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Biomedical subjects

A Knuth

Publications and source records attributed to A Knuth.

125 records · Page 7Linked to original sources
PubMed1985

Biliary adenocarcinoma. Characterisation of three new human tumor cell lines.

Three human cell lines from adenocarcinomas of the extrahepatic biliary tract were established in permanent tissue culture. Mz-ChA-1 and Mz-ChA-2 were cultured from mechanically dissociated gallbladder adenocarcinoma metastases and SK-ChA-1 was grown from malignant ascites of a patient with primary adenocarcinoma of the extrahepatic biliary tree. Cell doubling times in tissue culture are 3-4 days for Mz-ChA-1 and approximately 2 days for Mz-ChA-2 and SK-ChA-1. All three tumour cell lines were successfully transplanted to nude mice, inducing progressive tumour growth. Histologically, nude mouse tumours resembled the original adenocarcinomas. In vitro formation of gland-like structures were regularly seen in Mz-ChA-1 and Mz-ChA-2 but only occasionally in SK-ChA-1. All three cell lines formed contacts through interdigitating processes with desmosomes and junctional complexes. On scanning electron microscopy, an abundance of microvilli was seen at the cell surfaces. Chromosome analyses of all three tumour cell lines showed a wide range of numerical abnormalities and presence of marker chromosomes. Mz-ChA-1 appears to be highly differentiated with cells producing mucus. Mz-ChA-2 synthesizes components of complement C2, C3 and C5, while Mz-ChA-1 and SK-ChA-1 produce only C3 in detectable quantities. In addition, Mz-ChA-2 supernatants are positive for ferritin and alpha 1-fetoprotein, but not CEA; while Mz-ChA-1 and SK-ChA-1 produce only CEA. Supernatants of all three cell lines are positive for N-acetyl neuraminic acid (NANA), phosphohexoisomerase (PHI) and LDH, and negative for alpha 2-macroglobulin, alpha 1-anti-trypsin, gamma-GT, AP, coeruloplasmin, haptoglobin and albumin. A high cloning efficiency renders these new tumour cell lines suitable for continued studies on clonal heterogeneity in malignant tumours. The establishment of these cell lines in tissue culture facilitates further studies on the biology of upper gastrointestinal tract cancer in man.

Adenocarcinoma↗
PubMed1985

Immunohistochemical localization of ganglioside GD3 in human malignant melanoma, epithelial tumors, and normal tissues.

The specific tissue distribution of melanoma-associated ganglioside II3-alpha-N-acetylneuraminosyl-alpha 2----8-N-acetylneuraminosyllactosylceramide (GD3) was studied on 175 cryopreserved, unfixed human tissue sections with R-24 mouse monoclonal antibody by indirect immunoperoxidase staining. A striking specificity of monoclonal antibody R-24 for malignant melanoma tissues was established. Ganglioside GD3 was detected in all 21 tissue sections of 21 patients with primary melanoma and in all 37 probes of 24 patients with metastatic malignant melanoma. The majority of tumor cells in the samples of primary malignant melanoma expressed GD3; however, GD3 expression was more heterogeneous in samples of metastatic lesions even in different metastases of the same patient. Of 11 nevi, 9 reacted with monoclonal antibody R-24, while melanocytes in the basal layer of normal skin stained only weakly and irregularly. None of the 32 normal and 12 fetal human tissue types were R-24 positive, but a strong cytoplasmic staining was observed with single cells in the dermis and in the interstitial tissue of the gastrointestinal tract, in the interlobular septa of the thymus, and in other distinct locations. Only two malignant carcinoid tumors of 38 nonmelanomatous tumors tested reacted with monoclonal antibody R-24.

Adult↗
PubMed1984

Target level blocking of T-cell cytotoxicity for human malignant melanoma by monoclonal antibodies.

