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Biomedical subjects

C Pohl

Publications and source records attributed to C Pohl.

At least 73 records · Page 4Linked to original sources
PubMed1992

Soluble CD8, CD25 and CD30 antigens as prognostic markers in patients with untreated Hodgkin's lymphoma.

In a search for serum markers with prognostic value and specificity for disease activity in Hodgkin's lymphoma, we evaluated the clinical significance of soluble suppressor/cytotoxic T-cell antigen (sCD8), soluble interleukin-2 receptor (sCD25) and soluble Hodgkin's associated antigen (sCD30) levels in the serum of 90 patients with untreated Hodgkin's lymphoma (HD). HD patients in advanced stages had significantly higher sCD8 and sCD25 levels than normal controls. The rate of detectable sCD30, which was absent in healthy controls, depended on stage and histological subtype, and was 22% for the entire group. Low sCD25 levels (< 1000 U/ml) predicted an excellent prognosis (100% event-free survival), while patients with high sCD8 levels (> 750 U/ml) or the demonstration of sCD30 had a poor outcome. Therefore, all three markers have prognostic significance. However, only sCD30 correlated strictly with disease activity and seems to be of value for the follow-up of patients in remission.

Adolescent↗
PubMed1992

Experimental therapy in Hodgkin's disease.

Hodgkin/Reed-Sternberg (H-RS) cells express lymphoid activation markers like CD25 and CD30 which are present only on a small minority of normal cells. Currently, most experimental approaches in Hodgkin's lymphoma are aimed at targeting H-RS cells via monoclonal antibodies against CD25 and CD30: immunotoxins constructed by linking the antibody moiety chemically to deglycosylated ricin A-chain destroy up to 60% of small H-RS tumors in mice. The most potent immunotoxin is currently being scaled up for clinical trials. Other experimental strategies use bispecific constructs that, after binding to the cell surface of H-RS cells, convert prodrugs into their toxic counterparts, or employ monoclonal antibodies for active immunotherapy.

Alkaline Phosphatase↗
PubMed1992

Respiratory syncytial virus infections in pediatric liver transplant recipients.

Respiratory syncytial virus (RSV) is the most important cause of lower respiratory tract infection in infants and young children. The charts of 17 children found to have RSV among 493 children who underwent liver transplantation between February 1985 and February 1991 were reviewed. The median age at diagnosis was 20 months. Median time of diagnosis was 24 days after transplantation. Thirteen patients developed nosocomial infections while convalescing from their transplant. Common symptoms included tachypnea, cough, fever, and congestion. Acute radiographic changes were seen in 12 patients. Two deaths were associated with progressive pulmonary disease and occurred in children with infection early in the postoperative period who were intubated before the onset of symptoms. RSV in children after liver transplantation has a clinical spectrum similar to that in normal children. Early onset of infection (less than 20 days) after transplantation and preexisting lung disease may predict more severe disease.

Child↗
PubMed1992

T4+ cell numbers are correlated with plasma glutamate and cystine levels: association of hyperglutamataemia with immunodeficiency in diseases with different aetiologies.

Human immunodeficiency virus type 1 (HIV-1) seropositive individuals suffer from a depletion of T4+ T cells and have elevated plasma glutamate levels. Glutamate is also elevated in cancer patients, and several authors have shown that elevated extracellular glutamate levels inhibit competitively the membrane transport of cystine and cause a decrease of intracellular cystine. We, therefore, tested the hypothesis that high glutamate and/or low cystine levels may generally be associated with low lymphocyte reactivity or low T4+ counts. In three independent studies we tested (i) serum amino acid levels (AAL) versus T4+ counts in healthy individuals, (ii) plasma AAL versus lymphocyte responses in healthy individuals, and (iii) plasma AAL versus T4+ counts in HIV-1 seropositive individuals. When the individuals in each study were divided into four subgroups as defined by median glutamate and cystine levels, the results showed that persons with a combination of low glutamate and high cystine level (LGHC subgroups) had the highest mean T4+ count or highest lymphocyte reactivity. Moreover, the LGHC subgroup in a study of lung cancer patients had a much longer mean survival time than the other three subgroups. In HIV-1 infected patients, hyperglutamataemia is associated with hypocystinaemia and hypocysteinaemia. Azidodeoxythymidine (AZT) treated HIV patients had, on average, lower glutamate levels than patients without AZT.(ABSTRACT TRUNCATED AT 250 WORDS)

CD4-Positive T-Lymphocytes↗
PubMed1992

Bone marrow involvement in non-Hodgkin's lymphoma: increased diagnostic sensitivity by combination of immunocytology, cytomorphology and trephine histology.

