Production of tumor necrosis factor and other cytokines by astrocytes stimulated with lipopolysaccharide or a neurotropic virus.

Rat astrocytes, immunologically competent glial cells of the central nervous system (CNS), released a variety of cytokines after activation. Lipopolysaccharide-stimulated astrocytes produced tumor necrosis factor (TNF) as demonstrated by Northern blot analysis using a mouse TNF probe and by functional assay. Biological activity of rat astrocyte-derived TNF was neutralized by rabbit antiserum against recombinant murine TNF. Stimulation of astrocytes by lipopolysaccharide also activated the interleukin 1 and interleukin 6 genes. We have also investigated whether a neurotropic paramyxovirus, Newcastle disease virus, triggers cytokine production by astrocytes. This virus induced astrocytes to produce TNF, lymphotoxin, interleukin 6, and alpha- and beta-interferons. Thus, stimulation by endotoxin and virus activated distinct, yet overlapping, sets of cytokine genes. We propose that astrocytes and the cytokines they produce may play a significant role in the pathogenesis of immunologically and/or virally mediated CNS disease, in CNS intercellular communication, and in the interactions between the nervous and immune systems.     

Enhancement of hepatic hemangiomas with levovist on coded harmonic angiographic ultrasonography.

OBJECTIVE: To evaluate the pattern of contrast enhancement with Levovist on coded harmonic angiographic ultrasonography of hepatic hemangiomas. METHODS: Twenty hemangiomas were evaluated with coded harmonic angiographic ultrasonography and a microbubble contrast agent. Verification of the diagnosis of a hemangioma was made by means of dynamic computed tomography (n = 8), dynamic magnetic resonance imaging (n = 1), radionuclide scanning (n = 6), or follow-up ultrasonography (n = 5). Ultrasonographic images were obtained before contrast agent administration and with a bolus injection of 2.5 g of a microbubble contrast agent (300 mg/mL Levovist; Schering AG, Berlin, Germany) every 10 to 15 seconds for 5 minutes. The contrast enhancement patterns of the 20 hemangiomas were assessed. RESULTS: The tumor diameters as measured on ultrasonography were 7 to 97 mm (mean, 26.7 mm). Of the 20 hemangiomas, peripheral globular enhancement with progressive centripetal fill-in was shown in 15 (75%), rimlike enhancement with progressive centripetal fill-in was shown in 2 (10%), and homogeneous enhancement was shown in 1 (5%). In the remaining 2 lesions (10%), the enhancement patterns could not be seen, because they were not found on coded harmonic angiographic ultrasonography. CONCLUSIONS: Coded harmonic angiographic ultrasonography with a microbubble contrast agent can depict the typical enhancement pattern in most hepatic hemangiomas.     

Effect of cisplatin chemotherapy on extracortical tissue formation in canine diaphyseal segmental replacement

The reconstruction of large bone and joint defects after the resection of malignant tumors remains a major challenge. Chemotherapy has significantly lowered the risk of metastasic disease, but complications associated with reconstructive techniques continue to result in late morbidity. In the present study, biomechanical torsion testing, gait analysis, and histomorphometric and scanning electron microscopic evaluations of 24 dogs were used to examine the effects of preoperative and postoperative administration of cisplatin on the biologic fixation of a porous-coated segmental replacement prosthesis. The chemotherapy consisted of four cycles of cisplatin administered at a dosage of 75 mg/m:² preoperatively or postoperatively. The healing was enhanced by use of an autogenous corticocancellous bone graft. The graft was placed evenly around the prosthesis and the adjacent femoral cortex. Mechanical analyses of torsional stiffness, yield strength, and maximum strength revealed no statistically significant differences between the groups at 12 weeks. Such lack of difference was mainly due to the penetration of highly organized fibrous tissue into the porous surface; this provided strong fixation of the implant to bone even in the absence of bone ingrowth. Although bone ingrowth into the prostheses was not affected, electron microscopic, histomorphometric, and radiologic analyses showed a clear difference in the formation of new bone around the prosthesis. Preoperative chemotherapy did not alter the formation of new bone, but specimens from animals treated postoperatively with cisplatin showed significantly less bone graft resorption and less new bone formation. Hence, the effect of cisplatin administration caused only a temporary delay, not a permanent effect, on extracortical capsule formation. The formation of extracortical bone and soft tissue might prevent debris-incised osteolysis and, therefore, prevent late complications by forming a tight capsule around the bone-prosthetic interface.     

