Transforming growth factor-beta-mediated regulation of human peripheral blood mononuclear cell proliferation as detected with phosphorothioate antisense oligodeoxynucleotides.

Transforming growth factor-beta (TGF-beta) is a potent cytokine that has influence upon immunosuppressive as well as proinflammatory processes. In this context we have investigated the role of endogenous TGF-beta in human peripheral blood mononuclear cells (PBMCs) by TGF-beta 1 phosphorothioate antisense oligodeoxynucleotides (TGF-beta 1-S-ODNs). In short-term cultures (up to 3 days), TGF-beta 1-S-ODNs-treated, interleukin 2-activated PBMCs displayed a growth advantage (up to 148%) compared to nonsense or untreated controls as measured by cell counting and [3H]thymidine incorporation.

Reduced echogenicity of brainstem raphe specific to unipolar depression: a transcranial color-coded real-time sonography study.

Echogenicity of the brainstem raphe was assessed in patients with major depression, bipolar affective disorders, and schizophrenia and compared with healthy adults employing transcranial color-coded real-time sonography. Forty probands were enrolled in each group. A highly significant reduction in raphe echogenicity was detected only in patients suffering from major depression.

[The status of transcranial color-coded real time ultrasound in diagnosis of cerebral lesions].

Transcranial color-coded real-time sonography (TCCS) combines transcranial Doppler sonography and color-coded B-mode scanning of the brain parenchyma and cerebral vessels. This technique is not invasive and a broad spectrum of intracerebral lesions such as vascular lesions (ischemic stroke and intracerebral hemorrhage, aneurysms, arteriovenous malformations, arteriosclerotic vascular degeneration) and parenchymal lesions (brain tumors, degenerative and neuropsychiatric disorders) can be disclosed. Compared with MRI and CT, the ultrasound system is movable.

Transcranial color-coded real-time sonography of intracranial veins. Normal values of blood flow velocities and findings in superior sagittal sinus thrombosis.

Sonographic findings in patients with superior sagittal sinus thrombosis were compared to those in healthy adults. Two patients with angiographically verified superior sagittal sinus thrombosis were examined by transcranial color-coded real-time sonography (TCCS) after intravenous application of a pulmonary stable ultrasound contrast agent. For comparison, 10 patients without venous pathology had contrast-enhanced TCCS; in addition, 30 healthy adults had plain TCCS to determine the identification rate for deep and superficial venous segments and to define normal values of venous blood flow velocities.

Magnetic resonance image findings of spinal intramedullary abscess caused by Candida albicans: case report.

We present the clinical, serological, and radiological features of a patient with a spinal intramedullary abscess caused by Candida albicans. Antimycotic treatment was successful, and no neurosurgical approach was necessary.

Preoperative and postoperative follow-up in high-grade gliomas: comparison of transcranial color-coded real-time sonography and computed tomography findings.

Twenty patients with high-grade gliomas were prospectively studied by pre- and postoperative transcranial color-coded real-time sonography (TCCS) and CT, to determine the sensitivity of TCCS in the identification of residual tumor and tumor regrowth. Each patient was subjected to preoperative and early postoperative CT (postoperative day 1) and TCCS examinations (postoperative days 6 to 8) and subsequent CT and TCCS follow-up examinations within a time interval of 6 weeks to 3 months. In eight patients, a total of 15 biopsy specimens were intraoperatively obtained from the wall of the resection cavity.

Degeneration of substantia nigra in chronic Parkinson's disease visualized by transcranial color-coded real-time sonography.

To detect morphologic abnormalities in Parkinson's disease (PD), we examined 30 patients with PD and 30 age- and sex-matched nonparkinsonian controls by transcranial color-coded real-time sonography (TCCS). In 12 severely affected PD patients, the echogenicity of the substantia nigra was distinctly increased. In the remaining 18 PD patients and in all controls, the substantia nigra was poorly visualized or nondetectable by TCCS.

Investigation of the 1H NMR visibility of lactate in different rat and human brain cells.

In recent years, 1H MRS has been used in a number of studies to measure the lactate content of brain, and it is generally assumed that the methyl resonance at 1.3 ppm reflects the total amount of lactate present in the tissue. However, reduced NMR visibility of lactate has recently been reported for blood, heart and skeletal muscle as well as for bacteria.

Cloning of a novel malignant melanoma-derived growth-regulatory protein, MIA.

Growth and progression of malignant melanoma cells is influenced by a complex network of growth-stimulating and -inhibiting factors produced by both the tumor cells and the local environment. Here we report the purification and molecular cloning of a novel growth regulating protein, designated melanoma inhibitory activity (MIA) and provide a preliminary functional characterization. MIA is translated as a 131-amino acid precursor and processed into a mature 107-amino acid protein after cleavage of a putative secretion signal.