Diagnostic results from cytomorphology and immunocytology of aspirated bone marrow (BM) were compared with the findings from standard trephine histology of 100 adult patients with non-leukaemic non-Hodgkin's lymphomas (NHL) in a retrospective study. Immunocytological investigations were performed by the immunoenzymatic APAAP-technique on BM smears monoclonal antibodies against CD19, Cd3, CD10 or TdT antigens and determination of positive cells in relation to total BM leucocytes. Corresponding results were obtained for trephine histology and for the combination of cytomorphology and immunocytology in 93/100 cases. Four cases with BM involvement by trephine histology were missed by the combination of immunocytology and cytomorphology. In turn, three cases negative by trephine histology, were found to be positive by the combination of immunocytology and cytomorphology. Immunocytochemistry considerably increased the number of true positive detected BM-infiltrations by cytomorphology in low grade B-cell lymphoma from 58% to 97%. For the diagnosis of BM involvement in high-grade NHL cytomorphology of the aspirate was of equal sensitivity to the biopsy and was always confirmed by immunocytology. The high diagnostic sensitivity of immunocytology was mainly due to high B-cell counts in BM involved by B-cell lymphoma (means = 38%, s = 23) in contrast to low B-cell counts in BM not involved by NHL (means = 4.5%, s = 3.8). We conclude from our data that immunocytology in addition to standard cytomorphology improves diagnostic sensitivity in the detection of BM involvement by NHL.

Adolescent↗
PubMed1992

The clinical significance of cytokines and soluble forms of membrane-derived activation antigens in the serum of patients with Hodgkin's disease.

In a search for specific serum markers with prognostic impact in Hodgkin's Disease (HD), we evaluated the clinical significance of several cytokines (IL-1 beta, IL-2, IL-3, IL-6, G-CSF, GM-CSF, TNF-alpha) and soluble forms of membrane-derived antigens (sCD4, sCD8, sCD23, sCD25, sCD30) in the serum of patients with untreated HD. Elevations of three groups of serum factors were observed: Firstly, elevations of the hematopoietic cytokines GM-CSF (detected in 39%), IL-6 (57%) and IL-3 (13%), which occurred simultaneously in the majority of the cases; secondly, simultaneous elevations of the inflammatory cytokines TNF-alpha and IL-1 beta (detected in 7%); and finally, elevations of membrane-derived activation antigens sCD8, sCD25, and sCD30. While the cytokine levels did not correlate with other obvious parameters, the membrane-derived activation antigens sCD8, sCD25 and sCD30 were associated with a poor prognosis. Only sCD30 correlated with disease activity and holds promise for the follow-up of patients in remission. Further investigations of these parameters at the cellular level might help to elucidate the enigmatic biology of HD.

Antigens, CD↗
PubMed1992

[Acute abdominal pain--standardized findings as diagnostic support. Results of a prospective multicenter intervention study and testing of a computer-assisted diagnosis system].

