activity and lactate production. Furthermore, normalization of both the expression of genes involved in the control of gluconeogenesis and ketogenesis and the production of glucose and ketone bodies was observed in streptozotocin-treated transgenic mice. Thus, these results suggested that c-Myc counteracted diabetic alterations through its ability to induce hepatic glucose uptake and utilization and to block the activation of gluconeogenesis and ketogenesis.

Animals↗
PubMed1996

[Alpha interferon treatment in idiopathic hypereosinophilic syndrome resistant to conventional therapy].

The idiopathic hypereosinophilic syndrome (HES) is an infrequent entity defined by an eosinophil count > 1.5 x 10(9)/l and the specific infiltration of different organs not attributable to another disease. Its prognosis is marked by the complications derived from visceral, particularly cardiac, infiltration determining a median survival of less than one year if treatment is not administered. Although a notable prolongation in survival may be achieved in these patients with the administration of glucocorticoids and cytolytic drugs, mainly hydroxiurea, there remains a group of patients who do not respond to these therapeutic measures, thus leading to alpha interferon trials with promising results. A favourable experience with the use of alpha interferon in two patients with IHS resistant to conventional treatment is reported. The first patient presented a picture characterized by diarrhoea, palpitations and effort dyspnea demonstrating heart involvement suggestive of eosinophilic infiltration on echocardiographic study. The second patient presented dyspneic night cough and generalized pruritus in addition to anemia and thrombocytopenia. The administration of alpha interferon (3 x 10(6) U/3 days a week and 3 x 10(6) U/day, respectively) was followed in both cases by the rapid disappearance of the symptomatology, normalization of the hematologic parameters and a reduction of the eosinophilia to values of less than 1 x 10(9)/l. This response has maintained over the two years of control in which the patients have received alpha interferon as a maintenance treatment.

Adult↗
PubMed1996

Bone marrow assessment in B-cell chronic lymphocytic leukaemia: aspirate or biopsy? A comparative study in 258 patients.

To evaluate the relative merits and prognostic value of bone marrow aspirate and bone marrow biopsy in the assessment of bone marrow infiltration in B-cell chronic lymphocytic leukaemia (CLL), two observers independently reviewed the percentage of lymphocytes in bone marrow aspirate (lymphocytic infiltration, LI) and the bone marrow histological pattern (BMP) in 258 patients. The inter-observer reproducibility and agreement was higher for BMP than for LI. BMP was an independent prognostic factor for survival in the whole series, whereas LI only had independent predictive value in stage A patients. In the entire series, disease progression was predicted by either BMP and LI, whereas in stage A patients only by BMP. Regarding low-risk CLL (smouldering CLL or A"1 substage), BMP led to a more reproducible identification of these clinical forms than LI. In conclusion, although both BMP and LI are of value to estimate bone marrow infiltration in CLL and to predict the outcome of the disease, BMP is more reliable and reproducible than LI.

Aged↗