Reliability of transcranial colour-coded real-time sonography in assessment of brain tumours: correlation of ultrasound, computed tomography and biopsy findings.

Transcranial colour-coded real-time sonography (TCCS) was carried out in 25 patients with brain tumours to determine whether this noninvasive method provides additional information about the extent of solid tumour, its differentiation from oedema, and its tissue components. All 25 patients had serial computed tomography (CT)-guided stereotactic biopsies. Comparison of ultrasound, CT and histological findings revealed that the vast majority of contrast enhancing areas on CT were hyperechogenic (32/33; 97%) and contained tumour tissue (29/32; 91%).

In vitro studies of cytokine-mediated interactions between malignant glioma and autologous peripheral blood mononuclear cells.

The humoral interactions between three malignant glioma early-passage cell cultures and in vitro interleukin (IL)-1 alpha- and IL-2-activated autologous peripheral blood mononuclear cells (PBMC's) were investigated, employing standard and modified (separated by permeable membranes) mixed lymphocyte tumor cell (MLTC) cultures. In modified MLTC's, glioma cells clearly inhibit proliferation of PBMC's (up to 60%), whereas lymphokine-activated PBMC's enhance glioma cell growth up to 12-fold, as determined by 3H-thymidine incorporation assays. Glioma cells produce both stimulatory (IL-6) and inhibitory proteins (transforming growth factor-beta) for PBMC's.

Doppler enhancement with SH U 508A in multiple vascular regions.

Purpose: To determine the magnitude and duration of peripheral vascular and cardiac Doppler signal enhancement after intravenous administration of contrast agent SH U 508A.

Materials And Methods: Suboptimal cardiac or peripheral vascular Doppler examinations were evaluated. A total of 75 intravenous bolus injections were made in 30 patients.

Contribution of transcranial color-coded real-time sonography to the etiopathogenetic classification of middle cerebral artery stenosis.

Transcranial color-coded real-time sonography (TCCS) and cranial computed tomography were applied to patients with middle cerebral artery (MCA) stenosis to evaluate whether these techniques may disclose additional aspects of the pathophysiology of the stenotic lesion. In 15 patients with MCA stenosis identified by transcranial Doppler sonography, the echogenicity of the stenotic segment was estimated subjectively by TCCS. The density of the stenotic segment, prior to being detected by TCCS, was quantified by computed tomography.

Vascularization of primary central nervous system tumors: detection with contrast-enhanced transcranial color-coded real-time sonography.

Purpose: To study the potential of contrast material-enhanced transcranial color-coded real-time sonography (TCCS) in detection of primary intracranial tumor vascularization.

Materials And Methods: Primary central nervous system (CNS) tumors in 28 patients were examined with TCCS before and during administration of a transpulmonary, stable, galactose, microparticle-based ultrasound (US) contrast agent. All patients underwent cranial computed tomography and magnetic resonance imaging; nine patients also underwent intraarterial digital subtraction angiography.

Echogenicity of the brainstem raphe in patients with major depression.

A novel transcranial ultrasound technique was used to detect differences in the echogenicity and echotexture of the brainstem dorsal raphe nucleus in 20 patients with major depression compared with 20 age- and sex-matched healthy adults. Transcranial color-coded real-time sonography visualized the mesencephalic and pontine brainstem and its midline structure. The echogenicity of the raphe was classified in a four-point scale.

Efficacy SH U 508 A (Levovist) as blood pool enhancer in the Doppler evaluation of multiple vascular regions.

SH U 508 A (Levovist) as a blood pool enhancer to investigate multiple vascular regions with Doppler ultrasonography. Thirty patients with sub-optimal cardiac or peripheral vascular Doppler exams received 75 intravenous contrast bolus injections in all to investigate the intensity and the duration of Doppler signal enhancement after the i.v.

High-resolution one- and two-dimensional 1H MRS of human brain tumor and normal glial cells.

Astrocytoma (WHO grade II, III), glioblastoma, malignant melanoma, and normal glial cell cultures, established from biopsies, were investigated by 1H MRS. At a 1H resonance frequency of 500 MHz (11.75 T) a high spectral resolution was achieved in 1D 1H spectra; in conjunction with 2D shift-correlated (COSY) MRS, resonances of alanine, aspartate, choline, creatine, glutamate, glutamine, hypotaurine, myo-inositol, phosphocreatine, phosphoryl-ethanolamine, phosphoryl-choline, lactate, lysine, N-acetylaspartate, taurine, threonine and valine could be identified.

Surgical intervention and heparin-anticoagulation improve prognosis of rhinogenic/otogenic and posttraumatic meningitis.