Despite powerful diagnostic tools (e.g. ultrasound, special laboratory investigations), the diagnosis of acute abdominal pain is still a considerable problem. Several studies in the UK have shown that the diagnostic accuracy can be improved by structured and standardized history taking and clinical examination and by computer-aided diagnosis. In the framework of a concerted action of the European Community we have conducted a prospective multicenter interventional trial comparing two consecutive phases: a) a baseline phase in clinical routine without additional intervention, b) a test phase with structured and standardized history and clinical examination (questionnaire, documentation programme). In addition, a computer-aided diagnostic system developed in the UK was applied to the cases in the test phase. Outcome criteria were the diagnostic accuracy of the initial and the final examiner, the perforated appendix rate, the negative appendectomy rate, the negative laparotomy rate and the rates of diagnostic errors with missing indication to operation and of delayed urgent operations. No differences could be found between the phases with respect to the outcome criteria. In the baseline phase (test phase) diagnostic accuracy was 59% (59%), diagnostic accuracy after investigation (senior examiner) was 77% (78%), perforated appendix rate was 11% (16%), negative appendectomy rate was 13% (15%), negative laparotomy rate was 7% (8%), the rate of missed urgent indications to operation was 1.1% (1.9%) and the rate of delayed urgent operations was 3.4% (2.4%). Major differences between the centers were recorded. Computer-aided diagnosis resulted in a diagnostic accuracy of 51%. The introduction of structured and standardized history taking and clinical examination has not brought any improvement of the good results in clinical routine. It is doubtful, whether existing systems of computer-aided diagnosis are able to significantly decrease the still remaining error rate of 20%.

Abdomen, Acute↗
PubMed1992

Increased levels of circulating cytokines in patients with untreated Hodgkin's disease.

Expression of several cytokines has been demonstrated in Hodgkin and Reed-Sternberg (H&RS) cells in vitro and in vivo. In order to determine whether interleukin-1 beta (IL-1 beta), IL-3, IL-6, GM-CSF, G-CSF, and TNF-alpha are elevated in Hodgkin's disease (HD), we tested the sera of untreated patients with HD by means of sensitive sandwich ELISAs. GM-CSF was detected in 22/56 patients (39%; range 40-140 pg/ml), IL-3 in 5/40 (13%; range 13-26 pg/ml), and IL-6 in 32/56 patients (57%; range 12-332 pg/ml). TNF-alpha and IL-1 beta were detected in only 3/43 patients (7%; range: TNF-alpha: 36-66 pg/ml; IL-1 beta: 389-1505 pg/ml) and G-CSF not at all. All patients with measurable IL-3 levels had both elevated IL-6 and GM-CSF levels, and the majority of patients with elevated IL-6 also had elevated GM-CSF levels and vice versa. In contrast, the 3/40 patients with both measurable IL-beta and TNF-alpha did not have elevated IL-3, IL-6, or GM-CSF levels. Cytokine levels were independent of stage or the presence of B-symptoms, and there was no correlation with any other clinical or laboratory parameter. Elevations of the respective cytokines might be a means to maintain normal blood cell counts in the respective patients with HD.

Adolescent↗
PubMed1991

[Immunoproliferative disease of the small intestine. A rare differential diagnosis of Crohn's disease].

For 2 years a 39-year-old Turkish man had had abdominal pain as well as weight loss of more than 10 kg over 4 months, associated with a raised ESR (33 mm/h) and recurrent gastrointestinal bleedings which endoscopy revealed to have been caused by a marked erosive duodenitis. Biopsies from the duodenum and terminal ileum demonstrated lymphoplasmocytic infiltration of the entire small intestine in the sense of immunoproliferative small intestinal disease (IPSID). By immunohistochemistry the lymphoplasmacellular infiltrate showed polyclonal expression of IgA without IgA increase in serum, urine and duodenal juice. The patient was treated with tetracycline (500 mg twice daily) for one year. The symptoms and histological lesions were much improved after 4 months. One year after diagnosis he was symptom-free.

Adult↗
PubMed1991

[Malignant lymphoma associated with HIV infection].

The course of disease in 119 HIV-infected patients (117 men, 2 women; median age 38.5 years) with malignant tumours other than Kaposi's sarcoma was analyzed in a multi-centre retrospective study. This was conducted to obtain initial information concerning the incidence, clinical features and results of therapy in HIV-associated neoplasms, especially malignant lymphomas. The most frequent tumour was malignant non-Hodgkin's lymphoma (98 patients, 82.5%), seven patients had Hodgkin's disease, five had solid tumours, four a polyclonal lymphoproliferative syndrome, three an acute lymphocytic leukaemia, and two had other lymphoproliferative diseases. 58% of the non-Hodgkin's lymphomas occurred in patients with marked immunodeficiency, 85% were high grade malignancies and 47% had primary extranodal disease. 56% of primary nodal lymphomas also had visceral spread (Stage IV). Lymphoblastic non-Hodgkin's lymphoma was more common in patients with favourable immunological status, presented less frequently with primary extranodal disease, was diagnosed earlier than other non-Hodgkin's lymphomas, and appeared to carry a better prognosis. 78 out of the 98 patients with non-Hodgkin's lymphoma had been treated, 66 with cytotoxics. The median survival time was 6 months. Longer remission periods, of at least 12 months, were seen in ten of the 78 patients (13%). Despite the overall poor prognosis and the pre-existing immune defect, palliative (chemo-)therapeutic measures are both justified and promising, and may also result in life-prolonging remissions.