Immunoscintigraphy in the detection of tuberculosis with radiolabelled antibody fragment against Mycobacterium bovis bacillus Calmette-Guérin: a preliminary study in a rabbit model.

Immunoscintigraphy with radiolabelled monoclonal antibodies is widely used to detect solid tumours, but only a few trials have been carried out concerning the specific in vivo localization of an inflammatory process. The purpose of this study was to investigate the detectability of tuberculous foci utilizing this method with radiolabelled bacillus Calmette-Guérin (BCG)-specific F(ab')2 in rabbits. All of the tuberculous lesions (n = 8) were clearly visualized on serial scintigraphy for up to 48 h after injection of the antibody. Immunohistochemical and Ziel-Neelson staining of the tuberculous lesions confirmed the presence of the tuberculous antigens and bacilli. It failed to demonstrate any sustained retention of the BCG-specific antibody fragment in the control group with syphilitic orchitis (n = 2). Therefore, the specific in vivo localization of tuberculosis is feasible by immunoscintigraphy.     

Umbilical portion of recipient's left portal vein: a useful vascular conduit in dual living donor liver transplantation for the thrombosed portal vein.

We considered performing living donor liver transplantation (LDLT) in a larger-size recipient. When the recipient was large-sized, or when the donor liver was severely steatotic or had a right-to-left volume discrepancy. We devised dual living donor liver transplantation (DLDLT) to make up for graft size insufficiency and to secure the donor's safety. However, portal vein thrombosis (PVT) presented a challenge for DLDLT because of the need for intact right and left portal veins for the implantation of both liver grafts. Our 52-year-old male patient with hepatitis B cirrhosis had suffered from repeated esophageal and gastric variceal bleeding and underwent 2 trials of a transjugular intrahepatic portosystemic shunt (TIPS). He developed TIPS occlusion and PVT involving the area just above the spleno-mesenteric confluence to the right and left PV. Also, the right PV orifice was destructed and difficult to isolate because of severe periportal inflammation and neointima growth in the TIPS mesh. The patient's two sons were inadequate for donation because of right-to-left volume discrepancy. Therefore, DLDLT using 2 left lobes was necessary to compensate for graft-size insufficiency and to secure donor safety, and we substituted an intact umbilical portion of recipient's left PV for the destroyed right PV. The patient recovered well, and liver function has been normal for more than a year. In conclusion, the umbilical portion of recipient's left PV can be a useful vascular substitute for the reconstruction of a thrombosed main portal branch in DLDLT.     

Cyclin E, p27 and mutant p53 do not predict the prognosis in AJCC stage II colorectal carcinomas.

BACKGROUND/AIMS: Carcinogenesis is characterized by the abnormal regulation of cell cycle. The abnormal expression of the regulators of cell cycle may be related to the prognosis. Since the clinical significance of the expression of the three proteins in colorectal carcinomas is still controversial, we evaluated the prognostic value of the expression of cyclin E, p27 and mutant p53 in stage II colorectal cancer. METHODS: The expression levels of cyclin E, p27 and mutant p53 proteins in 41 patients with stage II colorectal carcinomas were analyzed by immunohistochemistry. RESULTS: In the univariate analysis, the level of CEA at diagnosis was associated with disease relapse. In the multivariate analysis, the clinicopathological variables such as age, gender, site of primary tumor, tumor size, state of tumor differentiation and preoperative plasma CEA level were not associated with disease relapse. When Kaplan-Meier survival curves were constructed to determine the prognosis, cyclin E, p27 and mutant p53 expressions did not predict poor prognosis. CONCLUSIONS: Our results suggested that the expression of cyclin E, p27 and mutant p53 proteins did not predict the clinical outcome in the stage II colorectal carcinomas.     

