Ventricular enlargement, clinical correlates and treatment outcome in chronic schizophrenic inpatients.

The ventricle-brain ratio (VBR) of 42 chronic schizophrenic patients was compared with that of 42 age-matched medical controls. For the schizophrenics, the relationship of various clinical parameters to the VBR was assessed, and the outcome of 12 weeks of double-blind treatment with either risperidone or haloperidol. The results confirm that schizophrenic patients have slightly enlarged lateral ventricles compared with medical controls. Only for schizophrenics, an effect of age, but not of duration of illness, was noticed. This study does not support the validity of a clinical subdivision of chronic schizophrenic patients on the basis of the VBR. Neither negative, positive nor general psychopathological symptoms, as measured by the Positive and Negative Syndrome Scale for Schizophrenia (PANSS), were related to the VBR, nor were abnormal involuntary movements or extrapyramidal symptoms. No association between season of birth or a family history of major mental disorder and VBR could be demonstrated. Treatment response was predicted by the total PANSS score and the PANSS general psychopathology subscale score at baseline. There was a trend for patients with higher VBR to have a more or haloperidol). or haloperidol).     

Stereotactic brain biopsy in AIDS

Summary In the hope of finding a treatable condition, the need for rapid diagnosis in HIV-seropositive patients with brain lesions is apparent. In order to evaluate the efficacy of stereotactic brain biopsy in AIDS patients, we retrospectively studied 25 HIV-infected patients undergoing stereotactic biopsy. Brain lesions were identified with gadolinium-enhanced MRI and/or contrastCT. Brain biopsy was performed using the system of Riechert. From 8 up to 15 small tissue samples from one or two targets were obtained in every patient. The biopsy material was examined cytologically, histologically (including electron microscopy), immunohistochemically and, in part, by animal test and polymerase chain reaction (PCR). A definite diagnosis was achieved in 92%. Diagnosis included primary central nervous system lymphoma (PCNSL) (10), toxoplasmosis (10), progressive multifocal leukoencephalopathy (2) and one case of co-existing toxoplasmosis and cytomegalovirus infection. Two biopsies were non-diagnostic. All PCNSLs showed polymorphic B-cell populations of high malignancy; accurate classification according to the Kiel classification was not possible. In 3 lymphomas Epstein-Barr nuclear antigen (EBNA) 2-mRNA could be detected by PCR and confirmed immunohistochemically by EBNA 2 expression. In 6 cases autopsy confirmed the biopsy diagnosis. Conventional histology was not sufficiently decisive for toxoplasmosis and progressive multifocal leukoencephalopathy, so that immunohistochemistry and animal tests became very important for a final diagnosis. With the help of different morphological and molecular biological techniques stereotactic brain biopsy appears to be an effective method in the diagnosis of HIV-associated brain lesions. In view of the marked radio- and chemosensitivity of PCNSLs it is mandatory to establish an early and accurate histological diagnosis for adequate treatment.     

Modic changes following lumbar disc herniation

Only a small proportion (20%) of patients with LBP can be diagnosed based on a patho-anatomical entity. Therefore, the identification of relevant subgroups, preferably on a patoanatomical basis, is strongly needed. Modic changes have been described by several authors as being closely linked with LBP. The aims of this study were to describe the prevalence of Modic changes, their development as well as their association to LBP, previous disc contour, and surgery in patients with previous severe sciatica. This is a longitudinal cohort study where the patients were recruited from an RCT comparing two active conservative treatments, the 181 patients, who at baseline had radicular pain in or below the knee; all underwent a physical examination and MRI. MRI’s, pain history and physical examination of 166 patients were obtained at follow-up 14 months later. The prevalence of Modic changes type 1 increased from 9% at baseline to 29% at follow-up. At that time, a strong association between Modic changes and non-specific LBP was noted. Apparently, Modic changes type 1 was more strongly associated with non-specific lumbar pain than Modic changes type 2. The development of new Modic changes was closely related to the level of a previous disc herniation. A lumbar disc herniation is a strong risk factor for developing Modic changes (especially type 1) during the following year. Furthermore, Modic changes are strongly associated with LBP.     

MR Lymphography with a Lymphotropic T1-Type MR Contrast Agent: Gd-DTPA-PGM

A model system of a paramagnetic lymphotropic MR contrast agent (Gd-DTPA labeled polyglucose associated macrocomplex, PGM) for T¹-weighted MR imaging of lymph nodes in rats and rabbits was evaluated. Pharmacokinetic (tissue accumulation) and MR imaging data (optimal dose and timing parameters) were obtained in normal rats (n = 88) after subcutaneous (SC) injection of paramagnetic, radiolabeled [111In]Gd-DTPA-PGM. A rabbit model of lymph node metastases (n = 8) was ultimately used to demonstrate the potential of MR imaging with Gd-DTPA-PGM for nodal tumor detection. Maximum concentrations of Gd-DTPA-PGM were found in popliteal and paraaortic lymph nodes within 24 h after SC administration, and highest lymph node SNR values were obtained by MR imaging at this time point. The optimum imaging dose was 6–12 μmol Gd/kg. Tumor-lymph node contrast increased from 0.0 ± 1.2 precontrast to 19.2 ± 6.5 (spoiled gradient echo sequence, TR 50/TE 7/flip angle 60°) postcontrast and conspicuity of nodal metastases was improved. Gd-DTPA-PGM accumulates in lymph nodes after SC administration and significantly enhances lymph node signal intensity of normal animals but not metastatic lymph nodes.     

