1/94. Protracted and variable latency of acute lymphoblastic leukemia after TEL-AML1 gene fusion in utero.We report a pair of identical twins with concordant acute lymphoblastic leukemia (ALL). Unusually, their diagnoses were spaced 9 years apart at ages 5 and 14. Leukemic cells in both twins had a TEL-AML1 rearrangement, which was characterized at the dna level by an adaptation of a long distance polymerase chain reaction (PCR) method. The genomic fusion sequence was identical in the two leukemias, indicative of a single cell origin in one fetus, in utero. At the time twin 1 was diagnosed (aged 5 years), the bone marrow of twin 2 was hematologically normal. However, retrospective scrutiny of the dna from an archived slide with clonotypic TEL-AML1 primers showed that the presumptive preleukemic clone was present and disseminated 9 years before a clinical diagnosis. These data provide novel insight into the natural history of childhood leukemia and suggest that consequent to a prenatal initiation of a leukemic clone, most probably by TEL-AML fusion itself, the latency of ALL can be both extremely variable and protracted. This, in turn, is likely to reflect the timing of critical secondary events.- - - - - - - - - - ranking = 1keywords = long (Clic here for more details about this article) |
2/94. schizophrenia - A disturbance of signal interaction between the entorhinal cortex and the dentate gyrus? The contribution of experimental dibenamine psychosis to the pathogenesis of schizophrenia: A hypothesis.In addition to the existence of complex memory (similar to the implicit nondeclarative memory of Squire), the existence of a phylogenetically old apparatus of a memory of situations (SMA) is supposed, which is to some extent comparable with the declarative memory of Squire. During actual sensory information the SMA generates a general frame and forms a general 'mark', indicating whether a given information has its origin inside or outside the body, and whether it is new or known. The procedure of this marking process can be explained as the time-depending arrest of a copy of the actual original information-transporting signal 'shower'; this copy must last until the feedback from thalamocortical centers indicates the termination of the processing of the original signal showers. The arrest of the shower copies is the performance of neuronal networks of the entorhinal cortex (EC) and the gyrus dentatus (GD). The psychopathological and biochemical analyses of experimental dibenamine psychosis show a different effect of dibenamine on the noradrenaline (NA) receptors of the EC and GD, respectively: these effects are responsible for the repeated perception cycles of a single situation. N,N-Dibencylamine blocks the postsynaptic alpha(1)-receptors of the EC without influencing the beta-receptors of the GD. Thus the interaction between EC and GD is changed: instead of new scenes, perceptions that have just been experienced get repeated presence and the quality of familiarity. The prolonged arrest of shower copies simultaneously blocks the entrance of new signal showers from the EC to the GD. No information-transporting signal showers can come in as long as the arrest lasts. In case of a disturbance in NA-dependent actions within the EC and the GD, the duration of arrest of information-transporting signal showers is shortened. Thus the formal frame of experience receives the quality of novelty instead of familiarity, and in addition the qualities of uncertainty, vagueness, and alienity. These very changes in perception and experience represent the basic disturbance of schizophrenia. All the symptoms of schizophrenia may be explained by this basic disturbance. The analysis of biochemical aspects turns attention to the energetic situation of NA and N-methyl-D-aspartate systems. These considerations suggest a genetic background of the basic disturbance of schizophrenia: transmitter effects on membranes of neurons and possibly also on glial cells, and energy supply of these effects may be predetermined genetically. It may be assumed that the compensation of such membrane-dependent disturbances will be possible within wide areas of the neural network, except for the 'bottleneck' of the overlapping region of the iso- and allocortex.- - - - - - - - - - ranking = 2keywords = long (Clic here for more details about this article) |
3/94. Homozygous deletion of the CYP21A-TNXA-RP2-C4B gene region conferring C4B deficiency associated with recurrent respiratory infections.The central class III region of the human major histocompatibility complex contains highly polymorphic genes that are associated with immune disorders and may serve as susceptibility factors for viral infections. Many HLA haplotype specific rearrangements, duplications, conversions and deletions, occur frequently in the C4 gene region. Genetic deficiencies of complement components are associated with recurrent occurrence of bacterial infections. We have studied the complement profile and the class III genes 5'-RP1-C4A-CYP21A-TNXA-RP2-C4B-CYP21B-TNXB -3' in a 4-year-old Caucasian patient. He has suffered from several pneumonias caused by respiratory viruses, eight acute otitis media, prolonged respiratory infections and urinary tract infection. complement c4 was constantly low, but the other complement components, from C1 to C9, C1INH, factor B and properdin, were within normal limits. Immunological evaluation gave normal lymphocyte numbers and functions with the exception of subnormal T cell response to pokeweed mitogen. Molecular studies of the C4 gene region in the patient revealed homozygous deletion of CYP21A-TNXA-RP2-C4B generating total deficiency of C4B and the flanking 5' region up to C4A, and in the father a missing CYP21A gene. Further investigations are needed to elucidate the relationship between C4B deficiency and susceptibility to infections.