Blood Lymphocyte Proliferation Response to Pollen Extract as a Monitor of Immunotherapy

In a study of immunotherapy 41 children with seasonal rhinoconjunctivitis due to deciduous tree pollen allergy were monitored by means of symptom scoring, patient self-evaluation, conjunctival provocation tests and lymphocyte proliferation in vitro to the allergen. The lymphocyte responsiveness to birch pollen decreased significantly during the first year of immunotherapy. However, neither the lymphocyte responsiveness before treatment nor changes in lymphocyte reactivity during the immunotherapy correlated with the clinical efficacy of the therapy as evaluated by changes in symptom scores, self-evaluation or conjunctival provocation test changes in the individual patients. The results indicate the lymphocyte responsiveness to an allergen cannot be used to select patients for immunotherapy, i.e. to predict whether a patient would benefit from immunotherapy or not, or to evaluate the effects of immunotherapy after beginning the treatment. However, lymphocyte proliferation response to an allergen indicates clinical sensitivity.     

Effects of lithium on water intake and renal concentrating ability in rats with vasopressin-deficient diabetes insipidus (Brattleboro strain)

Male and female Long Evan rats and Brattleboro rats with ADH-deficient diabetes insipidus were treated with lithium administered in the diet for 12 weeks. The plasma lithium level was about 1 mmol/l in all groups. Lithium caused polydipsia and polyuria and lowering of renal concentrating ability in normal rats. In rats with ADH deficiency lithium tended to increase water intake, but did not influence spontaneous urine osmolality or maximal urine osmolality during water deprivation. The results indicate that the renal concentrating defect caused by lithium in rats can be explained by ADH-blockade as the only mechanism. However, there is circumstantial evidence that lithium in addition may stimulate thirst mechanisms by an ADH-independent action.     

Die Erythrokinetik bei Osteomyelofibrose

Zusammenfassung Bei 20 Patienten mit Osteomyelofibrose wurden Erythrocytenbildung und Erythrocytenzerstörung mit Hilfe von Cr⁵¹ und Fe⁵⁹ z. T. nach simultaner Verabreichung dieser Isotope untersucht. Die Erythrocytenlebensdauer war oft verkürzt, jedoch meist nicht hochgradig. Nur bei wenigen Kranken war eine aktive Beteiligung der Milz an der vorzeitigen Zerstörung der Erythrocyten nachweisbar. Das Plasmaeisenturnover war fast stets erhöht, die Eiseninkorporation in die Erythrocyten vermindert. Eine extramedulläre Erythropoese war meist, aber nicht ausnahmslos, durch Oberflächenmessung nachzuweisen. Sie fand überwiegend in der Milz statt, doch war die Leber in zwei Fällen der wichtigste Ort der Erythrocytenbildung. Eine Produktion von Erythrocyten im Knochenmark war bei der Hälfte der entsprechend untersuchten Fälle noch in geringem Maße vorhanden. Die komplexe Korrelation dieser Befunde mit den hämatologischen Daten wurde besprochen und die Indikation zur Splenektomie erörtert.

---

Summary Production and destruction of erythrocytes were investigated in 20 patients suffering from myelofibrosis. Cr⁵¹ and Fe⁵⁹ were administered simultaneously. The erythrocyte life span was shortened frequently, but only moderately in most instances. In few patients only the spleen played an active part in the accelerated red cell destruction. The plasma iron turnover was increased in most cases, the incorporation of iron into the erythrocytes was decreased. Extramedullary erythropoiesis was demonstrated by means of surface activity measurements in most but not in all patients. It was localised most frequently in the spleen. In two cases, however, the liver was the most important site of erythrocyte production. Some degree of medullary erythropoiesis was seen in 50 percent of our cases. The correlation between these results and the remaining hematological findings as well as the question of when to remove the spleen are discussed.

---

---

Unter technischer Mitarbeit von FräuleinRenate Roesch, FräuleinMargret Philips und FräuleinIngrid Westmattelmann.

---

Die Arbeit wurde durchgeführt mit Unterstützung der Deutschen Forschungsgemeinschaft.     

Barriers to Dissemination: Exploring the Criticisms of Behavior Therapy for Tics

The review by Cook and Blacher (2007 ) suggests that behavior therapy for tic disorders is indeed efficacious. Given the empirical support for these treatments, researchers should begin to place effort on examining various strategies for treatment dissemination. The current article addresses possible barriers to dissemination, focusing specifically on various concerns that have been raised by many medical and psychological care providers. The validity of these concerns is examined in the context of existing data. In addition, limitations of the current literature and future directions for research are discussed.     

