Immunoglobulin Gene Rearrangement in Plasma Cell Dyscrasias: Detection of Small Clonal Cell Populations in Peripheral Blood and Bone Marrow

The bone marrow (BM) and peripheral blood (PB) samples of 71 patients with plasma cell dyscrasias were analysed by the Southern blot technique for the presence of clonal immunoglobulin (Ig) gene rearrangements. 53% of BM samples examined were archival material such as air dried BM slides or frozen trephine biopsies. The results were related to bone marrow plasmacytosis as determined by cytology and flow cytometry, and other clinical parameters. Clonal Ig gene rearrangements were found in BM samples of 45 (83%) of 54 MM patients and in 3 of 6 patients with monoclonal gammopathy of unknown significance (MGUS). Clonal cell populations in the PB were detected in 11 (30%) of 37 examined MM patients, but in none of the patients with MGUS or solitary plasmacytoma of bone. PB involvement was associated with progressive disease. Circulating monoclonal cells were significantly associated with higher M-protein levels (p 0.05). Thus, circulating clonal precursor cells are encountered more frequently in active MM.     

Expression profiling identifies the CRH/CRH-R1 system as a modulator of neurovascular gene activity.

Corticotropin-releasing hormone receptor type 1 (CRH-R1)-deficient mice display reduced anxiety-like behavior, a chronic corticosterone deficit, and an impaired neuroendocrine stress response caused by disruption of the hypothalamic-pituitary-adrenocortical (HPA) axis. The molecular substrates and pathways of CRH/CRH-R1-dependent signaling mechanisms underlying the behavioral phenotype as well as the consequences of lifelong glucocorticoid deficit remain largely obscure. To dissect involved neuronal circuitries, we performed comparative expression profiling of brains of CRH-R1 mutant and wild-type mice using our custom made MPIP (Max Planck Institute of Psychiatry) 17k cDNA microarray. Microarray analysis yielded 107 genes showing altered expression levels when comparing CRH-R1 knockout mice with wild-type littermates. A significant proportion of differentially expressed genes was related to control of HPA and hypothalamic-pituitary-thyroid (HPT) axes reflecting not only the disturbance of the HPA axis in CRH-R1 mutant mice but also the interplay of both neuroendocrine systems. The spatial analysis of regulated genes revealed a prevalence for genes expressed in the cerebral microvasculature. This phenotype was confirmed by the successful cross-validation of regulated genes in CRH overexpressing mice. Analysis of the cerebral vasculature of CRH-R1 mutant and CRH overexpressing mice revealed alterations of functional rather than structural properties. A direct role of the CRH/CRH-R1 system was supported by demonstrating Crhr1 expression in the adult murine cerebral vasculature. In conclusion, these data suggest a novel, previously unknown role of the CRH/CRH-R1 system in modulating neurovascular gene expression and function.     

Altered corticomotor representation in patients with Parkinson's disease.

In 6 patients with Parkinson's disease (PD) and 6 age-matched controls, transcranial magnetic stimulation was applied at 56 regions over the motor cortex and premotor cortex of each hemisphere, with the first dorsal interosseous (FDI) muscle of both hands activated at 15% maximum voluntary contraction during stimulation. For each site, motor evoked potential (MEP) landmarks were recovered, including MEP amplitude, MEP onset latency, and silent period duration. Scaled MEP amplitudes were used to construct individual cortical maps of the FDI muscles. The maps revealed an anterior displacement of the muscle representation in PD patients. This anterior shift over motor cortical areas may reflect increased contributions of corticocortical connections between motor cortex and premotor cortical areas, possibly enhanced by the visual feedback aspect of the task. These alterations may reflect adaptations to the impairments in striatocortical circuits in PD.     

Differential effect of catechol-O-methyltransferase Val158Met genotype on emotional recognition abilities in healthy men and women.

