Formation of antennal lobe and mushroom body neuropils during metamorphosis in the honeybee, apis mellifera

The projections to the mushroom bodies (mbs) have been clearly described in the brain of adult honeybees (Apis mellifera). Olfactory projection neurons arborize in the lip of the calyceal neuropil, whereas visual projection neurons project to the collar. To study the maturation of this pattern of innervation, as well as the development of uniglomerular projection neurons within the antennal lobes (als), we conducted the following three studies focused on the first four stages of pupal development: mass staining of olfactory projection neurons, single cell labeling of olfactory projection neurons, and simultaneous labeling of olfactory projection neurons and visual projection neurons. Examination of whole-mount preparations with the confocal laser scanning microscope revealed that the olfactory projection neurons achieved their adult arborization pattern within their main output region, the lip of the mb calyces, earlier during development (pupal stage 1) than their dendritic processes within their main input region, the al (pupal stage 2). Simultaneous labeling experiments showed further that the fiber terminals of olfactory projection neurons and visual projection neurons did not overlap but instead occupied their respective projection areas within the mb calyces as early as pupal stage 1. We conclude that selective innervation of different subregions of the calycal neuropil precedes the segregation of glomerular units within the antennal lobe neuropil, and that the Kenyon cells themselves provide a template for the innervation of olfactory and visual projection neurons.     

Hypertrophic perineurial dysplasia in multifocal and generalized peripheral neuropathies

Two cases are described, one with a multifocal cranial and limb neuropathy of adult onset associated with optic neuropathy, and the other with a diffuse demyelinating neuropathy characterized by congenital cataract, mental retardation and progressive lower limb paresis with an onset in childhood. Extensive investigation in both failed to establish the causation. No family history of similar disorder was obtained in either case. Nerve biopsy in both showed similar perineurial abnormalities, the endoneurium being compartmentalized by hypertrophic perineurial cells that exhibited dysplastic features. The appearances resemble those described in a previously reported case of multifocal neuropathy and probably represent an unusual but non-specific response to a peripheral neuropathy.     

Increased fluorine-18 2-fluoro-2-deoxy-D-glucose (FDG) uptake in childhood CNS tumors is correlated with malignancy grade: a study with FDG positron emission tomography/magnetic resonance imaging coregistration and image fusion.

PURPOSE Positron emission tomography (PET) has been used in grading of CNS tumors in adults, whereas studies of children have been limited. PATIENTS AND METHODS Nineteen boys and 19 girls (median age, 8 years) with primary CNS tumors were studied prospectively by fluorine-18 2-fluoro-2-deoxy-D-glucose (FDG) PET with (n = 16) or without (n = 22) H(2)(15)O-PET before therapy. Image processing included coregistration to magnetic resonance imaging (MRI) in all patients. The FDG uptake in tumors was semiquantitatively calculated by a region-of-interest-based tumor hotspot/brain index. Eight tumors without histologic confirmation were classified as WHO grade 1 based on location, MRI, and clinical course (22 to 42 months). Results Four grade 4 tumors had a mean index of 4.27 +/- 0.5, four grade 3 tumors had a mean index of 2.47 +/- 1.07, 10 grade 2 tumors had a mean index of 1.34 +/- 0.73, and eight of 12 grade 1 tumors had a mean index of -0.31 +/- 0.59. Eight patients with no histologic confirmation had a mean index of 1.04. For these 34 tumors, FDG uptake was positively correlated with malignancy grading (n = 34; r = 0.72; P < .01), as for the 26 histologically classified tumors (n = 26; r = 0.89; P < .01). The choroid plexus papilloma (n = 1) and the pilocytic astrocytomas (n = 3) had a mean index of 3.26 (n = 38; r = 0.57; P < .01). H(2)(15)O-uptake showed no correlation with malignancy. Digitally performed PET/MRI coregistration increased information on tumor characterization in 90% of cases. CONCLUSION FDG PET of the brain with MRI coregistration can be used to obtain a more specific diagnosis with respect to malignancy grading. Improved PET/MRI imaging of the benign hypermetabolic tumors is needed to optimize clinical use.     