Adult↗
PubMed1991

Clinical significance of soluble CD30 antigen in the sera of patients with untreated Hodgkin's disease.

The soluble form of the CD30 antigen (sCD30), an 88-kd glycoprotein that is released by Hodgkin's-derived cell lines in vitro, can be detected in patients with Hodgkin's lymphoma, adult (HTLV-1+) T-cell leukemia, rare cases of non-Hodgkin's lymphoma, and acute infectious mononucleosis (anti-EBV-IgM+). In a prospective study of 90 consecutive untreated patients with newly diagnosed Hodgkin's disease who were treated according to the protocols of the German Hodgkin Study group, 22% had detectable levels of sCD30 in their serum. sCD30 was only detected in patients with B symptoms (20 of 44 or 45%), and maximum sCD30 levels (88 U/mL) were found in stage IVB. Of 87 patients evaluable for response, sCD30+ patients had significantly lower rates of complete remission (9 of 20 or 45% v 60 of 67 or 90%; P less than .001) and higher rates of progressive disease (9 of 20 or 45% v 6 of 67 or 9%; P less than .001) than CD30+ patients. Similarly, freedom from treatment failure curves were significantly worse for CD30+ patients (P = .0003). sCD30 disappeared after successful treatment, but increased in patients with progressive disease. It was never detected in patients in complete remission or in healthy controls. We conclude that sCD30 is a valuable marker for disease activity and has prognostic significance in Hodgkin's disease.

Adolescent↗
PubMed1991

Visual learning deficits in nonresected patients with right temporal lobe epilepsy.

A visual learning test Diagnostikum für Zerebralschäden (DCS) was revised and applied to three matched patient groups defined by interictal and ictal EEG findings: 24 patients with left temporal lobe epilepsy (LTE), 19 patients with right temporal lobe epilepsy (RTE) and 34 patients with a bitemporal epileptic involvement (BTE). Fifty seven healthy subjects served as controls. Performance on a measure of sustained attention and visual construction was also assessed. Results were as follows: (1) In contrast to controls and LTE patients, patients with right temporal epileptic involvement (RTE/BTE) showed a significantly reduced immediate recall as well as a reduced learning capacity and mean learning performance. (2) Patients made significantly more errors than controls, with RTE patients exhibiting the most visuo-spatial errors. (3) RTE/BTE patients additionally showed impaired performances on visuo-construction, but when visual construction scores were used as covariate, they did not diminish the strong group effects upon learning. (4) Attentional deficits were independent from memory deficits and rather reflected the bitemporal extention of epilepsy. As a conclusion, the data suggest an impairment of visual-spatial consolidation processes in patients with right temporal lobe epilepsy.

Adult↗
PubMed1990

Specific activation of the prodrug mitomycin phosphate by a bispecific anti-CD30/anti-alkaline phosphatase monoclonal antibody.

The bispecific monoclonal antibody (Bi-MAb) HRS-3/AP-1 was developed by somatic hybridization of the 2 mouse hybridoma cell lines HRS-3 and AP-1, which produce monoclonal antibodies with reactivity against the Hodgkin's- and Reed-Sternberg cell-associated CD30 antigen and alkaline phosphatase, respectively. After an active incubation with alkaline phosphatase, respectively. After an active incubation with alkaline phosphatase, purified whole immunoglobulin molecules and F(ab')2 fragments of the Bi-MAb were equally effective in converting a relatively noncytotoxic prodrug, mitomycin phosphate (MOP), into mitomycin alcohol, which was 100 times more toxic to the Hodgkin's- and Reed-Sternberg cell line L540 (CD30+) than MOP. The cytotoxic activity of MOP was unaffected when the cells were pretreated with either the Bi-MAb or the enzyme alone. The Bi-MAb HRS-3/AP-1 did not bind to HPB-ALL cells (CD30-) and was not able to activate MOP on these cells. In cocultivation experiments with HPB-ALL and L540 cells, the activation of MOP by the Bi-MAb HRS-3/AP-1 and alkaline phosphatase led to considerable cytotoxicity against the antigen-negative bystander cells. Thus, this immunotherapeutic approach might be effective in tumors in which not all the tumor cells express the respective tumor antigen.

