Alterations of visual search strategy in Alzheimer's disease and aging

Visual search, characterized by eye fixation patterns, was examined in 8 patients with Alzheimer's disease (AD), 8 cognitively intact, age-matched individuals, and 8 young control participants as they searched for a number among a nonlinear array of letters on a large computer screen. Among the 3 groups, target detection accuracy differed and detection time increased linearly. There were more fixations, and fixation duration was significantly longer in the AD patients than in the other 2 groups. These factors contributed to the lengthening of target detection time. This qualitative difference in the architecture of visual search between AD and aging may reflect a specific deficit in the disengagement of visual spatial attention, a prolongation of saccade initiation, or inefficiency in planning a search strategy.     

Apoptose: Bcl-2 ein Schlüsselprotein für den programmierten Zelltod

Zusammenfassung Die Realisation, da? Tumorwachstum nicht nur durch Zellproliferation, sondern auch durch ein l?ngeres Zellüberleben bedingt sein kann, er?ffnet vollst?ndig neue Perspektiven in der Grundlagenforschung wie in der klinischen Tumorforschung. Die Apoptose ist deshalb heute Kernpunkt wissenschaftlicher Diskussion. Im Zentrum des derzeitigen Interesses ist neben den Steuermechanismen des programmierten Zelltodes auch der Nachweis seiner klinischen Bedeutung für die verschiedenen Tumorentit?ten. Aktuelle Untersuchungen zur Embryogenese, zum physiologischen Zellumsatz und zu epithelialen und hormonabh?ngigen Tumoren weisen das Protoonkogen bcl-2 als einen wichtigen Regulator der Apoptose aus. Nach eigenen Untersuchungen hat der Pathomechanismus Apoptose auch für maligne mesenchymale Tumoren eine Bedeutung.      

Age-associated changes in the stimulatory effect of transforming growth factor beta on human osteogenic colony formation

Previous studies have indicated that the mitogenic responsiveness of human bone cells may change with age. In the present study, we examined whether aging affects the capacity of transforming growth factor beta (TGF-beta) to stimulate the colony formation of human osteoprogenitor cells. Outgrowths of bone cells from 98 iliac crest biopsies were plated at a density of 25 cells/cm2 and cultured for 3 weeks in the presence of 10% fetal calf serum. Approximately 5% of the plated cells gave rise to clonal colonies. TGF-beta (10(-11) M) significantly increased the estimated number of cells per colony. However, the stimulatory effect of TGF-beta significantly declined with donor age (r = -0.26, P = 0.01). Whereas TGF-beta raised the average number of cells per colony in cultures from donors below the age of 50 years by 136+/-50%, the average increase was only 43+/-16% in donors older than 60 years. These data raise the possibility that aging may be associated with a declining capacity of TGF-beta to enlarge the pool of bone cells that can be generated from a single human osteoblast progenitor cell.     

Impaired temperature regulation in rats after anosmia induced peripherally or centrally

Bilateral olfactory bulbectomy or destruction of the olfactory epithelium of rats resulted in elevated body temperature in room temperature, and lowered water/food ratio in 30 degrees ambient temperature. The results suggest the involvement of the olfactory system in the thermoregulation.     

Pharmacokinetic studies of high-dose metoclopramide with and without forced diuresis

Summary The pharmacokinetics of high-dose metoclopramide (10 mg/kg body wt. in five infusions of 2 mg/kg body wt. each) was studied in 11 patients (5 females, 6 males) in two groups: group A with and group B (consisting of five patients) without forced diuresis. When the drug was infused, forced diuresis had no influence on the pharmacokinetics of metoclopramide (serum level after the 1st infusion was 851±361 ng/ml in group A versus 840±348 ng/ml in group B; after the 5th infusion it was 2,005±588 ng/ml in group A versus 2,463±1,350 ng/ml in group B). There were significant differences in the 24-h serum levels (582±308 ng/ml in group A versus 379±170 ng/ml in group B;P<0.05) and in the elimination half life (8.5±2.6 h in group A versus 6.1±1.1 h in group B;P<0.05). The results demonstrate that the dosage regimen originally suggested by Gralla for cytostatic drugs, with forced diuresis for high-dose metoclopramide therapy, may also be applied, with no dosage reduction, with to other cytostatic drugs which do not require forced diuresis.     

Myoepitheliale Tumoren der Kopfspeicheldrüsen

This tutorial focuses on myoepithelial tumors of salivary glands, an entity with heterogeneous cytomorphology and inconsistent immunophenotype. Moreover, the clinical course cannot be predicted reliably from cytomorphological and immunophenotypic analysis. This heterogeneity causes problems in routine diagnostic, so that diagnosis ultimately rests on conventional histology. In a representative series of myoepitheliomas and malignant myoepitheliomas, antibodies against cytokeratins 5/6, S 100 protein and vimentin produced the most consistent reactivity profile. Staining for cytokeratins 5/6 is a useful addition to the established immunohistologic marker panel in the work-up of myoepitheliomas, because of its reliable expression in most cases and because it may underline the epithelial nature of the lesion. Comparative genomic hybridisation (CGH) profiles of myoepitheliomas and myoepithelial carcinomas showed no chromosomal aberration in less than 50% of myoepithelial carcinomas, so that CGH is of limited help in a given case. In a case that was represented in three separately localized manifestations of the disease that differed in their CGH profiles, gross genetic aberrations suggest to be acquired during tumor progression and should raise the suspicion of malignancy. Thus, diagnosis of myoepithelial tumors of salivary glands has to rest on morphological grounds with support of a restricted panel of immunohistologic markers.     

Buchbesprechungen

Ohne Zusammenfassung     

The nephronophthisis complex

Summary The clinical and morphological findings are described in 27 children with nephronophthisis. Seventeen children were considered as sporadic cases. In 10 familial cases the presumed mode of inheritance was autosomal recessive. The clinical picture was rather uniform: polyuria-polydipsia, hyposthenuria, anemia, growth retardation, and azotemia with progressive renal failure. Six patients presented with tapeto-retinal degeneration. In a further seven children other ocular changes were detected. Two female siblings showed additional non-renal manifestations: mental retardation, pulmonary emphysema, skeletal anomalies, and congenital hepatic fibrosis.Renal histology displayed a chronic sclerosing tubulo-interstitial nephropathy with extensive tubular atrophy and dedifferentiation. Medullary cysts were frequently found in end-stage kidneys. Immunofluorescence was either non-specific or completely negative. On electron microscopy, the tubular basement membrane changes predominated: thickening, lamellation, splitting, and deposition of microfibrils within the increased basement membrane substance. Detailed light- and electron microscopic findings were non-specific but the overall morphologic picture was characteristic and even diagnostic in conjunction with the clinical presentation.A recurrence of nephronophthisis in transplanted kidneys has not been observed.The pathogenesis of nephronophthisis is obscure but with respect to the morphologic findings a primary or secondary tubular basement membrane defect seems very likely.Our experience suggests that nephronophthisis is a frequent cause of chronic renal failure in children and commonly associated with non-renal abnormalities. To avoid the separation of different syndromes presenting with a uniform renal disease but various non-renal manifestations, we suggest that the term nephronopthisis complex be used.Presented in part at the 63th Annual Meeting of the German Society of Pathology, Stuttgart 1979