- - - - - - - - - - ranking = 1keywords = long (Clic here for more details about this article) |
4/94. Multiple basal cell carcinomas in a patient with acute myeloid leukaemia and chronic lymphocytic leukaemia.skin cancer is a well-recognized risk of prolonged immunosuppression, for example, following renal transplantation. These tumours contrast with idiopathic lesions in that squamous cell, rather than basal cell carcinomas usually predominate. We report a Caucasian female who developed multiple basal cell carcinomas following protracted cytotoxic therapy for acute myeloid leukaemia and subsequently chronic lymphocytic leukaemia. No other clinical risk factors nor relevant polymorphisms of genes encoding for detoxifying enzymes were identified. Immune suppression is a well-recognized cause of multiple skin tumours, the most striking increase usually being of squamous cell carcinomas. We believe this woman is representative of a subgroup of immunosuppressed patients who, for as yet poorly understood reasons, have a predisposition to basal cell, rather than squamous cell carcinoma accrual.- - - - - - - - - - ranking = 1keywords = long (Clic here for more details about this article) |
5/94. Scintigraphic evidence for a specific long-chain fatty acid transporting system deficit and the genetic background in a patient with hypertrophic cardiomyopathy.The mechanism of cardiac uptake of long-chain free fatty acids has not been fully determined. We encountered a hypertrophic cardiomyopathy patient who showed a lack of cardiac uptake of 2 different types of long-chain fatty acid analogues on the scintigraphic images. Flow cytometric analysis revealed no platelet or monocyte CD36 molecule expression (type I CD36 deficiency) and his CD36 gene showed homozygous mutation for 478C to T substitution, leading to an abnormal CD36 amino acid sequence. These findings strongly suggest that a specific transporting system rather than a simple diffusion is commonly involved in the cardiac uptake of long-chain free fatty acids in humans, and that the CD36 protein is the most likely candidate for the specific transporter and to explain scintigraphic defects on fatty acid imaging.- - - - - - - - - - ranking = 7keywords = long (Clic here for more details about this article) |
6/94. Absence of MHC class II gene expression in a patient with a single amino acid substitution in the class II transactivator protein CIITA.We investigated the underlying genetic defect in an immunodeficient patient who presented with recurrent bacterial infections in his late twenties and demonstrated a transcriptional defect in major histocompatibility complex (MHC) class II regulation. Transient heterokaryon analysis implicated functional loss of CIITA, the MHC class II transactivator protein, and in support of this MHC class II antigen expression was restored by stable transfection with the wild-type molecule. A single amino acid substitution, phenylalanine to serine, in the COOH-terminal portion of the CIITA sequence correlated with reduced transcription of both classical (HLA-DP, -DQ, and -DR) and nonclassical (HLA-DM and -DO) class II genes. The long survival of the patient, although remarkable, was not associated with partial CIITA function as evidenced by residual MHC class II expression. These data define at high resolution a region of CIITA that is essential for function in both professional and nonprofessional antigen presenting cells and which could potentially constitute a target for therapeutic intervention by novel factors with a propensity to downregulate MHC class II antigen expression.- - - - - - - - - - ranking = 1keywords = long (Clic here for more details about this article) |
7/94. Renal asymmetry in children with autosomal dominant polycystic kidney disease.Although for decades autosomal dominant polycystic kidney disease (ADPKD) was considered a disease of adults, our recent longitudinal studies on children from ADPKD families have shown that the disease is evident by ultrasound imaging in approximately 75% of children who are carriers of the ADPKD1 gene, the most common form of ADPKD. Here we report that, in contrast to adults, the disease appears to be unilateral initially in approximately 17% of children. Asymmetric enlargement of the kidneys is also frequently observed. This renal asymmetry can be extreme and lead to diagnostic confusion. We present 2 unusual cases of asymmetric renal involvement that we have observed during the last 10 years. The first is a 14-year-old