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Biomedical subjects

F Bosch

Publications and source records attributed to F Bosch.

At least 37 records · Page 2Linked to original sources
PubMed2000

Transgenic mice overexpressing insulin-like growth factor-II in beta cells develop type 2 diabetes.

During embryonic development, insulin-like growth factor-II (IGF-II) participates in the regulation of islet growth and differentiation. We generated transgenic mice (C57BL6/SJL) expressing IGF-II in beta cells under control of the rat Insulin I promoter in order to study the role of islet hyperplasia and hyperinsulinemia in the development of type 2 diabetes. In contrast to islets from control mice, islets from transgenic mice displayed high levels of IGF-II mRNA and protein. Pancreases from transgenic mice showed an increase in beta-cell mass (about 3-fold) and in insulin mRNA levels. However, the organization of cells within transgenic islets was disrupted, with glucagon-producing cells randomly distributed throughout the core. We also observed enhanced glucose-stimulated insulin secretion and glucose utilization in islets from transgenic mice. These mice displayed hyperinsulinemia, mild hyperglycemia, and altered glucose and insulin tolerance tests, and about 30% of these animals developed overt diabetes when fed a high-fat diet. Furthermore, transgenic mice obtained from the N1 backcross to C57KsJ mice showed high islet hyperplasia and insulin resistance, but they also developed fatty liver and obesity. These results indicate that local overexpression of IGF-II in islets might lead to type 2 diabetes and that islet hyperplasia and hypersecretion of insulin might occur early in the pathogenesis of this disease.

Animals↗
PubMed1999

Increased number of chromosomal imbalances and high-level DNA amplifications in mantle cell lymphoma are associated with blastoid variants.

Mantle cell lymphomas (MCLs) are characterized by 11q13 chromosomal translocations and cyclin D1 overexpression. The secondary genetic and molecular events involved in the progression of these tumors are not well known. In this study, we have analyzed 45 MCLs (32 typical and 13 blastoid variants) by comparative genomic hybridization (CGH). To identify the possible genes included in the abnormal chromosome regions, selected cases were analyzed for P53, P16(INK4a), RB, C-MYC, N-MYC, BCL2, BCL6, CDK4, and BMI-1 gene alterations. The most frequent imbalances detected by CGH were gains of chromosomes 3q (49%), 7p (27%), 8q (22%), 12q (20%), 18q (18%), and 9q34 (16%) and losses of chromosomes 13 (44%), 6q (27%), 1p (24%), 11q14-q23 (22%), 10p14-p15 (18%), 17p (16%), and 9p (16%). High-level DNA amplifications were identified in 11 different regions of the genome, predominantly in 3q27-q29 (13%), 18q23 (9%), and Xq28 (7%). The CGH analysis allowed the identification of regional consensus areas in most of the frequently involved chromosomes. Chromosome gains (P =. 02) and losses (P =.01) and DNA amplifications (P =.015) were significantly higher in blastoid variants. The significant differences between blastoid and typical tumors were gains of 3q, 7p, and 12q, and losses of 17p. CGH losses of 17p correlated with P53 gene deletions and mutations. Similarly, gains of 12q and high-level DNA amplifications of 10p12-p13 were associated with CDK4 and BMI-1 gene amplifications, respectively. One of 2 cases with 8q24 amplification showed C-MYC amplification by Southern blot. Alterations in 2p, 3q, 13, and 18q were not associated with N-MYC, BCL6, RB, or BCL2 alterations, respectively, suggesting that other genes may be the targets of these genetic abnormalities in MCLs. Increased number of gains (0 v 1-4 v >4 gains per case) (P =.002), gains of 3q (P =.02), gains of 12q (P =.03), and losses of 9p (P =. 003) were significantly associated with a shorter survival of the patients. These results indicate that an increased number of chromosome imbalances are associated with blastoid variants of MCLs and may have prognostic significance.

Blotting, Southern↗
PubMed1999

Insulin production by engineered muscle cells.