Cytotoxic T lymphocytes (CTL) for autologous malignant melanoma in culture of a patient AV were induced by restimulation of PBL (peripheral blood leukocytes) with AV melanoma cells in vitro and subcultured in interleukin 2 (IL-2) conditioned media. Monoclonal antibodies detecting six antigenic systems on melanoma cell surfaces were tested for blocking activity on the effector function of subcultured cytolytic T lymphocytes for autologous melanoma cells. The monoclonal antibodies R24 (gamma 3), specific for the GD3 disialoganglioside on melanoma cell surfaces and I24 (gamma M), detecting a similar antigenic determinant, blocked autologous T lymphocytotoxicity for malignant melanoma cells on the target level. The effector function of alloantigen activated cytolytic T lymphocytes generated by coculture of allogeneic PBL with Epstein-Barr virus (EBV) transformed AV B lymphocytes, was blocked by monoclonal antibody R24 when tested against AV melanoma targets, but not when tested against AV B lymphocyte targets. It is concluded that blocking by mAb R24 occurs in this system as a nonspecific effect, unrelated to the specific target antigen recognition by cytotoxic T lymphocytes. Steric hindrance or antibody induced membrane changes may account for the blocking effect of monoclonal antibody R24.

Antibodies, Monoclonal↗
PubMed1984

T-cell-mediated cytotoxicity against autologous malignant melanoma: analysis with interleukin 2-dependent T-cell cultures.

The cytotoxic reactivity of lymphocytes for autologous melanoma cells was studied in a group of 13 melanoma patients. No cytotoxicity was observed with lymphocytes freshly isolated from peripheral blood or with lymphocytes cocultured for 7 days with autologous melanoma cells. Growth of lymphocytes previously sensitized with autologous melanoma in vitro in interleukin 2 (IL-2)-containing medium, however, resulted in cytotoxic reactivity for autologous melanoma in 7/13 patients. The reactivity of IL-2-dependent lymphocytes for autologous melanoma was particularly striking in one patient (A.V.) who has had an unexpectedly favorable clinical course and, because of their consistently high reactivity, AV lymphocytes were selected for detailed specificity analysis. After 2-3 weeks in culture in IL-2-containing medium, AV lymphocytes were cytolytic for autologous melanoma cells but not autologous Epstein-Barr virus-transformed B cells, autologous fibroblasts, or allogeneic tumor targets. Specificity of autologous melanoma reactivity was confirmed by competitive inhibition assays. The IL-2-dependent AV lymphocytes formed rosettes with sheep erythrocytes and expressed OKT 3 and Ia antigens. After longer periods of culture, AV lymphocytes were found to react with a wider range of target cells, and repeated attempts to isolate cultures with restricted reactivity to autologous melanoma by resensitization with autologous melanoma and limiting-dilution techniques were unsuccessful. The restricted reactivity of early cultures could be preserved, however, in frozen storage, but shifted again toward broader reactivity after several weeks in culture. The recognition of cytotoxic T cells with initial restricted reactivity for autologous melanoma suggests reinvestigation of the question of specific cellular immunity to human cancer.

Cells, Cultured↗
PubMed1984

Melanoma antibodies: specificity and interaction with melanoma and cytotoxic T-cells.

Six antigenic systems on melanoma cell surfaces have been defined by monoclonal antibodies. The disialoganglioside GD3, detected by mAb R-24, was found to be strongly expressed on most melanoma cell surfaces, but weakly on normal melanocytes and some astrocytomas as determined by serological methods. Epithelial cell types, fibroblasts and cells of hematopoietic origin did not react. Frozen sections of primary and metastatic malignant melanoma stained positive in 60/62 cases by immunofluorescence and immunoperoxidase. In vitro studies with seven antibodies to seven melanoma cell surface antigens revealed blocking of melanoma cell growth by monoclonal anti-GD3-antibody R-24 only. GD3-expression varies greatly in human malignant melanoma cells. Six melanoma cell lines, expressing high levels of GD3 on the cell surface, as determined by quantitative absorption studies, showed growth inhibition in the presence of R-24 antibody. Four melanoma cell lines, however, with low GD3-expression and seven GD3-negative non-melanoma cells types remained unaffected by mAbR-24. In addition, this monoclonal anti-GD3-antibody efficiently blocked T-cell cytotoxicity for autologous malignant melanoma cells in culture. Cytotoxicity of autologous cloned T-lymphocytes, cytotoxic for the autologous melanoma cell line and crossreactive with a hypernephroma line was specifically blocked by mAbR-24 on the level of the GD3-expressing target. In an ongoing phase I clinical study, the toxicity of mAbR-24 was evaluated. So far two patients tolerated antibody infusions without adverse reactions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Inhibition of human melanoma cell growth in vitro by monoclonal anti-GD3-ganglioside antibody.

