Search PubMed⌕ Search

Biomedical subjects

C Pohl

Publications and source records attributed to C Pohl.

At least 37 records · Page 2Linked to original sources
PubMed1997

Specific activation of resting T cells against tumour cells by bispecific antibodies and CD28-mediated costimulation is accompanied by Th1 differentiation and recruitment of MHC-independent cytotoxicity.

Specific activation of resting lymphocytes for tumour targeting can be achieved by bispecific monoclonal antibodies (bi-MoAbs) with specificity for tumour antigens and T cell-activating antigens in combination with a costimulatory anti-CD28 antibody. In this study we focus on the immunomodulatory function of an anti-CD3/CA19-9 bi-MoAb in combination with a costimulatory anti-CD28 antibody which may result not only in antigen-specific, T cell-mediated tumour cell lysis but also in recruitment of other cellular effector functions. In combination with costimulatory anti-CD28 antibodies, resting peripheral lymphocytes could be activated specifically to secrete high amounts of Th1 cytokines (IL-2, interferon-gamma (IFN-gamma)) characterizing a cellular immune response. In contrast, no IL-4 and only low amounts of IL-10 could be detected. Furthermore, bi-MoAb-mediated CA19-9-specific activation of T cells was accompanied by recruitment of MHC- and CA19-9-independent cytotoxicity, as was determined by lysis of different CA19-9-cell lines. This MHC-independent cytotxicity was mediated at least in part by activated natural killer (NK) cells, as depletion of CD16+ NK cells resulted in substantial decrease of cytotoxicity against CA19-9- targets. Our results indicate that specific activation of resting T cells with CD3-associated bi-MoAbs in combination with an anti-CD28 antibody leads to a Th1 differentiation pathway and is accompanied by recruitment of MHC-independent lymphokine-activated killer (LAK) cell cytotoxicity which can possibly be directed against a heterogeneous tumour.

Antibodies, Bispecific↗
PubMed1997

T cell targeting of TAG72+ tumor cells by a chimeric receptor with antibody-like specificity for a carbohydrate epitope.

BACKGROUND & AIMS: Chimeric receptors with specificity for defined tumor antigens are valuable tools for targeting cytolytic T cells specifically to tumor cells. The aim of this study, for the situation of gastrointestinal cancer, was to investigate the generation of a chimeric T cell receptor that specifically binds the tumor antigen TAG72 (CA72-4) and transmits a signal for cellular activation. METHODS: A single-chain antibody (scFv) was derived from the monoclonal anti-TAG72 antibody B72.3 by phage display techniques (B72.3-scFv) and fused to the signaling unit of the Fc epsilon-RI receptor gamma chain, resulting in a chimeric signaling receptor, B72.3-scFv-gamma. RESULTS: The B72.3-scFv and the chimeric B72.3-scFv-gamma receptor bound specifically to the TAG72 antigen. After transfection, T cells expressing the chimeric B72.3-scFv-gamma specifically recognized TAG72 positive cells. Cross-linking of the chimeric receptor with antigen resulted in interleukin 2 release and cytolytic activity against TAG72 positive tumor cells in vitro. CONCLUSIONS: T cells equipped with the chimeric anti-TAG72 receptor can be specifically activated to target and lyse TAG72 positive gastrointestinal tumor cells.

Animals↗
PubMed1997

A prospective evaluation of the diagnostic work-up before laparoscopic cholecystectomy.

BACKGROUND AND STUDY AIMS: A prerequisite for successful laparoscopic cholecystectomy is the exclusion of potential risks such as cholangiolithiasis or anatomical malformations. As there is no general agreement regarding the appropriate preoperative diagnostic work-up, a comparative study of different diagnostic methods was carried out. PATIENTS AND METHODS: In 180 consecutive patients admitted to a community hospital for cholecystectomy due to symptomatic cholecystolithiasis, a prospective comparison was carried out of the diagnostic accuracy of patient history, physical examination, laboratory tests, upper gastrointestinal endoscopy, intravenous cholangiography, ultrasonography, and endoscopic retrograde cholangiopancreatography (ERCP). RESULTS: Measurement of the diameter of the common bile duct was found to be a reliable method as a single noninvasive parameter for diagnosing cholangiolithiasis (sensitivity 100%, specificity 93%), with good predictive power (positive predictive value 0.7, negative predictive value 1.0). The best accuracy achieved noninvasively and without sonography was with a combination of positive patient history and gamma-glutamyl transferase findings (sensitivity 58%, specificity 84%, positive predictive value 0.37, negative predictive value 0.93). ERCP detected additional cholangiolithiasis in 19 of 139 patients (13.7%) and anatomical malformations in three patients. In all 19 patients, the bile ducts were cleared of stones endoscopically within 24 hours, prior to laparoscopic cholecystectomy. Among the 163 patients primarily assigned to laparoscopic cholecystectomy, the protocol diagnostic work-up, including ERCP, allocated three patients (1.8%) to open surgery. Conversion from laparoscopic cholecystectomy to open cholecystectomy occurred in a further two of 158 patients (1.3%). CONCLUSIONS: These results show that routine ultrasonography prior to laparoscopic cholecystectomy can be recommended in order to determine the diameter of the common bile duct. In patients with a ductal diameter of more than 6 mm, ERCP should be performed. Laparoscopic cholecystectomy can be carried out within 24 hours after ERCP and papillotomy.

