Search PubMed⌕ Search

Biomedical subjects

K Krohn

Publications and source records attributed to K Krohn.

At least 127 records · Page 7Linked to original sources
PubMed1989

Hexestrol-linked cytotoxic agents: synthesis and binding affinity for estrogen receptors.

With the erythro-hexestrol derivative 2 as the starting material, a variety of cytotoxic linked hexestrol (HEX) compounds were prepared including the HEX-N-lost derivative 36, the HEX-(chloroethyl)nitrosourea 38, the HEX-cyclophosphamide 44, and the HEX-epoxide 68. Relative binding affinity to estradiol receptors were in the magnitude of 1%, similar to that of comparable diethylstilbestrol compounds. HEX derivatives with long polyether spacers (64, 65, 70, 71) showed no significant decrease in binding affinity in contrast to derivatives with other bulky side chains.

Antineoplastic Agents↗
PubMed1989

Isolate- and group-specific immune responses to the envelope protein of human immunodeficiency virus induced by a live recombinant vaccinia virus in macaques.

The immune responses produced by four macaques inoculated intradermally with a recombinant vaccinia virus that expresses the envelope gene of human immunodeficiency virus (HIV) were analyzed. Antibody capable of immunoprecipitating the glycosylated envelope protein precursor gp160 was detected in all animals within 3 weeks after the primary intradermal vaccination. The level of antibody was increased following a booster inoculation, and the sera from three of the four animals were then capable of immunoprecipitating gp120. Sera from two of the macaques with anti-gp120 antibody were able to prevent syncytium formation mediated by the parent HIV but not that induced by an unrelated HIV isolate. The fusion-inhibiting antibody was directed toward the highly variable central portion of the gp120 molecule since the effect was abrogated by incubation with PB1. The latter is a recombinant protein produced in Escherichia coli containing amino acids 295-474, a major neutralizing epitope. Sera from the three macaques with anti-gp120 neutralized HIV infectivity in an isolate-specific manner. The serum with highest neutralizing activity was also best at inhibiting syncytium formation. In contrast to the isolate-specific nature of the neutralizing antibody, T lymphocytes from immunized animals proliferated in response to divergent HIV isolates as well as to purified gp120. These studies provide baseline immunologic information for further development of recombinant vaccinia virus vectors.

Animals↗
PubMed1989

No evidence for true HTLV-I or HIV-1 antibodies in Finnish Lapps.

Previous seroepidemiologic studies have suggested that in addition to certain subtropical and tropical parts of the world, human T cell leukemia virus type I (HTLV-I) may be endemic in the arctic regions, too. We studied 111 sera collected from original inhabitants of Finnish Lapland with ELISA and Western blot analysis for antibodies to HTLV-I and human immunodeficiency virus type 1 (HIV-1). No true positive sera for either virus were found in the confirmatory Western blot assays, albeit 6 and 2%, respectively, were positive in the screening ELISA assays. Despite the small sample size this survey does not support the hypothesis that HTLV-I would be endemic in the Arctic.

Arctic Regions↗
PubMed1989

T-cell response towards HIV in infected individuals with and without zidovudine therapy, and in HIV-exposed sexual partners.

HIV-specific T-cell response in HIV-infected individuals at different stages of the disease and during zidovudine therapy was studied using HIV and HIV-envelope derived native and recombinant proteins as antigens. Neither antibody-negative at-risk individuals nor HIV-infected individuals responded to HIV or its envelope-derived proteins, even though they responded to a recall antigen, purified protein derivative of tuberculin (PPD). However, five out of 14 antibody- and antigen-negative sexual partners of known HIV-positive men did respond to HIV, native gp 120 and recombinant envelope and core proteins. Some AIDS-related complex (ARC) and AIDS patients treated with zidovudine also showed a low T-cell response which diminished along with clinical deterioration. A synthetic peptide representing one of the major T-cell epitopes in HIV envelope, frequently recognized by immunized and infected primates, gave only marginal stimulation in man. Our findings suggest that HIV infection in man results in a T-helper cell anergy directed against viral proteins. The response observed in the antibody- and antigen-negative sexual partners and in some of the zidovudine-treated patients implies that at least some epitopes on HIV envelope are immunogenic in man.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Effects of pyocyanine, a phenazine dye from Pseudomonas aeruginosa, on oxidative burst and bacterial killing in human neutrophils.

