Expression of the c-erbB-2-encoded oncoprotein and progesterone receptor in human meningiomas

The present study investigated the expression of c-erbB-2 in 59 meningiomas, including different histological subtypes and anaplastic variants, by immunocytochemistry and molecular biological techniques. Immunohistochemistry using the monoclonal antibody FWP-51 directed against c-erbB-2-encoded oncoprotein gp185 demonstrated variable degrees of immunoreactivity in all meningiomas. The intensity of immunostaining correlated with the degree of expression as assessed by Western analysis in 28 meningiomas using polyclonal antiserum 21N. There was no correlation between the degree of expression and histological variants. Immunoreactivity of all menigiomas was distinctly less intense, however, than that of the human breast cancer cell line SK-BR-3, and slightly lower than that of brain metastases of breast and ovarian carcinomas that served as positive controls for both methods. By Southern analysis all meningiomas showed a single copy of the c-erbB-2 gene. Non-neoplastic arachnoid cap cells also exhibited c-erbB-2 expression and the degree of immunoreactivity was comparable with the majority of meningiomas. These data argue against an overexpression of c-erbB-2 in meningiomas, but rather indicate a cell-type-specific constitutive expression of the c-erbB-2 gene product in meningiomas and their putative progenitor cells. Since a subgroup of meningiomas is known to express progesterone receptors (PR), gp185 immunoreactivity was compared to the hormone receptor status using monoclonal antibody KD68. Fifty-six percent meningiomas showed PR immunoreactivity, but there was no statistically significant correlation with the degree of gp185 expression.This study was supported by a grant of the Tumorzentrum Heidelberg/Mannheim (M.K., No. 10028060)     

肱骨干骨折--髓内钉与钢板固定的比较

总体而言，这些报道提示：采用髓内钉治疗肱骨干骨折较采用钢板带来更多的并发症，尤其是采用顺行人路。同时，这些报道没有提供确切的证据证明何种方法在骨折愈合、减少感染或上肢总体功能上优于另一种。     

Wilson's disease tremor is associated with magnetic resonance imaging lesions in basal ganglia structures.

Wilson's disease (WD) is an inherited disorder of copper metabolism yielding marked motor deficits, including a severely disabling tremor. As a structural correlate of the disease, a variety of cerebral abnormalities has been revealed. However, the relationship between motor deficits and cerebral lesions has remained largely unknown. Here, we investigated correlation between WD tremor and cerebral magnetic resonance imaging (MRI) findings. Cerebral MRI abnormalities in 6 symptomatic WD patients were compared to findings in 6 asymptomatic WD patients and 10 healthy controls. All patients were treated with long-term copper chelating therapy. Motor symptoms including tremor were determined by Unified Parkinson's Disease Rating Scale Part III (UPDRS-III). MRI findings in symptomatic WD patients revealed significant symmetric T2*-weighted hypointense signal alterations of globus pallidus, head of the caudate nucleus, and substantia nigra. In contrast, MRI of asymptomatic WD patients did not differ from healthy controls. Correlation analysis revealed a significant positive correlation between MRI basal ganglia lesions and UPDRS action tremor score. Our results demonstrate for the first time that Wilson's disease tremor is associated with lesions of the globus pallidus, the head of the caudate nucleus, and the substantia nigra.     

Effect of depressive symptoms on survival after heart transplantation

OBJECTIVE: This study explored the value of preoperative self-reported assessment for depression and anxiety in patients who had undergone heart transplantation (HTx). The initial sample was divided into subgroups of patients with ischemic (ICMP) and dilated cardiomyopathy (DCMP). Patient depression and anxiety scores were measured in both subgroups and their impact on pre- and postoperative mortality investigated. METHOD: An initial sample of 152 patients with either ICMP (N = 57) or DCMP (N = 95) and end-stage heart disease awaiting heart transplantation were assessed in a multidimensional longitudinal study, including psychological and somatic variables. One hundred and three patients received a HTx and were followed up for a mean of 4.4 years. Proportional hazard models were computed to test for the influence of psychosocial and somatic factors on outcome. RESULTS: Preoperative depression and state anxiety scores were significantly higher in the ICMP group. In addition to donor and recipient age, ICMP patients in the preoperative high depression group also showed a significantly higher mortality after HTx. This result remained significant even after controlling for sociodemographic and somatic variables. CONCLUSIONS: Patient self-reported depression, but not anxiety, can contribute to the identification of subgroups of patients with an unfavorable outcome after HTx. It therefore may be helpful to screen for depression, particularly in patients with an ischemic cause of their end-stage heart disease. Specific intervention programs should be further developed and evaluated.     

