Detection of the t(14;18) chromosomal translocation by interphase cytogenetics with yeast-artificial-chromosome probes in follicular lymphoma and nonneoplastic lymphoproliferation.

PURPOSE: The aim of this study was to establish a fluorescence in situ hybridization (FISH) technique for the detection of t(14;18)(q32;q21), characteristic for follicular lymphoma (Kiel classification: centroblastic centrocytic [cb-cc] lymphoma). MATERIALS AND METHODS: After the FISH system had been established, parallel studies of lymph node biopsy specimens from 30 patients with cb-cc lymphoma and from 32 patients with nonneoplastic lymphoproliferation were performed by means of chromosome analysis, polymerase chain reaction (PCR), and FISH analysis. Two differently labeled yeast-artificial-chromosome (YAC) probes that contained the entire bcl-2 gene and the C-region of the immunoglobulin H (IgH) gene, respectively, were used to detect t(14;18) by FISH. RESULTS: The presence of the translocation is indicated by a red (Cy3)/green (fluorescien isothiocyanate [FITC]) double signal, which corresponds to the IgH/bcl-2 fusion gene, whereas in normal cells the signals are separate. Control studies showed that the double signal is visible in less than 1% of normal cells. FISH analysis was able to identify the t(14;18) in all cases of cb-cc lymphoma we studied. All bcl-2 breakpoints can be detected. Combined immunophenotyping and interphase cytogenetics demonstrated that t(14;18) was restricted to CD22+ B lymphocytes and never occurred in CD3+ T lymphocytes. In four of 32 cases of nonneoplastic lymphoproliferation, t(14;18) was also detected. CONCLUSION: FISH turned out to be the most sensitive method to detect t(14;18). Our FISH results confirm PCR data from other groups that found evidence for the presence of t(14;18) in nonneoplastic lymphoproliferation. It needs to be determined whether, in morphologically nonneoplastic processes, t(14;18) is associated with an increased risk for the development of non-Hodgkin's lymphoma.

Simultaneous presence of t(11;14) and a variant Burkitt's translocation in the terminal phase of a mantle cell lymphoma.

Little is known about the clinical significance of secondary chromosome aberrations in lymphomas with t(11;14)(q13;q32), the characteristic change of mantle cell lymphomas. Here we present a patient with mantle cell lymphoma, who showed a variant Burkitt's translocation t(2;8)(p12;q24) in addition to t(11;14) during the progression of the disease. An involvement of chromosome 8q24, the localization of the c-myc gene, has so far been described in only four patients, who seemed to have a fatal clinical course. Although no blastic transformation occurred in our patient, no remission could be induce by intensified treatment and survival was only 5 months. This case demonstrates that secondary chromosome aberrations can determine the clinical course of patients, even if morphologic and immunophenotypic findings fail to predict the poor outcome.

Luminography--an alternative assay for detection of von Willebrand factor multimers.

A luminescence assay was adapted for detection of von Willebrand factor multimers subsequent to SDS-agarose gel electrophoresis and electroblotting onto nitrocellulose. The method is as fast as chromogenic detection methods and appears to be as sensitive as autoradiography without the disadvantages of the latter.

Luminographic detection of von Willebrand factor multimers in agarose gels and on nitrocellulose membranes.

Two methods for visualization of vWf multimers were compared with respect to sensitivity and detection of normal vWf and vWd variants IIA, IIB, IIC, IID, IIE, and IIF. Autoradiography and luminography after electrotransfer of vWf multimers onto nitrocellulose showed comparable sensitivity with vWf:Ag detectable after 1:500 dilution of normal plasma. The least sensitive method was luminography in agarose gels with vWf:Ag detectable after 1:300 dilution of normal plasma. No difference existed in the banding patterns of plasmas from patients with variant vWd.

Activated protein C resistance and acute ischaemic stroke: relation to stroke causation and age.

