Histological and cytological criteria in the diagnosis of malignant melanomas by cryostat sections

Summary Although cryostat sections in general allow a distinction to be made between malignant melanomas and other pigmented lesions in clinically doubtful cases, the differential diagnosis may be difficult. The histological and cytological criteria taken into account can be classified as major, minor, and insufficient. Knowing the diagnostic value of each makes a conventionally established diagnosis safer. Variance analysis does not contribute to the problem but it can nevertheless be shown that the evaluation of six major criteria makes a quick and reliable cryostat section diagnosis possible. If these results are confirmed in a prospective study it would be a decisive step on the way to a quicker and safer cryostat section diagnosis of malignant melanoma, even for the less experienced histopathologist.The results published here were presented in part at the DDG meeting 1980 at Westerland/SyltWe are grateful to Miss Schubert, Institute of Biomathematics of the University of Munich, for the statistical evaluations     

Involvement of E-cadherin and beta-catenin in germ cell tumours and in normal male fetal germ cell development

Intercellular contacts, mediated by E-cadherin, are essential for germ cell migration and maturation. Furthermore, it has been suggested that decrease or loss of E-cadherin correlates with tumour progression and invasive behaviour. beta-catenin is involved in a number of different processes, including cell--cell interaction when bound to cadherins, and determination of cell fate in pluripotent cells when activated via the Wnt signal-transduction pathway. To shed more light on the role of these factors in normal fetal germ cell development and the pathogenesis of germ cell tumours (GCTs), the present study investigated the presence and localization of E-cadherin and beta-catenin by immunohistochemistry. E-cadherin was only weakly expressed in or absent from fetal germ cells of the second and third trimesters, and was not expressed in carcinoma in situ/intratubular germ cell neoplasia unclassified (CIS/ITGCNU) and gonadoblastoma, the precursor of an invasive GCT in dysgenetic gonads. In GCTs, it was generally not expressed in seminoma and dysgerminoma, but was found in the vast majority of non-seminoma cells. beta-catenin was found in the cytoplasm of fetal germ cells at all gestational ages and in spermatogenesis in post-pubertal testes. It was also present in CIS/ITGCNU and gonadoblastoma. Whereas seminomas and dysgerminoma were negative, non-seminoma cells were frequently found to express beta-catenin. Expression of both factors therefore reflects the degree of differentiation of these tumours. No differences for either E-cadherin or beta-catenin were observed between samples of tumours resistant or sensitive to chemotherapy, and E-cadherin expression did not correlate with vascular invasion. E-cadherin and beta-catenin therefore play a role in both normal and malignant germ cell development and differentiation that warrants further investigation, but they seem to be of limited value as predictive or prognostic factors in GCTs.     

Psychoeducational and cognitive-behavioral strategies in the management of bipolar disorder

Despite advances in the pharmacologic treatment of bipolar disorder, it is clear that additional strategies are needed to provide patients with longer-term mood stability. Recent years have witnessed the development of a number of psychosocial strategies for bipolar disorder that are design as adjuncts to ongoing pharmacotherapy. In this article we describe psychoeducational and cognitive-behavioral approaches to the management of bipolar disorder, with emphasis on broader treatment packages that can be offered by cognitive-behavior therapists working in specialty bipolar clinics, as well as specific strategies that can be integrated into standard pharmacotherapy for the disorder. A growing body of evidence documents the potential value of these interventions, and large-scale studies are underway, including the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), which will provide outcome on these interventions from the perspective of large, multicenter trials.     

Postnatal expression of transport proteins involved in acid–base transport in mouse kidney