Type 1 diabetic patients depend dramatically on insulin replacement therapy, which involves the administration of intermediate- or long-acting insulin, together with short-acting insulin to mimic physiological insulin profiles. However, the delayed-action preparations available are not generally able to produce smooth background levels of insulin. Muscle cells were tested for long-term delivery of active human insulin as an approach to achieve a constant basal level of insulin. Thus, C2C12 mouse myoblast cells were stably transfected with a chimeric gene obtained by linking the myosin-light chain 1 (MLC1) promoter to the human proinsulin gene, containing genetically engineered furin endoprotease cleavage sites (MLC1/Insm). When differentiated, C2C12Insm myotube cells expressed high levels of insulin mRNA and protein, whereas no insulin was detected in myoblast cells. HPLC fractionation of culture medium and cell extracts from differentiated C2C12Insm cells revealed that about 90% of the proinsulin was processed to mature insulin. In addition, these cells released significant levels (about 100 microU/10(6) cells/hr) of mature insulin to the medium. The hormone was biologically active since it increased glucose consumption and utilization by the differentiated C2C12Insm cells and was able to block the expression of the endogenous phosphoenolpyruvate carboxykinase (PEPCK) gene in FTO-2B rat hepatoma cells. Furthermore, when C2C12Insm myoblast cells were transplanted into diabetic mice an increase in insulinemia and a decrease in hyperglycemia were observed. Thus, our results suggest that the use of engineered myotube cells continuously secreting a defined level of insulin might be a useful approach to improve the efficacy of insulin injection treatment.

Animals↗
PubMed1999

[Non-gastric mucosa-associated lymphoid tissue (MALT) lymphomas: analysis of 14 patients].

BACKGROUND: Mucosa-associated lymphoid tissue (MALT) lymphomas are a well defined group of B-cell non-Hodgkin's lymphomas, that arise in a wide variety of extranodal sites, most frequently in the stomach and related to Helicobacter pylori infection. The aim of the present study was to analyze the presenting features, natural history and outcome in 14 patients with non-gastric MALT lymphoma. PATIENTS AND METHODS: The main clinical data, treatment and outcome were recorded for the 14 patients with non-gastric MALT lymphoma diagnosed at a single institution in a 12 year period. The median age was 68 years and 13 patients were females. Diagnosis was made according to the REAL classification criteria. RESULTS: The initial location was thyroid (3 patients), parotid (three), submaxilar gland (three), skin (two), Waldeyer's ring (one), breast (one), lung (one), small bowel (one), liver (one) and ovary (one). At diagnosis 3 patients had > or = 2 extranodal involved sites. Autoimmune disorders were present in 5 patients: Hashimoto's thyroiditis (three), Sjögren's syndrome (one) and both (one). Two patients had a poor performance status (ECOG > 1) and B-symptoms. Five patients (36%) were in stage IV, two of them because of bone marrow infiltration. All patients had a normal serum LDH level, and 5 had high beta 2-microglobulin level. The treatment consisted in surgical resection (2 patients), surgery and radiotherapy (one), surgery and chemotherapy (two), chemotherapy and radiotherapy (two) and chemotherapy alone (7 patients, three of them with doxorubicin-containing regimens). Twelve patients were evaluable for response. Complete response, partial response and failure rates were 75, 17 and 8%, respectively. Two of the 11 responders progressed, one of them with advanced stage disease. The actuarial 4-year disease-free survival was 77% (CI 95%: 47-100%). After a median follow-up of 3.4 years, 100% of the patients were alive. CONCLUSION: Non-gastric MALT lymphomas may be associated with autoimmune disorders, may present as disseminated disease and have a very good outcome.

Adult↗
PubMed1999

Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain.