Malignant melanoma cell growth in vitro was blocked by the monoclonal antibody R-24, which detects the disialoganglioside GD3 on melanoma cells. GD3 expression varies greatly in cultured human malignant melanoma cells. The level of ganglioside GD3 was measured by quantitative absorption tests. In our observations, six melanoma cell lines expressing high levels of GD3 on the cell surface showed growth inhibition and rounding up in the presence of R-24 antibody. Four melanoma cell lines with low levels of GD3 and seven nonmelanoma cell lines with no detectable GD3 remained unchanged in morphology and continued to grow. The data presented indicate that complement is not involved in the growth inhibition observed here. Because ganglioside GD3 was detected in all 16 tissue specimens of primary and metastatic human malignant melanoma examined by immunofluorescence tests, the possible relevance of this finding in vivo is discussed.

Antibodies, Monoclonal↗
PubMed1983

Natural antibodies in human sera directed against blood-group-related determinants expressed on colon cancer cells.

Sera from 136 normal males and 33 members of families at high risk for colon cancer were tested for reactivity with six colon cancer cell lines by the protein A-mixed hemadsorption assay. Ninety-one sera had antibodies to colon cancer cell line HT-29. In 89 cases the antibodies were absorbed by human A and B erythrocytes or sheep erythrocytes. Antibodies in the remaining two sera, which were from sisters in the high-risk group, were not absorbed by red cells but could be absorbed by tumor cells expressing A or B blood-group determinants. Their reactivity was inhibited by some soluble blood-group glycoproteins. One serum (No. 4) was inhibited by A-active glycoproteins from human saliva and ovarian cyst fluids and from porcine mucosa, as well as by a polysaccharide derived from gastric cancer; it has an anti-A-like specificity. The other serum (No. 6) was inhibited by A and B glycoproteins, by a blood group precursor glycoprotein and by the same gastric cancer polysaccharide; it seems to have a wider specificity directed towards both A- and B-like structures. It is not known what caused production of these antibodies but it may be significant that they occurred in members of a family at high risk for developing colon cancer.

Absorption↗
PubMed1983

[Candida meningitis. Case report].

Subacute meningitis caused by Candida albicans was confirmed by culture and immunoserologically in a 19-year-old girl. Combined administration of amphotericin B and flucytosine only slowly affected the course of the disease despite impressive improvement in clinical symptoms. Pleocytosis (1000/mm3) in cerebrospinal fluid persisted. Falling Candida antibody titre in serum and CSF, however, pointed to an improvement in the acute infection. Treatment had to be discontinued after 42 days because of side-effects such as rigor, fever and polyuria with low concentration. Under serial clinical observations with occasional CSF punctures complete cure occurred with normal CSF findings. There was an additional and unusual neurological-otological condition of intermittent inner-ear deafness, left more than right, before treatment. Recording of early auditory evoked potentials pointed to an involvement of the cranial nerves as part of the inflammatory process.

Adolescent↗
PubMed1983

Chromosome abnormality in a human TCGF-dependent T-lymphocyte culture generated against autologous melanoma cells in vitro.