Benign osteoblastoma of the occipital bone: Case report and literature review

We present a case of benign osteoblastoma of the occipital bone. Benign osteoblastoma is an uncommon primary bone tumor, which usually involves the vertebrae and the long bones. This tumor rarely develops in the calvaria, showing a preference for the temporal and frontal bones when it does. To the best of our knowledge, this case is only the eighth reported case of benign osteoblastoma confined to the occipital bone. A 20‐year‐old male presented with a mild tender mass lesion of the occipital area, just below the lambda. Plain X‐ray films and CT scans demonstrated an osteolytic mass surrounded by the sclerotic rim within the diploic space. MRI proved to be effective for the evaluation of the intracranial and intraosseous extensions of the tumor. However, it was very difficult to formulate a differential diagnosis against other osteoblastic tumors, or osteoid osteoma, in view of its radiological appearance. The final diagnosis was obtained by careful consideration of the histopathological characteristics of the tumor combined with its clinical and radiological features. Although generally regarded as benign, a complete resection is preferred over conventional curettage as this can guard against possible recurrence and malignant transformation.     

EXAMINATION OF DEVELOPMENTAL NEUROTOXICITY BY THE USE OF TISSUE CULTURE MODEL SYSTEMS

1. The rotation-mediated three-dimensional reaggregate culture system is uniquely suited for studies on developmental neurotoxicity. In this system, it is possible to reconstruct central neuronal pathways and follow their development. 2. Exposure to drugs of abuse including methamphetamine and methylenedioxyamphetamine or the appetite suppressant, fenfluramine, reduces monoamines in the cultures in a dose-dependent manner and interrupts normal monoaminergic development. 3. While the monoaminergic neurones may attain normal rates of development following drug removal, the affected neurones are not capable of overcoming the drug-induced insults and a deficiency in monoamines persists throughout development. 4. In addition, the production of immortalized monoclonal hybrid cells obtained by fusion of fetal mesencephalic neurones with a neuroblastoma has yielded cell lines expressing a dopaminergic phenotype. 5. Such cells have been useful in establishing the relationship of neurotoxicity to cell lineage and can serve as models for the study of the cellular and molecular mechanisms of neurotoxicity.     

Pharmacokinetics of oral alminoprofen (Minalfen) in elderly patients with rheumatoid arthritis and spondylosis deformans]

The pharmacokinetics of oral Alminoprofen, a nonsteroidal anti-inflammatory drug, were studied in five elderly patients with rheumatoid arthritis and spondylosis deformans after 200 mg (three times a day) repeated dose for 5 days. The pharmacokinetic parameters after oral administration of Alminoprofen were analyzed by the one-compartment open model method. The maximum plasma concentrations (Cmax) were 16.1 +/- 2.5 micrograms/ml, after dosing on day 1, 25.2 +/- 1.6 micrograms/ml on day 3 and 21.6 +/- 2.7 micrograms/ml on day 5. The maximum time (Tmax) were about 2 hours after the medication in al cases. The area under the curve in drug concentration in plasma versus time (AUC) were 58.5 +/- 6.3 micrograms hr/ml on day 1, 58.5 +/- 3.1 micrograms hr/ml on day 3 and 58.1 +/- 8.5 micrograms hr/ml on day 5. The biological half-lives (t1/2) were 2.45 +/- 0.35, 2.09 +/- 0.82 and 2.49 +/- 0.63 hours, after dosing on day 1, day 3 and day 5, respectively. The analysis of moment in pharmacokinetics revealed that the mean residence time (MRT) on day 1, day 3 and day 5 observed were 2.31 +/- 0.03, 2.15 +/- 0.09 and 2.15 +/- 0.07 hours, respectively. The variance residence times (VRT) observed were 0.95 +/- 0.05 hour2 on day 1, 0.88 +/- 0.09 hour2 on day 3 and 1.06 +/- 0.07 hour2 on day 5. The ratios of accumulation calculated were 1.16 +/- 0.05 in both the morning medication on day 3 day 5, and it therefore appears that the steady-state equilibrium is established within 3 days after commencement of dosage.(ABSTRACT TRUNCATED AT 250 WORDS)