Biochemical and therapeutical studies in a case of atrophia gyrata

A thirty-six years old man from an inbred family with the typical clinical picture of Atrophia gyrata chorioideae et retinae was found to have hyperornithinemia and a partial deficiency of ornithin-ketoacid-transaminase activity. The residual activity was stimulated in vitro by high concentrations of pyridoxal phosphate. We have initiated a therapeutic study with vitamine B₆ per os accordingly.Comparitively low dosis may be sufficient for long term treatment. The necessity to start therapy early in life is emphazised. Possible mechanisms of the pathogenesis of Atrophia gyrata are discussed.

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Zusammenfassung Bei einem 36jährigen Patienten aus einer Familie mit mehrfachen Verwandtenehen wurde eine Atrophia gyrata chorioideae et retinae sowie eine Hyperornithinämie und ein Mangel an Ornithinketotransaminase festgestellt. Die Rest-aktivität dieses Enzyms wurde in vitro durch hohe Dosen von Pyridoxalphosphat stimuliert. Eine Therapie mit Vitamin B₆ per os wurde daraufhin eingeleitet.Geringe Dosen scheinen für eine Langzeitbehandlung ausreichend. Auf die Wichtigkeit einer frühzeitigen Therapie wird hingewiesen. Überlegungen zur Pathogenese der Atrophia gyrata werden dargelegt.

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Part of the results was obtained during medical thesis work of U.K.     

A scoring system for AML patients aged 70 years or older,eligible for intensive chemotherapy: a study based on a large European data set using the DATAML,SAL, and PETHEMA registries

In a context of therapeutic revolution in older adults with AML, it is becoming increasingly important to select patients for the various treatment options by taking account of short-term efficacy and toxicity as well as long-term survival. Here, the data from three European registries for 1,199 AML patients aged 70 years or older treated with intensive chemotherapy were used to develop a prognostic scoring system. The median follow-up was 50.8 months. In the training set of 636 patients, age, performance status, secondary AML, leukocytosis, and cytogenetics, as well as NPM1 mutations (without FLT3-ITD), were all significantly associated with overall survival, albeit not to the same degree. These factors were used to develop a score that predicts long-term overall survival. Three risk-groups were identified: a lower, intermediate and higher-risk score with predicted 5-year overall survival (OS) probabilities of ≥12% (n = 283, 51%; median OS = 18 months), 3–12% (n = 226, 41%; median OS = 9 months) and <3% (n = 47, 8%; median OS = 3 months), respectively. This scoring system was also significantly associated with complete remission, early death and relapse-free survival; performed similarly in the external validation cohort (n = 563) and showed a lower false-positive rate than previously published scores. The European Scoring System ≥70, easy for routine calculation, predicts long-term survival in older AML patients considered for intensive chemotherapy.Subject terms: Acute myeloid leukaemia, Risk factors     

Wertigkeit der Feinnadelpunktionszytologie bei Neoplasien der Glandula parotis

BACKGROUND: In many parts of Germany fine-needle aspiration biopsy (FNAB) is still not part of the routine preoperative diagnostic evaluation of salivary gland neoplasms. Most opponents consider the study unnecessary and recommend that all salivary gland neoplasms should be excised. OBJECTIVE: Because of this an evaluated the ability of FNAB to provide an accurate diagnosis of parotid gland neoplasms. PATIENTS AND METHOD: Between January 1992 and October 1995, 336 patients referred for operative therapy of salivary gland neoplasms underwent retrospective analysis of preoperative FNAB compared with the excised tumor histology. RESULTS: Results showed that the FNAB had a sensitivity of 93.1%, a specificity of 99.2%, a positive predictive value of 93.1%, a negative predictive value of 99.2% and an accuracy of 98.6%. Complications were observed in less than 1%. DISCUSSION: Our findings demonstrated that the FNAB is a safe diagnostic tool that has a reliable sensitivity and high specificity for the assessment of salivary gland pathology. Since many malignant salivary gland neoplasms present with a virtual lack of symptoms indicating actual malignancy we believe that there is need for FNAB in routine preoperative diagnostic testing.     