Surgical management of parapharyngeal cystic hygroma causing sudden airway obstruction

Parapharyngeal cystic hygroma is a rare tumor of the neck. This report describes two cases in which surgical resection was necessary to overcome sudden airway obstruction and details the surgical technique. These cases were considered "near misses" for sudden infant death syndrome (SIDS) and were revealed by computed tomography (CT) and echography to be parapharyngeal cystic hygroma. The location of this malformation could have produced sudden airway collapse and be erroneously diagnosed as SIDS. The postoperative follow-up was satisfactory and no recurrence was detected. We believe CT and echography should be included in the evaluation of such cases.     

Upregulation of the Golgi protein GP73 by adenovirus infection requires the E1A CtBP interaction domain

GP73 is a novel type II Golgi transmembrane protein that is expressed at high levels in the hepatocytes of patients with viral hepatitis (R. D. Kladney, G. A. Bulla, L. Guo, A. L. Mason, A. E. Tollefson, D. J. Simon, Z. Koutoubi, and C. J. Fimmel, 2000, Gene 249, 53-65) and is induced in cultured cells by infection with viruses including adenoviruses. Its biological function and the mechanisms by which its expression may be regulated by viral infection are unknown. Here we report that GP73 is induced at the RNA and protein level in human Hep3B hepatoma cells infected by human Ad5 and Ad2. Hep3B cells were infected with wild-type or mutant adenoviruses. GP73 expression was measured by RNase protection assay, immunoblotting, or immunofluorescence microscopy. GP73 RNA and protein levels were strikingly induced following infection. The rise in GP73 expression coincided with the appearance of the adenovirus E1A and DBP proteins and preceded the expression of the fiber protein, a marker of the late phase of infection. Infection did not affect the expression of giantin, GPP130, or golgin-84, three integral Golgi membrane proteins with structural similarities to GP73. Mapping studies using a panel of mutant adenoviruses demonstrated that the E1A C-terminus, specifically its CtBP interaction domain (CID), is required for GP73 expression. Subsequently, Hep3B cells were transiently transfected with plasmids expressing wild-type or mutant E1A proteins. These studies confirmed that E1A induced GP73 expression via the CID. Our studies establish GP73 as a novel adenovirus-induced cellular protein whose expression is regulated through the CID of the E1A protein.     

Assay for the specificity of monoclonal antibodies in crossed immunoelectrophoresis

A method is described based on crossed immunoelectrophoresis of a complex antigen mixture in agarose gel followed by incubation of the gel with the monoclonal antibody. The bound monoclonal antibody is detected by the use of a secondary enzyme-labelled antibody.Using this technique we have been able to identify the precipitate arc in crossed immunoelectrophoresis of major histocompatibility complex (MHC) class I molecules in a mixture of all detergent solubilized cell membrane molecules by means of a monoclonal antibody, the specificity of which was known independently to be against MHC class I molecules. In other experiments using the same technique we demonstrated the reaction of a monoclonal antibody specific for chicken Ig light chains.     

Chlorotetracycline Induces calcium mediated shape changes in human erythrocytes

Calcium was localized in the red cell membrane by light microscopy using chlorotetracycline hydrochloride (CTC) as chelate probe. Treating human erythrocytes with CTC dissolved in saline free of divalent cations, leads to a 530 nm fluorescence emission in the cell border and to characteristic cell shape changes which were evaluated to assess intramembrane calcium distribution. CTC prevented and reverted erythrocyte crenation induced either by washing or superfusing the cells with saline. The ionophore A23187, EGTA and glucose depletion depressed the shape modifying effect of CTC. Thus, CTC appears to act on red cell shape by complex formation with membrane associated calcium. This is further confirmed by the failure of degraded CTC, devoid of metal binding capacity, to modify the crenated shape. The CTC effect can be reverted by superfusing the erythrocytes with CTC-free medium. Thus, calcium binds more tightly to the membrane than to CTC and is not displaced by the antibiotic. If the bilayer couple hypothesis [Sheetz, M.P., Singer, S.J., Proc. Natl. Acad. Sci. USA 71, 4457-4461 (1974)]applies, crenation is reverted by expansion of the inner membrane half relative to the outer membrane half. Expansion of the inner membrane half results from intercalation of CTC which binds to calcium. Thus, calcium in the red cell membrane preferentially occupies the inner leaflet of the bilayer.     

A unique exonic splice enhancer mutation in a family with X-linked mental retardation and epilepsy points to a novel role of the renin receptor

The renin-angiotensin system (RAS) is essential for blood pressure control and water-electrolyte balance. Until the discovery of the renin receptor, renin was believed to be mainly a circulating enzyme with a unique function, the cleavage of angiotensinogen. We report a unique mutation in the renin receptor gene (ATP6AP2) present in patients with X-linked mental retardation and epilepsy (OMIM no. 300423), but absent in 1200 control X-chromosomes. A silent mutation (c.321C>T, p.D107D) residing in a putative exonic splicing enhancer site resulted in inefficient inclusion of exon 4 in 50% of renin receptor mRNA, as demonstrated by quantitative RT-PCR. Analysis of membrane associated-receptor molecular forms showed the presence of full-length and truncated proteins in the patient. Functional analysis demonstrated that the mutated receptor could bind renin and increase renin catalytic activity, similar to the wild-type receptor, but resulted in a modest and reproducible impairment of ERK1/2 activation. Thus, our findings confirm the importance of the RAS in cognitive processes and indicate a novel specific role for the renin receptor in cognitive functions and brain development.