Adolescent↗
PubMed1997

Specific activation of resting T cells against CA19-9+ tumor cells by an anti-CD3/CA19-9 bispecific antibody in combination with a costimulatory anti-CD28 antibody.

Specific activation of resting lymphocytes for tumor targeting can be achieved by bispecific monoclonal antibodies (bi-mAb) with specificity for tumor antigens and T-cell-activating antigens, respectively, in combination with a costimulatory anti-CD28 antibody. We describe the generation and function of a bi-mAb with specificity for CD3 and for the tumor antigen CA19-9. The bi-mAb OKT3/NSI19-9 was generated by somatic fusion of two hybridoma lines secreting antibodies against CA19-9 and CD3, respectively. A hybrid/hybridoma was established, and its bi-mAb was characterized. In combination with a costimulatory anti-CD28 mAb resting peripheral lymphocytes could be activated specifically with T-cell proliferation and secretion of high amounts of interferon-gamma. On specific T-cell activation, bi-mAb OKT3/NSI19-9 could also redirect the cytotoxic effects of these T cells toward CA19-9+ tumor cells in vitro. Our results indicate that specific activation of resting T cells with bi-mAb OKT3/NSI19-9 in combination with an anti-CD28 mAb can activate resting T cells specifically and leads to antigen-dependent bi-mAb-mediated cytotoxicity against CA19-9+ target cells. This approach may offer new perspectives for the specific immunotherapy of CA19-9+ tumors.

Antibodies, Bispecific↗
PubMed1996

Eliminating amino acid and peptide interference in high-performance anion-exchange pulsed amperometric detection glycoprotein monosaccharide analysis.

The monosaccharide content of a glycoprotein is often determined by acid hydrolysis at elevated temperature and subsequent high pH chromatography of the released, underivatized monosaccharides on pellicular anion-exchange resin (HPAE) using pulsed amperometric detection (PAD). We have found that for glycoproteins with low levels of glycosylation, monosaccharide quantitation can be compromised by amino acids fouling the working electrode surface. Specifically, lysine elutes on the CarboPac PA1 column just prior to galactosamine, whereas remaining amino acids and most peptides elute after the monosaccharides and do not interfere with monosaccharide quantification. A direct comparison of PAD vs Abs215 detection of lysine using the CarboPac PA1 column as the separator reveals that lysine does not cleanly come off the working electrode. The monosaccharide response inhibition caused by lysine could be corrected by the posthydrolysis addition of a rhamnose internal standard and the determination of "correction factors." We have developed a guard column with an altered selectivity for amino acids which, when used with a new separator, causes lysine to elute after the monosaccharides and also causes hydrophobic amino acids to elute further after the monosaccharides. Together the new separator and guard columns solve the lysine fouling problem, reduce sample-related baseline noise, and reduce the magnitude of correction factors.

Amino Acids↗
PubMed1996

18F-fluorodeoxyglucose-PET and 99mTc-bicisate-SPECT in Creutzfeldt-Jakob disease.

In a patient with the occipitoparietal form of Creutzfeldt-Jakob disease (CJD) (Heidenhain type) positron emission tomography (PET) demonstrated decreased glucose utilization in the occipital lobes and adjacent cortical regions. Single photon emission computed tomography (SPECT) with 99mTc-bicisate showed a "coupled" decrease in blood flow in identical cortical areas in this patient. In contrast, magnetic resonance imaging (MRI) was normal. In the early stage of CJD, when still no major morphological abnormalities can be observed, functional imaging is useful for differential diagnosis, particularly to exclude other causes of dementia or pathological EEG patterns.

Aged↗
PubMed1996

ALS.

