1/7. 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 = 1keywords = cycle (Clic here for more details about this article) |
2/7. Impaired mitochondrial pyruvate importation in a patient and a fetus at risk.The patient was the first child of healthy consanguineous parents. She presented at birth with hypotonia, mild facial dysmorphism, periventricular cysts, marked metabolic acidosis, hyperlactacidemia with normal lactate/pyruvate molar ratios, normoglycemia, and normal ammonia. Hyperlactacidemia was severe (5-14 mmol/l) and not corrected with bicarbonate, thiamine (10 mg/d), 2-chloropropionate (100 mg/kg/d) and a ketogenic diet. Pyruvate dehydrogenase (PDHC) activity was normal in lymphocytes and fibroblasts. Functional assays were performed in digitonin-permeabilized fibroblasts to measure oxidation rates from radiolabeled pyruvate and malate. The production of [14C]acetylcarnitine or [14C]citric cycle intermediates derived from [2-14C]pyruvate as well as the release of 14CO(2) from [1-14C]pyruvate was severely impaired, whereas decarboxylation of [U-14C]malate was normal. With increasing concentrations of [1-14C]pyruvate, the patient's fibroblasts behave like control fibroblasts incubated in the presence of alpha-cyano-4-hydroxycinnamate, a specific inhibitor of mitochondrial pyruvate uptake: a progressive increase in 14CO(2) production was observed, likely due to passive diffusion of [1-14C]pyruvate through the mitochondrial membranes. Our results are consistent with a defect of mitochondrial pyruvate transport in the patient. Mutational analysis was precluded as the cDNA sequence of the pyruvate carrier has not been identified as yet in any organism. An affected fetus was recognized in a subsequent dichorionic twin pregnancy using the coupled assay measuring [2-14C]pyruvate oxidation rates on digitonin-permeabilized trophoblasts. After selective feticide, the pregnancy was uncomplicated with delivery at 37w of a healthy female, who is currently 2-month old.- - - - - - - - - - ranking = 1keywords = cycle (Clic here for more details about this article) |
3/7. Acute myelofibrosis in a patient with diffuse large cell non Hodgkin's lymphoma and renal cancer.Relapse after anthracycline based combination chemotherapy is frequently seen in patients with aggressive non Hodgkin's Lymphomas (NHL), whereas complications such as secondary leukemia or solid tumor rarely occur. We report a patient with diffuse large cell (DLC) NHL and concurrent renal cancer, who developed acute myelofibrosis (AMF) later in the course of her disease. This 60-year-old female patient presented with pancytopenia and a right sided renal mass. Diagnostic work up revealed severe bone marrow infiltration by DLC NHL and renal cancer T1N0M0G2. Cytogenetic and molecular evaluation of bone marow cells showed three distinct clones, (a normal 46XX karyotype, a ringed chromosome 7 and a third clone with an enlarged chromosome 2 as well as several fragments). The patient underwent nephrectomy and eventually received 6 cycles of CHOP 14 chemotherapy. anemia persisted followed by severe granulocytopenia and thrombocytopenia 6 weeks later. Repeated bone marrow biopsy showed absence of lymphoma and/or cancer metastasis, but massive myelofibrosis with an increased number of atypical megakaryocytes. Considering the short clinical course and the absence of hepatosplenomegaly AMF was diagnosed. The concurrence of three distinctneoplasms within a short period of time as well as the complex cytogenetic aberrations found in her bone marrow cells reflect a strong individual susceptibility to malignant disease in this patient.- - - - - - - - - - ranking = 1keywords = cycle (Clic here for more details about this article) |
4/7. Familial multiple cutaneous and uterine leiomyomas associated with papillary renal cell cancer.Multiple cutaneous and uterine leiomyomas is an autosomal dominant condition that results in benign smooth muscle tumours of the skin and, in females, uterine fibroids. This syndrome overlaps with hereditary leiomyomatosis and renal cell cancer syndrome in which affected individuals may develop the rare type II papillary renal cell cancer, in addition to skin leiomyomas. Recently, heterozygous mutations in the gene encoding fumarate hydratase have been found to underlie both conditions. fumarate hydratase is an enzyme that catalyses the conversion of fumarate to malate in the Kreb's cycle and may also function as a tumour suppressor gene. We report a family with multiple leiomyomas, uterine fibroids and papillary renal cell cancer. The proband is a 77-year-old Polish woman who developed multiple cutaneous leiomyomas on her right upper arm in her thirties and subsequently underwent a hysterectomy for uterine fibroids in her forties. She has four offspring: her eldest daughter also has skin and uterine leiomyomas with a similar onset; her son has multiple skin leiomyomas and in addition was diagnosed with metastatic papillary renal cell cancer at the age of 50 years; the two youngest daughters are unaffected. dna sequencing in all the affected individuals disclosed a heterozygous G-->C substitution at nucleotide 173 of the fumarate hydratase gene, that converts an arginine residue (CGA) to proline (CCA). This missense mutation has not been reported previously and is designated R58P. Interestingly, the clinically asymptomatic 20-year-old son of the individual with renal cancer was also found to be heterozygous for R58P. It is likely that he will develop skin leiomyomas in the future but the risk of renal cancer is difficult to predict. Nevertheless, detection of this mutation has important implications for screening and genetic counselling in this and other family members.- - - - - - - - - - ranking = 1keywords = cycle (Clic here for more details about this article) |