The effects of pyocyanine (phenazinium, 1-hydroxy-5-methyl-hydroxide, inner salt) on oxidative burst in human polymorphonuclear leukocytes were studied by several different approaches. In a cell- and enzyme-free system, pyocyanine oxidized NADPH. The reduced pyocyanine could be measured by its reaction with ferricytochrome c. It was shown by this assay that resting as well as phorbol myristate acetate- or zymosan-stimulated granulocytes reduced pyocyanine. The effect was independent of mitochondria, as cytoplasts were similarly active. Measurement of the hexose monophosphate shunt in intact granulocytes in the presence of pyocyanine indicated a concentration-dependent activation of the shunt without the generation of O2-, suggesting that pyocyanine oxidizes NADPH to NADP+ when it enters granulocytes. Intracellular NADPH in granulocytes was indeed lowered by almost 40% after incubation with pyocyanine. It is by this shuttling of reduction equivalents, leading to the partial depletion of NADPH, that pyocyanine affects the observed concentration-dependent partial inhibition of the phorbol myristate acetate- and zymosan-stimulated generation of O2-. A further consequence was that the intracellular killing of Staphylococcus aureus was also partially suppressed, particularly at higher loads of granulocytes with bacteria. Phagocytosis was not inhibited by pyocyanine concentrations as high as 500 microM. Pyocyanine did not affect the intracellular killing of Pseudomonas aeruginosa. The possible relevance of these findings to the course of mixed hospital infections in immunocompromised patients is discussed.

Blood Bactericidal Activity↗
PubMed1989

Challenge of chimpanzees (Pan troglodytes) immunized with human immunodeficiency virus envelope glycoprotein gp120.

The human immunodeficiency virus type 1 (HIV-1), the causative agent of acquired immunodeficiency syndrome, infects humans and chimpanzees. To determine the efficacy of immunization for preventing infection, chimpanzees were immunized with gp120 purified from human T-cell lymphotrophic virus type IIIB (HTLV-IIIB)-infected cell membranes and challenged with the homologous virus, HTLV-IIIB. A challenge stock of HTLV-IIIB was prepared by using unconcentrated HTLV-IIIB produced in H9 cells. The titer of the virus from this stock on human and chimpanzee peripheral blood mononuclear cells and in human lymphoid cell lines was determined; a cell culture infectivity of 10(4) was assigned. All chimpanzees inoculated intravenously with 40 cell culture infectious units or more became infected, as demonstrated by virus isolation and seroconversion. One of two chimpanzees inoculated with 4 cell culture infectious units became infected. Chimpanzees immunized with gp120 formulated in alum developed antibodies which precipitated gp120 and neutralized HTLV-IIIB. Peripheral blood mononuclear cells from gp120-vaccinated and HIV-infected animals showed a significantly greater response in proliferation assays with HIV proteins than did peripheral blood mononuclear cells from nonvaccinated and non-HIV-infected chimpanzees. Two of the gp120-alum-immunized chimpanzees were challenged with virus from the HTLV-IIIB stock. One animal received 400 cell culture infectious units, and one received 40 infectious units. Both animals became infected with HIV, indicating that the immune response elicited by immunization with gp120 formulated in alum was not effective in preventing infection with HIV-1.

Animals↗
PubMed1989

Proliferative T-cell response to HIV envelope glycoprotein in immunized and infected primates and human beings.

Human immunodeficiency virus (HIV)-specific helper T-cell response was studied in human subjects and nonhuman primates either infected with HIV or immunized with different HIV protein preparations. A strong group-specific T-cell response involving T-cell proliferation and lymphokine secretion was observed in immunized chimpanzees and rhesus monkeys as well as HIV-infected chimpanzees and gibbons. HIV-infected people demonstrated a low or no HIV-specific T-cell response. In contrast, five of 14 HIV antibody-negative sexual partners of HIV-infected men recognized one or more T-cell epitopes in the envelope glycoprotein of HIV.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Relation of parietal cell and thyroid antibodies to the state of gastric mucosa and basal serum gastrin levels during a 6-year follow up.

Two groups of volunteers (199 in total, 149 of whom were a random sample of an urban population) were examined twice, with a 6-year interval, for the occurrence of parietal cell antibody (PCA) and thyroid microsomal antibodies (TMA). The antibody findings were compared with the antral and fundal gastric mucosal state, and with the fasting serum gastrin-17 level. During the study period, two new PCA and four new TMA cases appeared. There were no significant changes in the state of gastric antral/fundal mucosa in relation to PCA and/or TMA persistence or appearance, as compared with the gastric mucosa changes in the whole random population sample. However, a good correlation was observed between PCA and basal serum gastrin elevation.

Adult↗
PubMed1988

In vitro cellular tropism of human B-lymphotropic virus (human herpesvirus-6).