OBJECTIVES: Resistance to activated protein C (APC) is the most frequent cause of thrombophilia and a well known risk factor for deep and cerebral vein thrombosis. Its causative role in ischaemic stroke is still a matter of debate. We undertook this study to determine the prevalence of APC-resistance in a cohort of consecutive patients with acute ischaemic stroke, especially with respect to patients' age and the underlying stroke causation. MATERIALS AND METHODS: 489 patients with proven ischaemic stroke were included in this study. Subtypes of stroke were classified according to the TOAST criteria, i. e. large artery artherosclerosis (LAA), small vessel occlusion (SVO), cardioembolism (CE), stroke of other etiology (SOE), and stroke of undetermined etiology (SUE). APC-resistance was determined with a functional method with high sensitivity and specificity for the factor V Leiden mutation. The results were compared with the prevalence of APC-resistance in healthy volunteers, all born in the same area. RESULTS: APC-resistance was found in 24 of 489 patients (4.9 %) and in 6 of the 112 (5.4 %) control subjects. In the stroke patients, APC-resistance was distributed as follows: LAA 6.5 % (9/138), SVO 3,9 % (4/104), CE 6.7 % (7/104), SOE 3.6 % (1/28), SUE 2.6 % (3/115). Prevalence of APC-resistance was not significantly different between young stroke patients (6-45 years) and older patients (7.7 % [5/65] versus 4.5 % [19/424]). CONCLUSIONS: Prevalence of APC-resistance is not increased in patients with ischaemic stroke. Additionally, no significant differences in the prevalence of APC-resistance are evident within the various stroke subtypes.

The time course and location of cerebral evoked activity associated with the processing of colour stimuli in man.

Area V4 has been located in man in the region of the fusiform gyrus on the inferior surface of the occipital lobe. Using multiple dipole source analysis on multichannel EEG recordings of visual evoked potentials to coloured 'Mondrian' stimuli in man, we have confirmed that activity is consistently seen in this area regardless of the retinal area stimulated and have obtained new information concerning its time course. Three different localized centres of activity follow the visual stimulus, with peak latencies of 90, 110 and 160 ms, and arising respectively in the region of visual areas V1, V2/V3 and V4. The time course and character of the V4 dipole activity to a colourless black-and-white Mondrian is indistinguishable from that to the coloured Mondrian, supporting the evidence that the cells of V4 are not exclusively concerned with colour processing.

Transcranial magnetic stimulation (TMS) of the brain in patients with mesiotemporal epileptic foci.

Transcranial magnetic stimulation (TMS) of the human brain is mainly used for the diagnosis of diseases with disturbed central motor conduction. Recent studies revealed controversial results concerning the possibility of a TMS-induced specific activation of epileptogenic foci in patients with localization-related epilepsies, which would make TMS an additional diagnostic tool for the presurgical localization of the primary epileptogenic zone. We applied TMS to 19 patients with complex-partial seizures and investigated its effects and safety. In 12 patients we performed TMS during scalp electroencephalogram (EEG) recordings. The remaining 7 patients with localization-related epilepsies of mesiobasal limbic seizure origin underwent EEG with additionally implanted foramen-ovale-electrodes (FOE). We did not notice any significant spike activation and even observed bilateral reduction of epileptic activity in some patients. On the contrary, hyperventilation induced a marked activation of the epileptic focus. Our findings support that TMS is safe since adverse effects did not occur. However, due to possible safety hazards, TMS in epileptic patients still requires cautious application until more data will be available.

[Molecular variants of fibrinogen]. / Molekulare Varianten des Fibrinogens.

In the final step of blood coagulation, fibrin monomers polymerize spontaneously and are covalently linked by factor XIIIa. Mutations in one of the three genes coding for the fibrinogen peptides may disturb this process and lead to diseases such as afibrinogenemia or dysfibrinogenemia, or may even cause hereditary renal amyloidosis. In the brief overview presented here we summarize some of the molecular aspects of these diseases.

Functional characterization of a novel mutation localized in the start codon of the tissue-nonspecific alkaline phosphatase gene.