boy who was scheduled for a nephrectomy to relieve pain and whose family requested a second opinion. The second is a 10-year-old girl who was diagnosed with ADPKD in utero by prenatal ultrasound. After birth, 1 kidney progressively developed cysts and enlarged, whereas the other had only a few tiny cysts and remained normal in size. A review of the literature shows that presentations like these often lead to a nephrectomy or surgical biopsy. A carefully obtained family history and examination of both parents with ultrasound can help to avoid unnecessary invasive procedures. If pain is a prominent symptom, it can be treated by cyst aspiration if there are only a few cysts or a single dominant cyst. The molecular mechanism for extremely asymmetric renal disease remains to be elucidated.- - - - - - - - - - ranking = 1keywords = long (Clic here for more details about this article) |
8/94. association between Takayasu's arteritis and Crohn's disease in two young women: case reports.Among 34 patients under observation, two young women, aged 23 and 24, developed Takayasu's disease (Takayasu's arteritis) associated with Crohn's disease. The typical vascular symptoms of Takayasu's arteritis developed late during a quiescent phase of Crohn's disease. We discuss the usefulness of diagnostic methods, particularly the contribution of duplex Doppler. Currently, this method appears to provide effective diagnosis of Takayasu's arteritis although clinical data, including hyposphygmy of the radial arteries and carotidynia (pain appearing along the carotid course) are still fundamental. The possible etiopathogenic relations between these two diseases and correlation of results with those in the literature are discussed (J Mal Vasc 1999; 24: 373-376).- - - - - - - - - - ranking = 1keywords = long (Clic here for more details about this article) |
9/94. Uveal melanoma in young patients.OBJECTIVE: To study the clinical profile of young patients with uveal melanoma. DESIGN: Retrospective case-control series. SETTING: Tertiary referral center. patients: Data on 63 patients aged 20 years or younger with uveal melanoma were reviewed for clinical profile and association with oculo(dermal) melanocytosis, familial uveal melanoma, dysplastic nevus syndrome, cutaneous melanoma, and other second malignant neoplasms. RESULTS: Of 8000 patients with uveal melanoma, 63 (0.8%) were found in patients who were 20 years of age or younger. The median age at diagnosis was 16 years, and the youngest patient was 3 years old. Sixty-two patients (98%) were white, and uveal melanoma was unilateral in all cases. Seven patients (11%) had oculo(dermal) melanocytosis. Two patients (3%) had dysplastic nevi syndrome, and personal history of cutaneous melanoma was observed in 1 patient (2%). No other second cancers were present in any patient. The 5- and 15-year posttreatment survival estimates were 0.95 (95% confidence interval, 0.87-1.00) and 0.77 (95% confidence interval, 0.52-1.00), respectively. CONCLUSIONS: Uveal melanoma is rare in children or teenagers. It occurs in a heterogeneous group displaying various associations, especially with oculo(dermal) melanocytosis. Oculo(dermal) melanocytosis is 9 times (95% confidence interval, 3.6-22.8) more common in young patients with uveal melanoma than in the general population with uveal melanoma. Young patients with uveal melanoma have short-term (5-year) survival better than that of adults, but the long-term (15-year) survival is similar to that of adults. Arch Ophthalmol. 2000;118:918-923- - - - - - - - - - ranking = 1keywords = long (Clic here for more details about this article) |
10/94. Prolonged survival in hereditary surfactant protein B (SP-B) deficiency associated with a novel splicing mutation.Hereditary surfactant protein B (SP-B) deficiency has been lethal in the first year of life without lung transplantation. We tested the hypothesis that SP-B gene mutations may result in milder phenotypes by investigating the mechanisms for lung disease in two children with less severe symptoms than have been previously observed in SP-B deficiency. Immunostaining patterns for pulmonary surfactant proteins were consistent with SP-B deficiency in both children. dna sequence analysis indicated that both children were homozygous for a mutation in exon 5 that created an alternative splice site. Reverse transcriptase PCR and sequence analysis confirmed use of this splice site, which resulted in a frameshift and a premature termination codon in exon 7. The predominant reverse transcriptase PCR product, however, lacked exon 7, which restored the reading frame but would not allow translation of the exons that encode mature SP-B. Western blot analysis detected reduced amounts of mature SP-B as well as an aberrant SP-B proprotein that corresponded to the size expected from translation of the abnormal transcript. We conclude that a novel splicing mutation was the cause of lung disease in these children and that hereditary SP-B deficiency can be the cause of lung disease in older children.- - - - - - - - - - ranking = 4keywords = long (Clic here for more details about this article) |
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