The kidney plays a major role in maintaining and controlling systemic acid–base homeostasis by reabsorbing bicarbonate and secreting protons and acid-equivalents, respectively. During postnatal kidney development and adaptation to changing diets, plasma bicarbonate levels are increasing, the capacity for urinary acidification maturates, and the final morphology and distribution of intercalated cells is achieved. In adult kidney, at least two types of intercalated cells (IC) are found along the collecting duct characterised either by the expression of AE1 (type A IC) or pendrin (non-type A IC) where non-type A IC are found only in the convoluted distal tubule, connecting tubule and cortical collecting duct. Here we investigated in mouse kidney the relative mRNA abundance, protein expression levels and distribution of several proteins involved in renal acid–base transport, namely, the Na⁺/HCO₃ ^– cotransporter NBC1 (SLC4A4), the Na⁺/H⁺-exchanger NHE3 (SLC9A3), two subunits of the vacuolar H⁺-ATPase [ATP6V0A4 (a4), ATP6V1B1 (B1)], the Cl^–/HCO₃ ^– exchangers AE1 (SLC4A1) and pendrin (SLC26A4). Relative mRNA abundance of all transport proteins was lowest at day 3 after birth and increased thereafter in parallel with protein levels. The numbers of type A and non-type A IC in the cortical collecting duct (CCD) increased from day 3 to days 18 and 24, whereas the number of IC in the CCD with apical staining for the vacuolar H⁺-ATPase subunits a4 and B1 decreased from day 3 to days 18 and 24, respectively. In addition, cells with characteristics of non-type A IC (pendrin expression, basolateral expression of vacuolar H⁺-ATPase subunits) were found in the inner and outer medulla 3 days after birth but were absent from the medulla of 24-day-old mice. Taken together, these results demonstrate massive changes in mRNA and protein expression levels of several acid–base transporters during postnatal kidney maturation and also show changes in intercalated cell phenotype in the medulla during these processes.     

Afterpotentials following penicillin-induced paroxysmal depolarizations in rat hippocampal CA1 pyramidal cells in vitro

Epileptic discharges were induced by superfusion of rat hippocampal slices with penicillin. Under these conditions the neurons generated paroxysmal depolarization shifts (PDS) after electrical stimulation of Schaffer collaterals. The PDS were followed by large afterhyperpolarizations lasting about 2 s. The mechanisms causing these afterhyperpolarizations were studied in CA1 pyramidal cells. A late component of the after hyperpolarizations, which determined their overall duration, was blocked by intracellular application of EGTA and reduced by superfusion with 8-Br-cAMP. In the same neurons these drugs had a comparable effect on after hyperpolarizations following depolarizing current injections; it was therefore concluded that the late component of the PDS afterhyperpolarizations was caused by a slow Ca²⁺-activated K⁺ current. An initial fast component of PDS afterhyperpolarizations, which peaked about 60 ms after PDS onset, was reduced by EGTA but not affected by 8-Br-cAMP suggesting that the fast Ca²⁺-activated K⁺ current also contributed to the PDS afterhyperpolarizations. Superfusion of the slice with the -aminobutyric acid B receptor (GABA_B) antagonists phaclofen or 5-aminovalerate reduced the amplitude of the afterhyperpolarizations during the first 1000 ms but did not affect the late Ca²⁺-dependent component, indicating that a GABA_B-mediated K⁺ inhibitory postsynaptic potential (IPSP) contributed to the PDS afterhyperpolarization. Intracellular injection of Cl^– revealed that an early part of the afterhyperpolarizations lasting about 500 ms was Cl^–-dependent. This component was blocked by superfusion of the slices with bicuculline, suggesting that a GABA_A-mediated Cl^– IPSP contributed to the PDS afterhyperpolarization. The experiments show that different synaptic and intrinsic components with different time courses participate in the generation of PDS afterpotentials.     

Retrograde tracing studies of subdivisions of the orbicularis oculi muscle in the rhesus monkey

Functionally and anatomically, the orbicularis oculi (OO) muscle can be subdivided in a pretarsal, a preseptal, and an orbital portion. In the rhesus monkey, fluorescent and neuronal retrograde tracing experiments were performed in the pretarsal or the orbital portion of the OO muscle, or both, using fast blue, diamidino yellow, and wheat germ agglutinin-horseradish peroxidase as tracers. The preseptal portion was not investigated because of close anatomical relationships to the other portions. It was found that motoneurons innervating the OO muscle are located exclusively within the intermediate subnucleus of the motor facial nucleus. The upper pretarsal motoneurons show a specific distribution in the dorso-rostral border area of the intermediate subnucleus, representing a dome-like organization, while lower pretarsal motoneurons are situated more ventrally in the adjacent area. The pretarsal motoneurons are all located dorsally in the rostral half and the upper part of the caudal half of the intermediate subnucleus. The upper pretarsal portion is subserved by about one third of the total intermediate motoneuron population. The size of the upper pretarsal motoneurons is similar to that of the motoneurons of the lower pretarsal portion of the OO muscle and falls, for the vast majority, into the large motoneuronal range. Motoneurons belonging to the upper and lower orbital portions are located ventrally and are more randomly distributed in the rostral half of the intermediate subnucleus. The size of orbital motoneurons varies from small to large. The large fraction of pretarsal motoneurons may reflect the specific function of the upper pretarsal portion during rapid and highly coordinated movements of the eyelids in different types of blinking. Received: 18 September 1997 / Accepted: 13 March 1998     