5/7. Familial voluntary nystagmus.PURPOSE: To examine the pathological significance and familial occurrence of voluntary nystagmus. patients AND methods: We examined two families orthoptically as well as with video and search-coil techniques or electronystagmography (ENG). Three members of three generations of the first family and a 9-year-old boy from a second family not related to the first were able to generate a voluntary horizontal nystagmus. RESULTS: The characteristics of the nystagmus of our original patient, his daughter and 8-year-old grandson (1st family) were remarkably similar: duration of 2-5 seconds, amplitudes of 1-4 degrees and frequencies around 15 cycles/second. In the second family, our patient with a congenital esotropia and hyperopia was the only one of his family who could voluntarily produce a nystagmus of about 5 degrees and 10 cycles/second for maximum of 20 seconds. During prolonged reading, the same nystagmus with disturbing oscillopsia developed involuntarily and was not suppressible. We added 0.75 diopters to both lenses of his spectacles to account for the result of our cycloplegic refraction. This stopped the involuntary nystagmus during near fixation. DISCUSSION: To avoid unintentional "bouts" of voluntary nystagmus, a reduction of the convergence impulse by plus-lenses may be effective. The parameters of voluntary nystagmus can be considered family-specific.- - - - - - - - - - ranking = 2keywords = cycle (Clic here for more details about this article) |
6/7. tail stump syndrome associated with chromosomal translocation in two brothers attempting intracytoplasmic sperm injection.OBJECTIVE: To raise the possibility that a familial chromosomal translocation associated with teratozoospermia can disrupt a gene necessary for flagellum assembly. DESIGN: Case report. SETTING: University hospital. PATIENT(S): Two brothers with infertility related to anomalies of meiotic division and of the flagella assembly, presenting the same balanced 5-12 autosomal translocation. INTERVENTION(S): Several intracytoplasmic sperm injection (ICSI) cycles in our IVF department for both couples. MAIN OUTCOME MEASURE(S): Sperm analysis, karyotypes, electron microscopy, and fluorescence in situ hybridization (FISH) analysis of spermatozoa performed using probes coding for chromosomes X, Y, 13, 18, and 21. RESULT(S): In both brothers, sperm analysis indicated a tail stump syndrome. Electron microscopy analysis displayed complex abnormalities, which were probably related to meiotic errors. The FISH analysis indicated an increase of diploid germ cells. Karyotypes of both patients revealed the same balanced chromosomal t(5;12) (p15.1; q21) translocation. Results of ICSI cycles were comparable for both couples. A twin pregnancy was achieved in one of these two couples, but a spontaneous miscarriage occurred at 10 weeks of gestation. CONCLUSION(S): The flagella anomalies raise the possibility that the translocation disrupts a gene necessary for the flagellum assembly, although a mutation in a gene unrelated to the chromosome breakpoints cannot be excluded.- - - - - - - - - - ranking = 2keywords = cycle (Clic here for more details about this article) |
7/7. Genetic mechanism of leukemia predisposition in a family with 7 cases of acute myeloid leukemia.This paper describes a family in which seven members, involving three consecutive generations, suffered from acute myeloid leukemia during the past 16 years. The genetic abnormalities were vertically transmitted in a Mendelian dominant manner without sex linkage. Cytogenetic approaches, such as G-banding karyotypes, micronuclei (MN), chromosome aberrations (CA), fragile sites (Fra), cell cycle time (Tc), sister chromatid exchanges (SCE), silver-staining nucleolar organizer regions (Ag-NOR), and silver-staining acrocentric chromosome satellite association (Ag-AA), were investigated on 19 presently healthy members of the family, compared with 10 normal controls. The results showed that their G-banding chromosome karyotypes were normal, without a single similarly located fragile site being found to be carried commonly by the blood relations, although the rare fragile site frequency in the blood relations group was higher than that in the non-blood relations group or normal controls. On the other hand, SCE and Ag-NOR were lowered in the blood relations. In III-13 and IV-3 of the pedigree, in particular, the prolonged cell cycle time with distinctly abnormal SCE and Ag-NOR might predict a high risk for leukemia. Hence the follow-up of this remarkable family is being continued.- - - - - - - - - - ranking = 2keywords = cycle (Clic here for more details about this article) |