Programmed cell death (apoptosis) occurs during normal development of the central nervous system. However, the mechanisms that determine which neurons will succumb to apoptosis are poorly understood. Blockade of N-methyl-D-aspartate (NMDA) glutamate receptors for only a few hours during late fetal or early neonatal life triggered widespread apoptotic neurodegeneration in the developing rat brain, suggesting that the excitatory neurotransmitter glutamate, acting at NMDA receptors, controls neuronal survival. These findings may have relevance to human neurodevelopmental disorders involving prenatal (drug-abusing mothers) or postnatal (pediatric anesthesia) exposure to drugs that block NMDA receptors.

Animals↗
PubMed1999

Expression of potentially oncogenic HHV-8 genes in an EBV-negative primary effusion lymphoma occurring in an HIV-seronegative patient.

Primary effusion lymphoma (PEL) is a novel lymphoproliferative disorder associated with human herpesvirus 8 (HHV-8) infection. Most PELs develop in HIV-seropositive individuals and are nearly always positive for Epstein-Barr virus (EBV), a finding which obscures the role of HHV-8 in lymphomagenesis. However, rare EBV-negative PEL cases occurring in HIV-seronegative patients have been reported, suggesting that HHV-8 may be pathogenetic by itself. To investigate whether HHV-8 may contribute to PEL development in the absence of EBV, the expression of seven potentially oncogenic HHV-8 open reading frames (ORFs) (ORF72/viral cyclin D, ORF16/viral bcl-2, ORF74/viral G-protein coupled receptor, ORFK2/viral IL-6, ORFK13/viral FLICE inhibitory protein, ORFK9/viral interferon regulatory factor, and ORFK1, equivalent to the gene encoding herpesvirus saimiri transforming protein) was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR) in an EBV-negative PEL presenting in an HIV-negative patient. RNA transcripts were demonstrated for the seven HHV-8 genes, and this was confirmed by hybridization to specific oligonucleotide probes. The expression of potentially oncogenic HHV-8 genes in this HIV-, EBV-negative PEL case suggests that HHV-8 may induce malignant transformation of B-lymphocytes through different molecular pathways in the absence of EBV infection.

Gene Expression↗
PubMed1999

Translocation (11;14)(q13;q32) and preferential involvement of chromosomes 1, 2, 9, 13, and 17 in mantle cell lymphoma.

We have studied 13 cases of histologically confirmed mantle cell lymphomas (MCL) combining cytological-immunological features with conventional cytogenetics and in situ hybridization (ISH) techniques. Peripheral blood smears and lymph node biopsies expressed the typical mantle zone pattern with alpha B-cell phenotype. Most of the cases (11 of 13) had lymphomatous cells in the peripheral blood. Chromosome analysis was carried out on lymphoid cells from peripheral blood and/or lymph node biopsies. Phytohemagglutinin (PHA) and phorbol 12-myristate 13 acetate (TPA) were used as mitogens. Biotin-labeled libraries of whole chromosomes implicated in complex karyotypes were used to improve their interpretation. Clonal chromosome abnormalities were found in 10 of 13 patients (77%); 7 of these had a complex abnormality. The most frequent recurrent structural abnormalities were: t(11;14)(q13;q32), involvement of chromosome 1 (der[1], del[1], dup[1]), chromosome 2 (del[2], der[2]), chromosome 9 (der[9], -9), chromosome 13 (add[13], t[13q]), and chromosome 17 (add[17], der[17], t[17q]). The most frequent numerical abnormalities were monosomy 21 and loss of the Y chromosome.

Adult↗
PubMed1999

An epidemiological comparison of pain complaints in the general population of Catalonia (Spain).