Hypophosphatasia (HPP) is a rare inborn disease caused by different mutations in the tissue-nonspecific alkaline phosphatase (ALPL) gene. Previous studies showed that gene mutations could exhibit a dominant negative effect leading to a mild HPP phenotype in heterozygous carriers. In the present report we describe the clinical and functional studies of a novel mutation localized in the start codon of transcript variant 1 of the ALPL gene from a female adult heterozygous carrier. The mutation results in translation of an N-terminally truncated protein, which might be identical to the deduced protein from ALPL transcript variant 2. When overexpressed in HEK-293 cells it does not exhibit any enzymatic activity and has no significant effect on the wild type ALPL protein. Furthermore it is not attached to the cell membrane. Due to the loss of the signal peptide an intracellular misrouting and a premature degradation is obvious. Hence the new isoform deposited in the database does not produce an active protein as it is the case in the natural mutation of our patient. Since the mutation does not produce a dominant negative protein in heterozygous carriers, the clinical phenotype in our patient and her relatives is very mild with only unspecific myalgia. However the patient developed bone marrow edema of both femoral heads during lactation after delivery of a healthy child, indicating a risk to develop alterations of bone metabolism in challenge situations. Her sister complains of identical symptoms, her father shows distinct symptoms of odonto-hypophosphatasia. The question if or if not carriers of ALPL mutations in general or only with distinct genotypes can be symptomatic in normal life or in challenge situations requires systematic clinical studies.

[Idiopathic thunderclap headache: reversible vasospasm of the Arteria basilaris]. / Primärer Donnerschlagkopfschmerz: Reversibler Vasospasmus der Arteria basilaris.

Thunderclap headache describes a rare headache syndrome characterized by abrupt-onset severe headache mimicking subarachnoidal bleeding, which has to be excluded by adequate diagnostic procedures such as digital subtraction angiography. The pathophysiology is still not clear but there are an increasing number of reports which describe some kind of vasospasm of the intracranial arteries during the headache episode. Here we describe a patient with a thunderclap headache and a mid-basilar narrowing due to a reversible vasospasm.

[Acute airway obstruction in acquired hemophilia A]. / Akute Atemwegsverlegung durch erworbene Hämophilie A.

We report the case of a 67 year old patient suffering from acute airway obstruction caused by hemorrhage localized to the tongue, mouth cavity and hypopharynx, with no evidence of bleeding in his history. The patient presented initially with a globus feeling of the neck, dysphagia and a sore throat. CT scan revealed a swelling of the lingual and sublingual areas and the pharyngeal wall. Next day, there was an immediate life-threatening event caused by progressive bleeding with airway obstruction and an inability to intubate requiring coniotomy. The etiology of the hemorrhage was confirmed by finding a depletion of factor VIII and the presence of auto-antibody directed against this factor. Based on this case report and a review of the literature, we discuss the diagnosis and treatment of acquired hemophilia.

Isoelectric focusing pattern of human amniotic fluid alpha-fetoprotein.

Isoelectric focusing (IEF) of amniotic fluid alpha-fetoprotein (AFP) in thin-layer polyacrylamide gels containing 8 M urea followed by immunoblotting reveals at least nine bands, band I lying next to the cathode. Compared with 298 amniotic fluid samples from normal pregnancies, we found that the density of band V was increased in seven cases of fetal death. In 16 amniotic fluid samples from pregnancies with open neural tube defects (ONTD), band V disappeared or was markedly decreased. In seven cases with elevated AFP and positive acetylcholinesterase (AChE) due to contamination with fetal blood, no difference in pattern was observed compared with samples from normal pregnancies. It is suggested that IEF of AFP and subsequent immunoblotting are an apparently diagnostic test for ONTD and intrauterine fetal death (IUFD).

Reevaluation of lunar and Martian spectra in the mid-IR region.

A reference point method has been developed to correct infrared spectra from the moon and other celestial objects for selective absorption in the earth's atmosphere. The method is applied to lunar spectra that were obtained 2.3 km above sea level within the two atmospheric IR windows. The results indicate that SiO(2) and Al(2)O(3) are major mineral constituents in the four large surface areas analyzed in agreement with the localized probings at spacecraft landing sites. In addition, IR spectra from Martian dust clouds that were observed from the Mariner 9 spacecraft are examined. The principal sources of radiation in this case appear to be Al(2)O(3) and sulfur.