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Biomedical subjects

K Schuster

Publications and source records attributed to K Schuster.

79 records · Page 5Linked to original sources

In vitro analysis of HIV- and non-HIV-infected monocytes/macrophages from healthy subjects and patients with malignant tumours.

Phenotype and release of IL1 alpha, IL6 and TNF alpha were examined in monocytes derived from 14 healthy donors and 24 tumour patients in a long-term culture using immunohistochemical, RNA in situ hybridization and ELISA techniques. After stimulation with LPS and IFN-gamma, blood monocytes and resulting macrophages showed an overall decrease in cytokine release from the 6th to the 48th day of culture, both with and without HIV infection. HIV infection provided a strong stimulus for IL6 production and a weak stimulus for IL1 alpha production, whereas TNF alpha release decreased after HIV infection. Non-HIV-infected monocytes/macrophages from patients with malignancies showed significantly reduced cytokine production after stimulation, in comparison with monocytes/macrophages from healthy subjects. In vitro HIV infection of monocytes from tumour patients caused severe depression of cytokine production during the whole time of observation. In all experiments a parallel was observed between the extent of cytokine release and the presence of young/early inflammatory macrophages as identified by the antibody MAC387/27E10 in situ. In contrast, cytokine expression assessed semiquantitatively by immunohistochemical staining in situ showed discordant development, since it increased during long-term culture, while supernatant concentrations of cytokines declined. Simultaneously, significant cytokine RNA levels could be found in macrophages from the 6th to the 24th day of culture, as detected by in situ hybridization. After 48 days of culture, no more cytokine RNA was detectable, while macrophages continued to exhibit distinct immunohistochemical positivity for cytokine antibodies. From these results, it is concluded that macrophages kept in culture for a long period become inhibited in their secretion. HIV has an ambivalent effect on cytokine production in Mo/Mac, resulting in an increase in IL6 and IL1 as well as a decrease in TNF alpha production. Mo/Mac of non-HIV-infected tumour patients show significantly reduced cytokine production in comparison with Mo/Mac from healthy subjects. The sum of the HIV infection in vitro and the tumour burden results in a dramatic reduction in cytokine release in Mo/Mac. This finding may provide a possible explanation for the specific aggressive behaviour of non-Hodgkin's lymphoma and Hodgkin's disease in AIDS.

Antigens, Differentiation↗

Cytokine expression of HIV-infected monocytes/macrophages at the single-cell level.

Monocytes of healthy donors were infected with HIV1 in vitro: 14-21 days after infection 50-70% of the cells produced p24 HIV1 antigen as detected with anti-p24 immunostaining; infected cultures showed enhanced secretion of interleukin-6 (IL6), interleukin-8 (IL8) and tumour necrosis factor alpha (TNF-alpha). The expression of cytokines on the single-cell level was further analysed by in situ hybridization using nonradioactive digoxigenin for detection. HIV1 (p24+) -producing cells were compared with non-HIV (p24-) -producing cells. All morphological subtypes of macrophages showed HIV production; no difference in cytokine expression was observed. Immunocytochemistry of HIV-infected and uninfected cultures also showed no difference in the pattern of IL1-beta, IL6, IL8 and TNF-alpha protein expression in the cells.

Cytokines↗

The role of laparoscopy in the preoperative staging of pancreatic carcinoma.

Between January 1990 and December 1995, a total of 398 patients underwent laparotomy for pancreatic or periampullary carcinoma at the Surgical Clinic of Mannheim. The tumor was located in the pancreatic head in 290 patients (72.9%), in the body of the pancreas in 42 patients (10.6%), and in the pancreatic tail in 19 patients (4.7%). Forty-seven patients (11.8%) presented with periampullary carcinoma. The preoperative diagnostic workup included abdominal ultrasound, CT scan, endoscopic retrograde cholangiopancreatography, and angiography. One hundred seventy-two patients (43.2%) underwent a tumor resection, 150 (37.7%) had a palliative bypass operation, and 76 (19.1%) underwent only an exploratory laparotomy. Preoperative diagnosis had predicted unresectability in 66 (87%) of the patients who underwent exploratory laparotomy. In 76 patients the intraoperative findings showed an unresectable tumor, which was located in the head of the pancreas in 54 cases (71%), in the body of the pancreas in 17 (22.4%), in the tail region in four (5.3%), and in the periampullary region in one (1.3%). Local signs of unresectability were found in 47 patients (62%) and peritoneal or hepatic metastases in 29 (28.2%). Given that local inoperability can be reliably assessed only at laparotomy, this leaves just 29 (7%) of 398 patients who did not require palliation and whose signs of unresectability could possibly have been discovered by means of the laparoscopic approach. Laparoscopy (including laparoscopic ultrasound) should be used selectively in patients considered probably unresectable who do not require a palliative procedure immediately before the planned operation.

Ampulla of Vater↗

Effects of methylphenidate on attentional function after traumatic brain injury. A randomized, placebo-controlled trial.

Attention deficits after traumatic brain injury (TBI) are common and disabling. Many pharmacologic agents have been used to ameliorate attention deficits, and considerable interest has focused on methylphenidate (MP) because of its documented efficacy in attention deficit disorder. However, clinical studies of MP in subjects with TBI have yielded mixed results. We examined the effects of MP on attentional function in individuals with TBI referred specifically for attentional assessment and treatment. Subjects were studied in a double-blind, placebo-controlled, repeated crossover design, using five different tasks designed to measure various facets of attentional function. MP produced a significant improvement in the speed of mental processing. Orienting to distractions, most aspects of sustained attention, and measures of motor speed were unaffected. These results suggest that MP may be a useful treatment in TBI but is primarily useful for symptoms that can be attributed to slowed mental processing.

Adolescent↗