The cause of ALS is not known but there are four main hypotheses about its etiology. First, an excess of extracellular glutamate in the CNS of patients with ALS resulting from a defect in glutamate reuptake may have excitotoxic effects on motor neurons. Clinical trials suggest the antiglutamate agent riluzole improves survival of patients with the disease. Second, ALS may be an autoimmune disease, but immunologically-based treatments have been unsuccessful. The third hypothesis is that ALS results from a lack of neurotrophic growth factors. Preliminary results from clinical trials indicate recombinant human insulin-like growth factor I offers therapeutic promise. Finally, familial ALS is sometimes linked to a gene encoding a Cu/Zn-binding superoxide dismutase; the mutations in ALS are thought to result in gain of function of dismutase activity. The involvement of superoxide dismutase in sporadic ALS is unclear.

Amyotrophic Lateral Sclerosis↗
PubMed1996

[Chronic diarrhea--rational diagnosis and therapy].

Chronic diarrhea, defined by frequent bowel movements with decreased stool consistency lasting for longer than 3 weeks represents a major problem in gastroenterology. In addition to the very frequent functional disturbances of irritable bowel syndrome a wide variety of infectious, drug-induced, alimentary, metabolic, hormonal and organic causes requires a thorough evaluation of this symptom. To reach diagnosis an algorithm applying a wide array of diagnostic procedures based on the results of thorough anamnesis, physical examination and stool visit should be followed. In addition to alleviation of symptoms, reconstitution and prevention of nutrional deficits (volume, electrolytes, trace elements, vitamines, calories) therapeutic approaches should eliminate underlying causes whenever possible. Symptomatic relief is provided by substances inhibiting secretion and motility as the opiatagonist Loperamid or anticholinergics. Substitution of vitamins, trace elements, calories, enzymes or bile salts should be adapted to the individual needs. Elimination of a cause of chronic diarrhea is generally provided be anti-infectious therapy, other causes however (e.g. sprue by the elimination of gliadin from diet) may be treated effectively as well.

Chronic Disease↗
PubMed1996

[Primary biliary cirrhosis--cellular mechanisms and role of enterobacterial antigens].

The nature of primary biliary cirrhosis (PBC) is still unknown. In this study the diagnostic value of the expression of MHC proteins and adhesion molecules in bile duct epithelia, the different amount of inflammatory cells around the bile ductules and the evidence of enterobacterial antigens were tested in liver tissue of patients with PBC, chronic hepatitis B and C, autoimmune hepatitis and cellular or ductopenic liver transplant rejection. There was a significant difference according MHC and adhesion molecules between PBC and rejections at the one and the cases of chronic hepatitis at the other hand. According to inflammatory infiltrate there was no difference. The enterobacterial antigen lipid-A was found more often in centrolobular hepatocytes of PBC/PSC cases but not in the portal bile duct region. The possible pathogenetic role of enterobacterial antigens in the disease are discussed.

Antigens, Bacterial↗
PubMed1995

Relations between verbal and nonverbal memory performance: evidence of confounding effects particularly in patients with right temporal lobe epilepsy.

Confounding left hemisphere verbalization strategies can be suggested as being a major problem in the evaluation of the assumed involvement of right temporo-limbic structures in "nonverbal" visual/figural memory processing. We addressed this issue by evaluating the easily-verbalized Benton-visual-retention-test in 60 patients with either left (LTLE) or right temporal lobe epilepsy (RTLE) and 30 healthy controls. We formally estimated the informational (verbal) content of each item which hypothetically would be needed to solely retain the item from verbal memory. The results indicated confounding of verbal learning and figural memory only in the presence of right temporal lobe dysfunctions. Selective visual/figural learning deficits in RTLE patients became obvious when the verbal load of the figural material exceeded their verbal learning capacity. Instead of excluding verbalization by the use of abstract figural items, its inclusion provides a possibility to control compensatory strategies which overshadow the presence of visual/figural memory deficits.

Adult↗
PubMed1994

Cure of xenografted human tumors by bispecific monoclonal antibodies and human T cells.

Tumor immunotherapy should increase both the number of T cells that kill the tumor and the likelihood that those cells are activated at the tumor site. Bispecific monoclonal antibodies (Bi-mAbs) were designed that bound to a Hodgkin's tumor-associated antigen (CD30) on the tumor and to either CD3 or CD28 on the T cell. Immunodeficient mice were cured of established human tumors when mice were treated with both the CD3-CD30 and the CD28-CD30 Bi-mAbs and then given human peripheral blood lymphocytes that had been incubated with the CD3-CD30 Bi-mAb and cells that expressed CD30. The enrichment of human T cells within the tumor and the fact that established tumors can be cured may indicate in situ activation of both the T cell receptor and the costimulatory pathway.

Animals↗
PubMed1994

Scintigraphic localization of the bleeding site of a large retroperitoneal hematoma following renal angioplasty.