Alkaline Phosphatase↗
PubMed1990

Detection of a soluble form of the CD30 antigen in sera of patients with lymphoma, adult T-cell leukemia and infectious mononucleosis.

Using a sandwich enzyme-linked immunosorbent assay (ELISA) we were able to detect a soluble form of the CD30 antigen (CD30s) in the supernatant of cell lines expressing membrane-bound CD30 and in T and B cells after transformation with human T-cell leukemia virus (HTLV-I) and Epstein-Barr-Virus (EBV). While CD30s was not found in 250 healthy controls, it was detected in the sera of patients with Hodgkin's disease (23/100), anaplastic large-cell (6/9), angioimmunoblastic (2/2) and one unclassified high-grade non-Hodgkin's lymphoma (NHL), as well as in 18/20 patients with acute adult T-cell leukemia (ATL, HTLV-I-positive). It was absent in a large number of patients with other high-grade NHL, all low-grade NHLs, acute or chronic leukemias and solid tumors. The only non-malignant disease with detectable levels of CD30s was infectious mononucleosis (9/10). The membrane-bound form of CD30 has a molecular weight of 120 kDa. Western blot analysis revealed that CD30s in the serum of patients has a molecular weight of 88 kDa, identical to the antigen released by cell lines in vitro. CD30s disappeared in all originally positive cases after successful treatment and reappeared in relapsing patients. Thus, CD30s may be useful as a specific marker for disease activity of certain types of lymphoma and ATL.

Adult↗
PubMed1990

Alpha-fetoprotein in the woodchuck model of hepadnavirus infection and disease: immunochemical analysis of woodchuck alpha-fetoprotein and measurement in serum by quantitative monoclonal radioimmunoassay.

Woodchuck hepatitis virus infection of the eastern woodchuck represents a useful model for the study of hepatitis B virus infection and disease in humans, including hepatocellular carcinoma. In man, hepatocellular carcinoma is frequently detected and monitored using assays for serum alpha-fetoprotein. To study the relationship between alpha-fetoprotein and woodchuck hepatitis virus-induced hepatocellular carcinoma in the woodchuck model, we produced a monoclonal antibody to woodchuck alpha-fetoprotein and used biophysical and immunochemical methods to demonstrate its specificity and affinity (7 x 10(8) L/mol) for woodchuck alpha-fetoprotein. A competition radioimmunoassay was then developed and standardized for measuring serum alpha-fetoprotein concentrations. In the radioimmunoassay system, woodchuck alpha-fetoprotein was detected between 20 ng/ml (20% to 25% inhibition) and 8,500 ng/ml (97% to 98% inhibition). Elevated serum alpha-fetoprotein concentrations (450 to 452,000 ng/ml) were measured in 21 of 23 woodchucks in the advanced stages of woodchuck hepatitis virus-induced hepatocellular carcinoma. Serum alpha-fetoprotein was elevated above normal (greater than or equal to 450 ng/ml) as early as 3 to 11 mo before terminal hepatocellular carcinoma in 11 of 16 of the woodchuck hepatitis virus-carrier woodchucks. In a pilot study, serum alpha-fetoprotein became markedly elevated above normal in woodchuck hepatitis virus-carrier woodchucks that developed hepatocellular carcinoma but not in serologically recovered or uninfected woodchucks (i.e., without hepatocellular carcinoma). Thus, alpha-fetoprotein may provide a useful noninvasive marker in the woodchuck model for detecting and monitoring woodchuck hepatitis virus-induced hepatocellular carcinoma from earlier stages.

Animals↗