The catechol-O-methyltransferase (COMT) Val158Met polymorphism modulates executive functions and working memory and recent neuroimaging studies implicate an association with emotional processing. We examined the relationship between the COMT Val158Met polymorphism and facial emotion recognition and differentiation in 100 healthy individuals. Compared to Met homozygosity, Val homozygosity was associated with better and faster recognition of negative facial expressions such as anger and sad. Our study provides evidence for a possible influence of the COMT polymorphism on emotion recognition abilities in healthy subjects. Additional research is needed to further define the neurocognitive phenotypes associated with COMT polymorphisms.     

Chronic obstructive pulmonary disease--psycho-social issues and treatment goals.

Chronic Obstructive Pulmonary Disease (COPD) is one of the major chronic debilitating diseases frequently seen in hospital settings. The disease appears usually after the age of fifty and often predicts a shortened life span. The present paper is a review of the literature relating to the psychological aspects of this disease. The impact on psychosocial coping and adaptation will be discussed, specifically the effects on marital and sexual functioning and the quality of life of the patient. Psycho-social treatment goals useful to the COPD patient and his family will be raised and elaborated on.     

Akromioklavikulargelenkverletzungen

There is some controversy over the treatment of acromioclavicular injuries. The use of the Rockwood classification as the basis for decisions on whether operative or nonoperative treatment is indicated is discussed critically, and the authors' preferred operative technique is described and illustrated by examples. We treat injuries classified according to the Rockwood classification as types I and II with conservative methods. In type III injuries the patient's age, job and free time activities determine whether or not surgery is indicated. In the case of type IV or type VI injuries we always perform temporary internal fixation of the acromioclavicular joint, using transarticular K-wire fixation or hookplate osteosynthesis. Satisfactory results of both operative and nonoperative treatment are reported in the literature. The authors' own results are presented.     

Activation of a Ca2+-dependent K+ current by the oncogenic receptor protein tyrosine kinase v-Fms in mouse fibroblasts

We investigated the effects of the receptor-coupled protein tyrosine kinase (RTK) v-Fms on the membrane current properties of NIH3T3 mouse fibroblasts. We found that v-Fms, the oncogenic variant of the macrophage colony-stimulating factor receptor c-Fms, activates a K⁺ current that is absent in control cells. The activation of the K⁺ current was Ca²⁺-dependent, voltage-independent, and was completely blocked by the K⁺ channel blockers charybdotoxin, margatoxin and iberiotoxin with IC₅₀ values of 3nM, 18 nM and 76nM, respectively. To identify signalling components that mediate the activation of this K⁺ current, NIH3T3 cells that express different mutants of the wildtype v-Fms receptor were examined. Mutation of the binding site for the Ras-GTPase-activating protein led to a complete abolishment of the K⁺ current. A reduction of 76% and 63%, respectively, was observed upon mutation of either of the two binding sites for the growth factor receptor binding protein 2. Mutation of the ATP binding lobe, which disrupts the protein tyrosine kinase activity of v-Fms, led to a 55% reduction of the K⁺ current. Treatment of wild-type v-Fms cells with Clostridium sordellii lethal toxin or a farnesyl protein transferase inhibitor, both known to inhibit the biological function of Ras, reduced the K⁺ current amplitude to 17% and 6% of the control value, respectively. This is the first report showing that an oncogenic RTK can modulate K⁺ channel activity. Our results indicate that this effect is dependent on the binding of certain Ras-regulating proteins to the v-Fms receptor and is not abolished by disruption of its intrinsic protein tyrosine kinase activity. Furthermore, our data suggest that Ras plays a key role for K⁺ channel activation by the oncogenic RTK v-Fms. Received: 19 November 1997 / Accepted: 21 January 1998     

Radiologic search for embolized leaflets of prosthetic heart valves: A report of two cases

In a radiologic search for embolized leaflets of Edwards-Duromedics bileaflet valves in 2 patients, the embolized fragments were localized in the iliac vessels using computed tomography. Sonography was successful in one case and standard X-ray films of the abdomen were negative in both cases.In vitro investigations with Björk-Shiley and Edwards-Duromedics leaflets suggested that standard X-ray films of the abdomen and pelvis should be considered as the first investigational technique. If negative, computed tomography of the lower abdomen should be done.