Epidemiological studies help to establish the health status in a country and allow a better allocation of economic resources. This survey estimated pain prevalence in Catalonia (Spain), analysed its relationship with demographic variables and evaluated pain-associated disabilities. The study was carried out in 1964 adults via phone interviews asking about any pain complaint they experienced in the last 6 months, regardless of its intensity and duration. Overall pain prevalence was 78.6%, significantly lower in men, with a trend to decrease with age. Back (50.9%), head (42%) and legs (36.8%) were the most affected locations. Less educated people reported, in general, higher prevalences. Pain described to be most annoying was related to musculoskeletal disease (26.2%) and migraines (16.5%). Pain was either very severe or unbearable in 33% of the sample, with women and older people reporting higher intensities. Personal and social activities were affected in 25.4% of cases and in 10.4% they became virtually impossible. Both the limitation of activity and the need for bed rest, which occurred in 19.6% of those who suffered pain, were more common amongst unemployed people, whereas 10.2% of workers had to take days off work due to pain, and 3.3% were fully incapacitated by it. In conclusion, the prevalence of pain was clearly higher among women, with an inverse relationship to age. Back pain and headaches were most prevalent and pain was rated as very severe to unbearable in one third of the patients. Pain-associated disabilities were a frequent finding. The present survey reports that pain is a substantial problem in the Catalonian population and generally reflects the characteristics of data previously reported in Anglo-saxon and Scandinavian countries.

Adult↗
PubMed1999

c-myc mRNA expression and genomic alterations in mantle cell lymphomas and other nodal non-Hodgkin's lymphomas.

Cyclin D1 is a weak oncogene that cooperates with c-myc activation in the development of B cell lymphomas in transgenic animals. Cyclin D1 is constantly overexpressed in human mantle cell lymphomas (MCL). However, the status of c-myc gene in these tumors is not known. We have examined the c-myc mRNA expression and genomic alterations, including mutational analysis of exon 1, intron 1, and exon 2 regulatory elements, in a series of 33 MCL, 22 typical and 11 blastoid variants. In addition, c-myc alterations were also examined in 56 nodal non-Hodgkin's lymphomas (NHL). c-myc mRNA overexpression was found in 38% (11/29) of MCL with a slightly higher frequency in blastoid variants (5/10, 50%) than in typical cases (6/19, 31%). Genetic alterations were only found in one blastoid MCL showing a three-fold c-myc gene amplification. In other nodal NHL, c-myc overexpression was found in 24% (7/29) of indolent tumors but in 70% (19/27) of aggressive variants. c-myc Genetic alterations detected in these cases were gene rearrangement and hypermutations in one Burkitt's lymphoma, and individual point mutations in intron 1 or exon 2 in 1/19 (5%) indolent and 7/16 (44%) aggressive variants. These results indicate that c-myc is overexpressed in a subset of MCL, but structural gene alterations are less frequent than in other nodal NHL.

Blotting, Southern↗
PubMed1999

A survey of postoperative pain treatment in children of 3-14 years.

There is a lack of information concerning the characteristics of pediatric postoperative pain in Southern European countries. The aim of this study was to document how postoperative pain in children was managed routinely at Spanish surgical wards.The study was carried out in three hospitals on the first postoperative day. Children were divided in four groups according to their age (years): Group I (3-5), II (6-8), III (9-11) and IV (12-14). The parameters evaluated were: analgesia characteristics (type of prescription, drug used and route of administration, prescribed dose and whether the drug was or was not administered, need of non-prescribed analgesics) and the postoperative pain intensity. The results were analysed using descriptive statistics. U-Mann Whitney, chi(2), ANOVA, Kruskall-Wallis and Student's t -test were also used.A total of 348 children ranging from 3 to 14 years were studied. The average age (+/- SD) was 8.2 +/- 3.3 and the majority were male (74%). Urologic surgery was the most frequent type of operation, with age (p<0.05) and hospital differences (p<0.001). The majority of the patients (52%) were prescribed an analgesic, but only 26% of them had an analgesia order at fixed dosage intervals. Differences among the hospitals were observed (p<0.001). The most commonly used analgesics were metamizol, propyphenazone, paracetamol and codeine. Differences in choice of drug in relation to age and hospital were significant (p< 0.001). Rectal was the preferred route of drug administration. Patient's age was unrelated with the prescribed analgesic dose. An average of 68% of prescriptions were given and half of the patients without scheduled analgesia needed to have analgesics administered. Around 20% of patients had high pain scores.Few paediatric patients are given analgesics at fixed dose intervals to treat postoperative pain. Pain relief therapy for children differs notably to that of adults, in respect to the drugs prescribed and the administered route. Copyright 1999 European Federation of Chapters of the International Association for the Study of Pain.