Anxiety psychopathology predictive of outcome in patients with panic disorder and depression treated with imipramine, alprazolam and placebo

This study examines clinical predictors of outcome for patients with panic disorder and depression in a 16 week, placebo-controlled trial of alprazolam and imipramine (n = 126). Baseline global severity of illness and phobic avoidance were differentially predictive of acute response to treatment. Patients in the mild to moderate range of global distress experienced smaller degrees of improvement on alprazolam than on imipramine at week 4. At endpoint, the relative effectiveness of the active medication versus placebo was diminished in patients with higher levels of phobic avoidance. This relationship was not evident for completers, suggesting that the adverse effects of avoidance on outcome after sustained treatment was reduced.     

Helicobacter pylori gastric infection in gnotobiotic beagle dogs.

Establishment of infection with Helicobacter pylori and gastritis in nonhuman species is currently only successful in gnotobiotic piglets. This study was designed to determine whether H. pylori will colonize the gastrointestinal tract of gnotobiotic dogs. Gnotobiotic beagle pups were derived by standard methods. Group A (five dogs) was orally challenged with 3 x 10(8) H. pylori at 7 days of age. Group B (two dogs) received only peptone water but was contact-exposed beginning on day 23 postinfection (p.i.). Necropsy was performed on dogs on day 30 p.i. H. pylori colonized the stomach of all dogs (groups A and B). Urease map analysis correlated with the microbiologic findings and indicated that the density of colonization was less than that observed in human tissue. Organisms were also recovered from the pharynx, esophagus, duodenum, and rectum of 1, 2, 2, and 1 dog, respectively. All group A and one group B dog developed serum immunoglobulin G specific for H. pylori by day 30 p.i. Gross lesions were restricted to the stomach and consisted of small (less than 1 mm) lymphoid follicles. Microscopically, there were focal to diffuse lymphoplasmacytic infiltrates with follicle formation and mild to moderate infiltration of neutrophils and eosinophils in the gastric lamina propria. With the Warthin-Starry silver stain, organisms were seen on the surface of the gastric epithelial cells, beneath the mucus layer. We conclude that H. pylori colonizes the stomachs of gnotobiotic dogs for at least 1 month and the lesions resemble those seen in humans. H. pylori is transmissible by contact from infected to noninfected dogs.     

Blood coagulation and fibrinolysis after long-duration treadmill exercise controlled by individual anaerobic threshold

For rehabilitation training it is recommended that the intensity of exercise should be clearly below the individual anaerobic threshold (IAT). We investigated blood coagulation, particularly endogenous thrombin potential (ETP) and fibrinolysis following a standardized treadmill (TR) ergometer test at 90% IAT for 60–120 min. Sixteen healthy male non-smokers underwent the TR test. Blood samples were taken after a 30-min rest, immediately after exercise, and 2 h after exercise completion. Extrinsic and intrinsic total (TTP_ex+in) and endogenous (ETP_ex+in) thrombin potential, prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT), plasmin-2-antiplasmin complex (PAP), D-dimer, tissue plasminogen activator antigen and activity (tPA-AG and tPA-ACT) and plasminogen activator inhibitor type 1 antigen and activity (PAI-1-AG and PAI-1-ACT) were measured. Immediately after TR, F1+2, TAT and TTP_ex+in were increased (P<0.05) while ETP_ex+in remained unchanged. In contrast, PAP, D-dimer, tPA-AG, tPA-ACT (P<0.05) were distinctly enhanced while PAI-1-ACT was decreased (P<0.05) immediately after exercise. The changes in tPA-AG, tPA-ACT, and PAI-1-ACT were reversed to nearly baseline while the enhancement in PAP and D-dimer was prolonged by more than 2 h after exercise. Long-duration exercise between 60 and 120 min controlled by IAT (90%) on a TR ergometer only implicates a small increase in thrombin generation markers and total (free and ₂-macroglubulin-bound thrombin), but not in endogenous (free) thrombin potential alone. In contrast, fibrinolysis is distinctly increased after this type of exercise. Endurance exercise with an intensity below 90% IAT and a duration below 2 h generates a more favourable condition for fibrinolysis than for blood coagulation in healthy young subjects. Data are given as mean (SD).