Die Aktivität der UDP-Glucuronsäurepyrophosphatase in der Leber während der Entwicklung

Zusammenfassung Die UDP-Glucuronsäurepyrophosphatase-Aktivität wurde in Lebermikrosomensuspensionen von Meerschweinchen und Ratten bestimmt. In der Leber neugeborener Meerschweinchen beträgt die Aktivität des Enzyms 10%, in der Leber neugeborener Ratten 20% der Aktivität erwachsener Tiere. Bei der Aufbewahrung der Mikrosomen bei -16°C fällt die Enzymaktivität erst vom 7. Aufbewahrungstag an allmählich ab. Die Ergebnisse zeigen, daß die ATP-Aktivierbarkeit der Glucuronyltransferase bei neugeborenen Meerschweinchen nicht auf einer Hemmung der hohen UDP-Glucuronsäure-Hydrolyse in der UDP-Glucuronsäurepyrophosphatase-Reaktion beruhen kann. Auch die Abnahme der ATP-Aktivierbarkeit der Glucuronyltransferase bei der Aufbewahrung hängt vermutlich nicht mit der Höhe der UDP-Glucuronsäurepyrophosphatase-Aktivität zusammen.

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Liver UDP-glucuronic acid pyrophosphatase activity during development

The activity of UDP-glucuronic acid pyrophosphatase has been determined in suspensions of liver microsomes from guinea pigs and rats. In the liver of newborn guinea pigs the enzyme activity exhibits 10 per cent, in the liver of newborn rats 20 per cent of the activity measured in adult animals. During storage of the microsomes at -16°C the enzyme activity remains constant during the first 7 days of storage. The data suggest that in newborn guinea pigs the glucuronyltransferase activation by ATP is not due to the inhibition of a high UDP-glucuronic acid hydrolysis, mediated by the enzyme UDP-glucuronic acid pyrophosphatase. Moreover, there is no correlation between the decline of the glucuronyltransferase activation by ATP during storage and the UDP-glucuronic acid pyrophosphatase activity.

Mit Unterstützung durch die Deutsche Forschungsgemeinschaft, Bad Godesberg.     

CD133 identifies perivascular niches in grade II–IV astrocytomas

The aim of the present study was to investigate the localization and distribution of the putative brain tumour stem cell marker CD133 in formalin fixed paraffin embedded astrocytomas. A retrospective analysis of 114 grade II, III and IV astrocytomas was undertaken. The immunohistochemical expression of CD133 in paraffin sections was analysed using morphometry. In all grades, CD133 was expressed on tumour and endothelial cells. Tumour cells were found in perivascular niches, as dispersed single cells and in pseudopalisade formations around necrosis. There was no correlation between the mean volume fraction of CD133⁺ niches and all CD133⁺ tumour cells and tumour grade. However, the volume fraction of CD133⁺ blood vessels increased significantly from 0.4% in diffuse astrocytomas to 2.2% in glioblastomas. Neither of them was related to patient survival. Double immunofluorescence stainings showed that the CD133⁺ niches both contained CD133⁺ cells with and without co-expression of the intermediate filament protein marker nestin, and only few CD133⁺/MIB-1⁺ proliferating cells were found. In conclusion, a CD133⁺ perivascular stem cell-like entity exists in astrocytomas. CD133⁺ tumour vessels may play an important role in a brain tumour stem cell context, while CD133 alone does not appear to be a specific tumour stem cell marker related to patient survival.