It is still controversial, whether early surgical removal of infectious material and heparin-anticoagulation to reduce vascular complications will improve outcome in acute meningitis. In the present pilot-study 40 patients with acute or delayed post-traumatic or oto-/rhinogenic purulent bacterial meningitis were analysed for neurological outcome by using the Glasgow outcome score (GOS) and the Tuthill functional score; patients were treated either by early surgical revision of the septic focus (Group 1, within 6 days, n = 15), late surgery (Group 2, later than 6 days, n = 19), or no surgery at all (Group 3, n = 6). All patients, independent of surgical approach, received therapeutic heparin-anticoagulation.

Identification of ventricular enlargement and estimation of intracranial pressure by transcranial color-coded real-time sonography.

Transcranial color-coded real-time sonography (TCCS) was applied to 26 patients with ventricular enlargement to quantify the ventricular size and to estimate intracranial pressure. Intracranial pressures, as determined by lumbar, epidural, or ventricular tonometry, ranged from 6.5 to 55 cm H2O (8 patients had pressures > 18 cm H2O).

In vitro studies on interaction of 4-hydroperoxy-ifosfamide and radiotherapy in malignant gliomas.

Drug-radiation multimodal chemotherapy for malignant brain tumor cells was stimulated in vitro by a recently developed computer program, based on evaluation of 3D-response surfaces and interaction isoboles. Three malignant glioma tumor cell cultures (HTZ17, 146 and 209 B) were sequentially treated in vitro by increasing doses of 4-hydroperoxy-ifosfamide, according to in vivo/in vitro pharmacokinetic correlation (0.01 to 10 microM), and increasing single doses of Gamma-radiation (clinical60Co-radiotherapy unit, 0.

Autocrine growth regulation in neuroectodermal tumors as detected with oligodeoxynucleotide antisense molecules.

The cell lines of three neuroectodermal tumors, two glioblastomas (HTZ-146, HTZ-17) and one melanoma (HTZ-19) were established and screened for the expression of growth factors by northern blotting and immunochemical methods. All three tumors were positive for platelet-derived growth factor- (PDGF-) A-, -B-chain, and basic fibroblast growth factor (bFGF) messenger ribonucleic acids. Cultured cells as well as original tumor material were also positive for PDGF-AA-, PDGF-BB, and bFGF protein, as shown by immunochemistry.

Imaging of the vertebrobasilar system by transcranial color-coded real-time sonography.

The vertebrobasilar system was investigated in 75 persons by TCCS to evaluate the applicability and diagnostic capacity of this transcranial Duplex technique. Transforaminal and transtemporal acoustic windows were employed to identify the vertebral arteries, basilar artery (PCA) and major branches of the vertebrobasilar system. The frequency of identifying the basilar artery and the PCA ranged from 84 to 94% but was poor for the distal segment of the basilar artery (45.

Autoinduction of platelet derived growth factor (PDGF) A-chain mRNA expression in a human malignant melanoma cell line and growth inhibitory effects of PDGF-A-chain mRNA-specific antisense molecules.

Autoinduction of PDGF-A-chain mRNA's was demonstrated in cells of a human malignant melanoma cell line (HTZ 19), indicating a PDGF-induced amplification of an autocrine growth factor loop mechanism. PDGF-alpha receptors were detected by immunocytochemistry in HTZ 19 melanoma cells. Exogenously administered PDGF-AA exerted an increase in cell proliferation by 70% at 200 ng/ml PDGF in serum-supplemented cell culture medium.

The effect of transforming growth factor-beta 2-specific phosphorothioate-anti-sense oligodeoxynucleotides in reversing cellular immunosuppression in malignant glioma.

This in vitro study was aimed at restitution of transforming growth factor (TGF)-beta 2-mediated suppression of T-lymphocyte activation within malignant gliomas. In early-passage tumor cell cultures of two glioblastomas (HTZ-153 and HTZ-209) and one malignant astrocytoma classified as World Health Organization Grade III (HTZ-243), autologous peripheral blood mononuclear cells were activated by interleukin-1 alpha and interleukin-2 in vitro (lymphokine-activated killer cells) and tested for cytotoxic and proliferative activity. In expression studies (Western blot and Northern hybridization) of all three tumors, TGF-beta could be detected at the protein and messenger ribonucleic acid (mRNA) levels.

Contrast-enhanced transcranial color-coded real-time sonography. Results of a phase-two study.

Background And Purpose: Transcranial color-coded real-time sonography has been developed as a promising new bedside procedure to monitor central nervous system parenchymal and vascular pathology; the present study was designed to investigate the potential role of galactose microparticles (SH U 508 A) as a new ultrasound contrast-enhancing agent for transcranial sonography.

Methods: Ten patients (four women and six men, 24-63 years of age) with a broad spectrum of central nervous system pathology were investigated by transcranial color-coded real-time sonography in a phase-two clinical study. After conventional ultrasound examination, all patients received a maximum of six injections of 10 ml with 200, 300, or 400 mg/mL SH U 508 A.