Seven novel and four recurrent point mutations in the factor VIII (F8C) gene

Haemophilia A is a X‐linked bleeding disorder, caused by deficiency in the activity of coagulation factor VIII due to mutations in the corresponding gene. The most common defect in patients is an inversion of the factor VIII gene that accounts for nearly 45% of individuals with severe hemophilia A. Point mutations and small deletions/insertions are responsible for the majority of cases with moderate to mild clinical course and for half of the severe hemophilia A occurrences. The majority of these mutations are “private”, because of the high mutation rate for this particular gene. We report on eleven pathological changes in the factor VIII sequence detected in male patients with haemophilia A or in female obligate carriers. Seven of these mutations are novel [E204N, E265X, M320T, F436C, S535C, N2129M and R2307P] and four have been previously identified [V162M, R527W, R1966X, and R2159C]. Genotype‐phenotype correlations and computer prediction analysis on the effect of missense mutations on the secondary structure of the factor VIII protein are performed and the relationships evaluated. © 2001 Wiley‐Liss, Inc.     

Keratin immunohistochemistry in renal cell carcinoma subtypes and renal oncocytomas: a systematic analysis of 233 tumors

Keratin immunohistochemistry represents a widely applied differential diagnostic tool in surgical pathology. To investigate the value of keratin subtyping for the diagnosis among histological subtypes of renal cell carcinoma and oncocytomas, we performed a detailed immunohistochemical study, applying 22 different monoclonal keratin antibodies on a large series of 233 renal tumors [125 conventional, 22 chromophobe, and 20 papillary (12 type-1, 8 type-2 tumors) cancers and 66 oncocytomas] using a tissue microarray technique. Immunoreactivity for keratin 7, 8, 18, and 19 was present in all tumor entities, albeit in varying quantities. With antibodies directed against keratins 8 and 18, oncocytomas showed a distinct perinuclear and punctate dot-like pattern, which was not observed in renal cancer specimens. The only tumors showing immunoreactivity for keratin 20 were two type-2 papillary cancers. All other monospecific keratin antibodies yielded consistently negative results. Overall, in contrast to some recent publications, keratin subtyping generally appeared to be of additional value only for the differentiation of renal epithelial tumors. Hence, with respect to differential diagnostic value, Hales colloidal iron stain and vimentin immunostaining are still the most useful tools in renal tumor pathology.     

CXCR4 and Gab1 cooperate to control the development of migrating muscle progenitor cells

Long-range migrating progenitor cells generate hypaxial muscle, for instance the muscle of the limbs, hypoglossal cord, and diaphragm. We show here that migrating muscle progenitors express the chemokine receptor CXCR4. The corresponding ligand, SDF1, is expressed in limb and branchial arch mesenchyme; i.e., along the routes and at the targets of the migratory cells. Ectopic application of SDF1 in the chick limb attracts muscle progenitor cells. In CXCR4 mutant mice, the number of muscle progenitors that colonize the anlage of the tongue and the dorsal limb was reduced. Changes in the distribution of the muscle progenitor cells were accompanied by increased apoptosis, indicating that CXCR4 signals provide not only attractive cues but also control survival. Gab1 encodes an adaptor protein that transduces signals elicited by tyrosine kinase receptors, for instance the c-Met receptor, and plays a role in the migration of muscle progenitor cells. We found that CXCR4 and Gab1 interact genetically. For instance, muscle progenitors do not reach the anlage of the tongue in CXCR4;Gab1 double mutants; this target is colonized in either of the single mutants. Our analysis reveals a role of SDF1/CXCR4 signaling in the development of migrating muscle progenitors and shows that a threshold number of progenitor cells is required to generate muscle of appropriate size.     

Cyst-like cerebral lesions in tuberous sclerosis

Known brain manifestations of tuberous sclerosis (TSC) are cortical sclerotic tubera, giant cell astrocytomas, subependymal calcified nodules in the lateral walls of the lateral ventricles, and white matter heterotopias. In addition, small cyst-like lesions in the white matter have been described. We report on three TSC patients with hitherto undescribed large cyst-like cerebral lesions in subcortical and white matter locations. We emphasize that cystoid brain degeneration is a rare but typical cerebral manifestation of TSC and suggest that, in patients with such lesions, TSC should be taken into consideration.