Trophic effect of the sympathetic nervous system on the early development of the rat parotid gland: A quantitative ultrastructural study

Rats were sympathetically denervated on one side by avulsion of the superior cervical ganglion either immediately after birth (within 4 hr) or when the salivary glands were fully developed. Nine weeks after ganglionectomy the parotid glands were subjected to microscopical studies. As shown by the lack of specific fluorescence, sympathetic denervation caused an almost total depletion of catecholamines in the acini. This was further substantiated at the electron microscopic level using KMnO⁴ as fixative. No alterations in either gland weight or in acinar cell size were noticeable after adult sympathectomy. On the other hand, neonatal denervation caused a decrease in gland weight as well as acinar cell hypotrophy. The mean volume of individual acinar cells was reduced by roughly 25% and the granule volume density by about 50%. Also the mean volume of individual granules was decreased. These findings indicate an important role for the sympathetic nerve system in the maturation of the rat parotid gland.     

Studies on the Histamine Releasing Effect of Bee Venom Fractions and Compound 48/80 on Skin and Lung Tissue of the Rat

Two bee venom fractions, F I and F II, obtained by gel filtration, and compound 48/80, were shown to release histamine from skin and lung tissue of the rat. F I is the phosphatidase A containing fraction, and F II contains a basic polypeptide. Dose-response relationships, the time course of the histamine release, and the influence of enzyme inhibitors were studied. The results with F II and compound 48/80 were similar, suggesting that the two substances activate the same kind of release mechanism. It is concluded that F II is not related to the earlier described bee venom polypeptides melittin and aparnin. The mode of action of phosphatidase A was distinctly different from that of F II or compound 48/80. The results are consistent with the assumption that it acts in a “non-specific.” way by hydrolysing tissue phosphatides to lyso compounds, which in turn damage the tissue.     

Exploring cancer register data to find risk factors for recurrence of breast cancer – application of Canonical Correlation Analysis

Background  

A common approach in exploring register data is to find relationships between outcomes and predictors by using multiple regression analysis (MRA). If there is more than one outcome variable, the analysis must then be repeated, and the results combined in some arbitrary fashion. In contrast, Canonical Correlation Analysis (CCA) has the ability to analyze multiple outcomes at the same time.     

Expression and secretion of active mouse TIMP-1 using a baculovirus expression vector

Mouse TIMP-1, one of the tissue inhibitors of metalloproteinases important in regulating turnover of extracellular matrix in both normal and pathological tissues, was previously expressed inE. coli in an inactive, nonglycosylated state that required refolding to become functional. Due to the difficulty of renaturation, an alternative to the prokaryotic expression system was sought. Since we are interested in studying the pharmacodynamics and pharmacokinetics of TIMP locally administered by controlled delivery to mice with experimentally induced arthritis, we also needed an efficient way of producing active TIMP in large quantities. Using the pBlueBacII transfer vector, we generated a recombinant baculovirus that in Sf9 cells could express glycosylated mouse TIMP-1 to about 3 mg of active protein/liter conditioned medium.     

A genomewide linkage analysis for prostate cancer susceptibility genes in families from Germany

Prostate cancer is a complex disease with a substantial genetic contribution involved in the disease risk. Several genomewide linkage studies conducted so far have demonstrated a strong heterogeneity of susceptibility. In order to assess candidate regions that are particularly relevant for the German population, we performed a genomewide linkage search on 139 prostate cancer families. A nonparametric method (Zlr scores), using GENEHUNTERPLUS, was applied at 500 markers (panel P1400, deCODE), with an average spacing of 7.25 cM. In the entire family collection, linkage was most evident at 8p22 (Zlr=2.47, P=0.0068), close to the previously identified susceptibility gene MSR1. Further local maxima with Zlr>2 (P<0.025) were observed at 1q, 5q and 15q. In a subgroup of 47 families, which matched the Johns Hopkins criteria of hereditary prostate cancer, suggestive linkage was found on 1p31 (Zlr=3.37, P=0.00038), a previously not described candidate region. The remaining 92 pedigrees, with no strong disease history, revealed a maximum Zlr=3.15 (P=0.00082) at 8q13, possibly indicating a gene with reduced penetrance or recessive inheritance. Our results suggest pronounced locus heterogeneity of prostate cancer susceptibility in Germany. In the present study population, the MSR1 gene could play a significant role. Other conspicuous loci, like 1p31 and 8q13, need further investigation in order to verify their relevance and to identify candidate genes.     

Upregulation of TGF-beta, FOXP3, and CD4+CD25+ regulatory T cells correlates with more rapid parasite growth in human malaria infection

Understanding the regulation of immune responses is central for control of autoimmune and infectious disease. In murine models of autoimmunity and chronic inflammatory disease, potent regulatory T lymphocytes have recently been characterized. Despite an explosion of interest in these cells, their relevance to human disease has been uncertain. In a longitudinal study of malaria sporozoite infection via the natural route, we provide evidence that regulatory T cells have modifying effects on blood-stage infection in vivo in humans. Cells with the characteristics of regulatory T cells are rapidly induced following blood-stage infection and are associated with a burst of TGF-beta production, decreased proinflammatory cytokine production, and decreased antigen-specific immune responses. Both the production of TGF-beta and the presence of CD4+CD25+FOXP3+ regulatory T cells are associated with higher rates of parasite growth in vivo. P. falciparum-mediated induction of regulatory T cells may represent a parasite-specific virulence factor.