Journal Article↗
PubMed1999

Expression of beta-integrin adhesion molecules in non-Hodgkin's lymphoma: correlation with clinical and evolutive features.

PURPOSE: To analyze beta-integrin expression in non-Hodgkin's lymphomas (NHLs) in order to assess its distribution among histologic subtypes and correlate with clinical features and outcome. PATIENTS AND METHODS: The expression of alpha2 through alpha6 and beta1 common chains of very late activation antigen (VLA ) molecules and alphaL (CD11a) and beta2 common (CD18) chains of leukocyte function-associated antigen 1 molecule were studied in 137 patients with NHL. Immunostaining was performed by a streptavidin-biotin alkaline phosphatase method, and integrin expression was semiquantitatively assessed. Correlation with clinical features was analyzed in 80 patients consecutively diagnosed as having immunocytoma (five cases), follicular lymphoma (19 cases), mantle-cell lymphoma (MCL; four cases), diffuse large-cell lymphoma (DLCL; 40 cases), lymphoblastic lymphoma (LL; six cases), anaplastic Ki-1-positive lymphoma (one case), and other peripheral T-cell lymphoma (five cases). RESULTS: MCL cells did not show alpha2 and alpha6 expression, whereas most expressed weak to moderate levels of alpha3, alpha4, and alpha5. LL mostly showed alpha2 to alpha5 expression, whereas alpha6 was observed in seven of 11 cases (higher proportion than that shown in other subgroups). Alpha chains of VLA molecules were present more frequently in T-cell than in B-cell lymphomas. Patients with moderate/strong alpha4, CD11a, and beta2 common chain expression presented more frequently with advanced stage and bone marrow infiltration. Moderate/strong alpha4, alpha5, and beta1 common chain expression correlated with extranodal involvement. In the subset of B-cell DLCL patients, negative/weak expression of alpha3 and alpha4 chains was related to a higher complete response rate. Moreover, negative or weak expression of alpha2, alpha3, alpha4, and beta1( )common chain had favorable significance for overall and failure-free survivals. CONCLUSION: In NHL, beta-integrin expression is related to histologic subtype. The expression pattern of these molecules probably influences disease dissemination and patients' prognoses.

CD18 Antigens↗
PubMed1998

Renal failure in multiple myeloma: presenting features and predictors of outcome in 94 patients from a single institution.

BACKGROUND: Twenty percent of patients with multiple myeloma (MM) have renal failure. OBJECTIVE: To analyze the presenting features, the response to therapy, and the factors associated with renal function recovery and survival in 94 patients with MM and renal failure. PATIENTS AND METHODS: Medical records of patients from our institution with MM and renal failure diagnosed between January 1969 and December 1994 were reviewed. The statistical methods consisted of Kaplan-Meier survival curves, the log-rank test, logistic regression analysis, and the Cox proportional hazards model for survival analysis. RESULTS: Renal failure was observed in 94 (22.2%) of 423 patients. Patients with renal failure had more advanced disease than the others. Patients with renal failure had a lower response rate to chemotherapy than those with normal renal function (39% vs 56%; P<.001). However, when patients dying within the first 2 months of treatment were excluded, no significant differences in the response rate were found between patients with renal failure and those with normal renal function. Renal function recovery was observed in 26% of patients. Serum creatinine level (<354 micromol/L [<4 mg/dL]), serum calcium level (> or =2.88 mmol/L [> or = 11.5 mg/dL]), and amount of proteinuria (< 1 g/24 h) were associated with renal function recovery. Patients who recovered renal function had a median survival of 28 months vs 4 months for those with nonreversible renal failure (P<.001). In the multivariate analysis, only serum creatinine level (P=.003) and response to chemotherapy (P<.001) were correlated with survival. CONCLUSIONS: Renal failure was present in almost one fourth of patients with MM. Patients with reversible renal failure had longer survival than those not recovering renal function. When patients dying within the first 2 months of treatment were excluded, the response rate was not affected by renal function. Factors associated with renal function recovery were degree of renal failure, presence of hypercalcemia, and amount of proteinuria. Response to chemotherapy and severity of renal failure were the only independent factors associated with survival.