Six T-cell growth promoting factor (TCGF)-dependent T-cell cultures and phytohemagglutinin-stimulated peripheral blood lymphocytes from a patient with metatastic malignant melanoma were karyotyped. Three of the TCGF-dependent cultures were noncloned, started after in vitro sensitization against autologous malignant melanoma cells in tissue culture. A fourth was a subculture of one of these. The two remaining T-cell cultures were generated by in vitro sensitization of the same individual's lymphocytes against allogeneic Epstein-Barr virus-transformed B-cell lines. One of the cultures (AV7) and its subculture (AV/LDP39) showed a 17q+ anomaly in 100% of metaphases studied. All other TCGF-dependent T-cell cultures and fresh blood lymphocytes had normal karyotypes. The possible mode of origin of the abnormality and its significance are discussed.

Adult↗
PubMed1982

An in vitro model for the study of human parathyroid gland tissue: single cell suspensions and monolayer cultures.

An in vitro model for studies of parathyroid physiology is described using single cell suspensions and adherent monolayer cultures of human parathyroid tissue. The isolated cells were viable and maintained functional properties tested by calcium and magnesium sensitivity. Parathyroid hormone (PTH) secretion could be suppressed by rising calcium and magnesium concentrations. The secretory behaviour of the cells was not altered by cultivation or cryopreservation. The morphological integrity of the individual cells after mechanical and enzymatic preparation was confirmed by light and electron microscopy.

Adenoma↗
PubMed1979

Hemoglobin Moabit: alpha 86 (F7) Leu leads to Arg: a new unstable abnormal hemoglobin.

A new alpha chain abnormal hemoglobin variant was found in a Turkish patient with a mild Heinz body hemolytic anemia and splenomegaly. The substitution alpha 86 Leu leads to Arg, which is next to the heme binding proximal histidine, is responsible for a marked instability of the molecule. The oxygen affinity of the erythrocytes was found to be slightly decreased.

Adult↗
PubMed1977

[Myelomonocytic leukemia: clinical, cytological, and cytogenetic studies of acute, subacute, and chronic forms (author's transl)].

44 patients suffering from myelomonocytic leukemia (MML) have been observed over the last four years. They have been subclassified in acute myelomonocytic and acute monoblastic leukemias (AMML, n = 12; AMoL, n = 10), subacute myelomonocytic leukemias (SMML, n = 13), and chronic myelomonocytic leukemias (CMML, n = 9) on the basis of bone marrow cytology(blast and promonocyte counts, maturation of granulopoesis) and cytochemical findings (peroxydase and unspecific esterase reaction). This subclassification has been proved to be of prognostic relevance by its good correlation with the mean survival times (AMML : 4.5 months, AMoL : 2.4 months, SMML : 8 months, CMML : 18 months). The acute forms have been treated in general with combined cytostatic chemotherapy, whereas SMML and CMML have been treated this way only in case of progression to an acute phase. These progressions to an AMML have been observed more often and earlier in subacute forms than in chronic forms. The diagnosis of SMML and CMML is supported by the finding of sea-blue histiocytes in the bone marrow, increased lysozyme levels in serum and urine and by the absence of the Philadelphia-Chromosome.

Acute Disease↗
PubMedDate not supplied

Hepatocellular carcinoma after thorotrast exposure: establishment of a new cell line (Mz-Hep-1).

A human hepatoma cell line, associated with thorotrast exposure, from an hepatitis B marker-negative patient was established as a permanent cell line (Mz-Hep-1) in tissue culture. Histology of the primary tumor, as well as phase contrast, transmission and scanning electron microscopy of the cultured cells showed typical characteristics of liver cells. Mz-Hep-1 cells secreted complement components (C2, C3, C4), carcinoembryonic antigen, lactate dehydrogenase, chymotrypsin, haptoglobin and retinol-binding protein and expressed HLA-, transferrin-, blood group B-related determinants and complement component C5 and carcinoembryonic antigen on their cell surface. Mz-Hep-1 cells represent the first human hepatoma cell line, which is strongly associated with a carcinogen.

Angiography↗
PubMedDate not supplied

Second-line treatment with high-dose 5-fluorouracil and folinic acid in advanced colorectal cancer refractory to standard-dose 5-fluorouracil treatment.