Although the scintigraphic detection of a few soft tissue hematomas have been reported, these usually have been serendipitous discoveries that were small and self-limited. The authors report a case of a large, rapidly expanding retroperitoneal hematoma that occurred following a left renal angioplasty. While the hematoma was initially detected by CT imaging, the precise source of the bleeding could not be definitively localized. Scintigraphy with labeled RBC cells, however, identified the left femoral artery puncture site as the bleeding source, which was subsequently surgically repaired.

Aged↗
PubMed1994

Contrast-enhanced MR imaging of the breast: comparison of two different doses of gadopentetate dimeglumine.

PURPOSE: To optimize detection and diagnosis of breast lesions with contrast-enhanced magnetic resonance (MR) imaging. MATERIALS AND METHODS: A three-dimensional fast low-angle shot pulse sequence was used for a group comparison consisting of 76 high-dose (0.16 mmol gadopentetate dimeglumine per kilogram of body weight) and 76 low-dose (0.1 mmol/kg) examinations. Intraindividual comparisons were possible in a subgroup of 20 patients. RESULTS: Enhancement with the high dose was about 1.5 times higher for benign and malignant tissues. With the lower dose, no false-positive findings could be avoided and definition of a threshold that excluded false-negative findings was problematic. Conspicuity of malignant lesions was much improved with the higher dose (a good to excellent rating in 81% vs 26% with the lower dose). Three small foci were visible only with the higher dose. CONCLUSION: The higher dose of contrast material allowed much better results. Dose comparison studies are also recommended for other techniques.

Breast↗
PubMed1994

Mimicry of the Hodgkin-associated IRAC antigen by an anti-idiotype network: potential use in active immunotherapy of Hodgkin's lymphoma.

The murine monoclonal antibody anti-IRac, defining a surface-antigen structure (MW 70 kDa) on Hodgkin-Reed-Sternberg and interdigitating reticulum cells, was used to generate a cascade of anti-idiotypic antibodies as well as a cellular immunity against Hodgkin-Reed-Sternberg cells in syngeneic BALB/c-mice. The anti-idiotypic antibody monoclonal antibody 4B4 demonstrated characteristics of an "internal image" or network antibody (Ab2 beta). Ab2 beta 4B4 bound specifically to anti-IRac and inhibited anti-IRac-binding to antigen-bearing cells effectively. 4B4 induced an IRac-specific humoral polyclonal immune response in BALB/c-mice and New Zealand white rabbits as judged by Flow cytometric and histochemical analysis. Moreover, BALB/c-mice immunized with 4B4 showed statistically significant (p > 0.01) delayed-type hypersensitivity reaction against IRac-expressing Hodgkin cell-lines. Ab2 beta 4B4 induced in syngeneic BALB/c mice a monoclonal anti-anti-idiotypic antibody (Ab3) termed 3G10, which mimicked the specificities of Ab1 anti-IRac and thus confirms the internal image nature of Ab2 beta 4B4. The anti-idiotype-induced tumor cell specific T- and B-cell mediated immune response even across species barriers via the Hodgkin related IRac-antigen may play an important part in active specific immunotherapy of Hodgkin's disease.

Animals↗
PubMed1993

A CD16/CD30 bispecific monoclonal antibody induces lysis of Hodgkin's cells by unstimulated natural killer cells in vitro and in vivo.

In order to target NK cells against the Hodgkin's-derived cell line L540, we developed bispecific monoclonal antibodies (Bi-MAbs) by somatic hybridization of the 2 mouse hybridoma cell line HRS-3 and A9 which produce monoclonal antibodies (MAbs) with reactivity against the Hodgkin and Reed-Sternberg cell-associated CD30 antigen and the CD16 antigen (Fc gamma III receptor), respectively. The CD16 MAb-producing cell line A9 was selected as a partner for HRS-3 because of its efficiency in inducing lysis of the A9 hybridoma cells by resting NK cells. The hybrid hybridoma cell line HRS-3/A9 produced the supernatant with the strongest bispecific reactivity and was repeatedly subcloned and used for ascites production. Crude supernatant and purified HRS-3/A9 Bi-MAb triggered specific lysis of the CD30+ Hodgkin's-derived cell line L540, but not of the CD30- cell line HPB-ALL by unstimulated peripheral-blood lymphocytes and NK-cell-enriched populations. Moreover, treatment of SCID mice bearing heterotransplanted human Hodgkin's tumors with HRS-3/A9 and human peripheral blood lymphocytes induced specific complete tumor regression in 10/10 animals. We thus report successful tumor treatment in an in vivo model using NK-cell-associated Bi-MAbs and show that the Bi-MAb HRS-3/A9 is an efficient promoter of the anti-tumor effects of NK cells in vitro and in vivo.

Animals↗