Adult↗
PubMed1998

Evidence from transgenic mice that interferon-beta may be involved in the onset of diabetes mellitus.

A number of cytokines have been shown to alter the function of pancreatic beta-cells and thus might be involved in the development of type 1 diabetes. Interferon-beta (IFN-beta) expression is induced in epithelial cells by several viruses, and it has been detected in islets of type 1 diabetic patients. Here we show that treatment of isolated mouse islets with this cytokine was able to alter insulin secretion in vitro. To study whether IFN-beta alters beta-cell function in vivo and leads to diabetes, we have developed transgenic mice (C57BL6/SJL) expressing IFN-beta in beta-cells. These mice showed functional alterations in islets and impaired glucose-stimulated insulin secretion. Transgenic animals presented mild hyperglycemia, hypoinsulinemia, hypertriglyceridemia, and altered glucose tolerance test, all features of a prediabetic state. However, they developed overt diabetes, with lymphocytic infiltration of the islets, when treated with low doses of streptozotocin, which did not induce diabetes in control mice. In addition, about 9% of the transgenic mice obtained from the N3 back-cross to outbred albino CD-1 mice spontaneously developed severe hyperglycemia and hypoinsulinemia and showed mononuclear infiltration of the islets. These results suggest that IFN-beta may be involved in the onset of type 1 diabetes when combined with either an additional factor or a susceptible genetic background.

Animals↗
PubMed1998

Mantle cell lymphoma: presenting features, response to therapy, and prognostic factors.

BACKGROUND: The goal of this study was to analyze the presenting features, natural history, and prognostic factors in 59 patients with well characterized mantle cell lymphoma (MCL). METHODS: Cases were classified as nodular or diffuse and as typical or blastic variants. Age, performance status (PS), histologic variants, mitotic index (MI), hematologic parameters, tumor extension data, and International Prognostic Index (IPI) were recorded and evaluated for prognosis. RESULTS: The median age of the patients was 63 years (range, 39-83 years), and the male to female ratio was 3:1. Fifty-three patients had typical histology (3 nodular and 50 diffuse), and 6 had the blastic variant. Approximately 95% of patients presented with advanced stage disease (Ann Arbor Stage III-IV). Leukemic expression was observed in 58%. Complete and partial response rates were 19% and 46%, respectively. Parameters associated with lower response rate were Stage IV, high/intermediate or high risk IPI, and increased lactate dehydrogenase (LDH) level. In the logistic regression analysis, high LDH level and Stage IV disease were associated independently with lower response rate. Median survival was 49 months. Parameters associated with a short survival were: poor PS, splenomegaly, B-symptoms, MI > 2.5, leukocyte count > 10 x 10(9)/L, high LDH level, blastic variant, and high/intermediate or high risk IPI. In the Cox proportional hazards regression model, only poor PS (relative risk [RR] = 3.3; P = 0.002), splenomegaly (RR = 2.8; P = 0.007), and MI > 2.5 (RR = 2.4; P = 0.012) were associated with short survival. CONCLUSIONS: In this series, patients with MCL presented with advanced stage and extranodal involvement. Only a minority of patients achieved a complete response. The median survival was 4 years, with PS, splenomegaly, and MI being the most important factors predicting survival. These results show clearly that more effective therapies for MCL are needed.

Adult↗