Results with second-line treatment of advanced colorectal cancer are poor. Preliminary phase I/II results suggest encouraging response rates to high-dose 5-fluorouracil (FU) (2,600 mg/m2) combined with folinic acid (FA) in pretreated patients with advanced colorectal cancer. To determine the significance of weekly high-dose FU/FA in colorectal cancer refractory to weekly standard doses of FU/FA, a phase II study was initiated. 69 patients with metastatic colorectal cancer refractory to first-line weekly standard-dose FU/FA were treated with weekly high-dose FU 2,600 mg/m2 combined with FA 500 mg/m2 as a 2-hour infusion prior to FU application. Pretreatment was highly homogenous and consisted of weekly FU 500 mg/m2 combined with FA 500 mg/m2 or FA 20 mg/m2 or the pure stereoisomer of FA (6S-FA) 250 mg/m2. At the time of disease progression under first-line therapy, patients were transferred to high-dose FU/FA within 4 weeks. Treatment was continued until tumor progression under therapy was documented. Of the 69 evaluable patients, 17 (24.6%) achieved partial response (PR), 42 (60.9%) had no change (NC) and 10 (14.5%) had progressive disease under therapy. The median duration of PR was 7 months, the median time to progression of NC was 4 months. Median survival of all patients was 9 months, of patients with PR, 11.5 months. 33/38 patients with tumor-related pain experienced impressive relief under therapy. Prognostic factors for a beneficial outcome were complete response/PR under first-line therapy, a small number of metastatic sites and a good Karnofsky performance status. Moderate toxicity was observed, and the pattern of toxic events and severity did not differ from standard-dose FU regimens.(ABSTRACT TRUNCATED AT 250 WORDS)

Antimetabolites, Antineoplastic↗
PubMedDate not supplied

Combination of 5-fluorouracil, adriamycin, ifosfamide and cisplatin in metastatic adult soft tissue sarcoma: results of a phase II study.

Treatment results of advanced soft tissue sarcomas are still suboptimal. To evaluate the clinical effects of a combination therapy (FADIP) with Adriamycin (ADM), ifosfamide (IFO), cisplatin (DDP) plus continuous infusion of 5-fluorouracil (FU) as a synergistic factor for alkylating agents, a phase II study was initiated in patients with advanced soft tissue sarcomas of different histological subtypes. Fifty-six previously untreated patients with advanced soft tissue sarcomas of different histological subtypes (24 females, 31 males, median age 51.3 years, median Karnofsky performance status 80%) were included in this study. Treatment consisted of ADM 50 mg/m2 i.v. on day 1, IFO 4,000 mg/m2 i.v. on day 1, mesna 800 mg/m2 i.v. 3 x with 8-hour intervals on day 1 starting with IFO administration, FU 500 mg/m2 i.v. as 24-hour infusion on days 1 + 2, DDP 100 mg/m2 i.v. on day 2. This regimen was repeated every 4 weeks for at least 2 cycles. Major WHO grade III/IV hematological toxicity was observed in 35/56 patients. One toxic death due to severe neutropenia and fungal pneumonia occurred. Granulocyte colony-stimulating factor was administered in 8/35 neutropenic patients. Time to recovery was significantly reduced and no infectious complication was observed. WHO grade III/IV toxic diarrhea was observed in 8 patients requiring intravenous fluid replacement. WHO grade III/IV nausea occurred in 11 patients, 9/11 responded to symptomatic treatment with ondansetron alone. The overall response rate was 30.3%. The median duration of response (complete/partial response, CR/PR) was 18.1 months, the median progression-free interval was 4.5 months. The median survival time of all patients was 11.8 months, and 18.1 months in responding patients (CR/PR). Tumor-related pain was effectively reduced in 15/31 patients under treatment. FADIP produces comparable response rates to other standard treatment regimens in soft tissue sarcomas. Prolonged duration of response and median survival may be due to the use of continuous infusion of FU as a synergistic factor to alkylating agents. Granulocyte colony-stimulating factor is effective in reducing the otherwise observed high rate of WHO grade III/IV hematological toxicity with severe neutropenia.

Antineoplastic Combined Chemotherapy Protocols↗