We investigated the cellular tropism of human B-lymphotropic virus (HBLV) (also designated Human Herpesvirus-6) in vitro by infecting fresh MN cells from normal human adult peripheral blood, umbilical cord blood, bone marrow, tonsil, and thymus. Cultures from all the sources examined contained infectable cells, as shown by the appearance of characteristic enlarged, round-shaped, short-lived cells expressing HBLV-specific markers. Detailed immunological analysis demonstrated that the vast majority of these cells expressed T cell-associated antigens (i.e., CD7, CD5, CD2, CD4, and to a lesser extent, CD8). The CD3 antigen and the TCR-alpha/beta heterodimer were not detectable on the surface membrane, but were identified within the cytoplasm of HBLV-infected cells, by both immunofluorescence and radioimmunoprecipitation assay. A proportion of the HBLV-infected cell population also expressed the CD15 and class II MHC DR antigens. By means of immunoselection procedures it was possible to show that a consistent proportion of HBLV-infectable cells were contained within the CD3-depleted immature T cell population, while the depletion of CD2+ cells completely abrogated the infectability of the cultures. Northern blot analysis confirmed the T cell origin of HBLV-infected cells, demonstrating the expression of full size TCR-alpha and -beta chain mRNA. In addition to fresh T cells, HBLV was able to infect normal T lymphocytes expanded in vitro with IL-2 for greater than 30 d. These results indicate that HBLV is selectively T cell tropic in the course of the in vitro infection of normal mononuclear cells and may therefore be directly involved in the pathogenesis of T cell related hematological disorders. In particular, in light of the cytopathic effect exerted in vitro on CD4+ T lymphocytes, a possible role of HBLV in immune deficiency conditions should be considered.

Adult↗
PubMed1988

Elevated serum HMFG antigen levels in breast and ovarian cancer patients measured with a sandwich ELISA.

HMFG antigen is a tumour associated glycoprotein that has been immunohistochemically shown to be expressed by malignant cells in breast and ovarian and to a lesser degree in gastro-intestinal carcinomas. We have developed a non-isotopic sandwich ELISA for secretory HMFG antigen utilizing a polyclonal catcher and a tracer monoclonal antibody (MAb). 52/52 of healthy medical students (controls) had a serum value under 400 U/ml whereas 15/30 patients (50%) with evident ovarian cancer and 13/37 (35%) with advanced breast cancer had a value exceeding 400 U/ml. From other patients with malignant tumours 2/14 (14%) with endometrial carcinoma, 0/5 with cervical carcinoma, 0/5 with vulvar carcinoma, 1/33 with gastro-intestinal carcinoma, 0/4 with oesophageal carcinoma and 2/45 of patients with leukemia or lymphoma had an elevated serum HMFG value. Four cases of Crohn disease, 3 cases of ulcerative colitis and 2 cases of pelvic inflammatory disease all showed a serum value below 400 U/ml. Progression of ovarian cancer was accompanied by increasing serum HMFG antigen levels. The antigen detected by our assay is different from CA 125 but may be related with the tumour associated antigen CA 15-3.

Antigens↗
PubMed1988

Chromatographic and enzymatic effects on transfer factor-like activity from human leukocytes and porcine spleen dialysate.

1. The effect of dialysable transfer factor (TFd), derived from human leukocytes or porcine spleen cells, was measured using Listeria resistance in mice. 2. The molecular weight range of substance(s) containing TF-like activity is in the less than 3500 MW dialysis fraction on the basis of the capacity of peritoneal macrophages to produce superoxide anion (O2-). This biological activity is removed by heating at 56 degrees C. 3. After Sephadex G-10 chromatography of dialysates the significant activities are found in fractions III and IV of human leukocyte dialysate and in fractions of II and III of porcine spleen dialysate. 4. From enzymatic studies, most of the protective activity of both human leukocyte and porcine spleen dialysate is based on the action of small-molecular weight structures containing peptides and/or polynucleotides.

Animals↗
PubMed1988

Oral candidal infection as a sign of HIV infection in homosexual men.

The oral mucosae of 66 homosexual men were examined clinically and by means of cultivation to determine the presence of Candida infection. In addition, clinically detected mucosal changes were recorded and a biopsy specimen was obtained for the histopathologic classification. A total of forty one subjects (62%) showed clinical evidence of candidiasis. Fourteen (21%) of the sixty-six men were seropositive for human immunodeficiency virus (HIV). A total of thirteen of fourteen (93%) of the seropositive men and twenty-six of fifty-two (50%) of the HIV seronegative men had culture-confirmed oral candidiasis. In the latter group, oral candidiasis was clearly correlated to cigarette smoking. Clinical mucosal changes other than candidiasis were found in forty-five of the sixty-six subjects studied. The most frequent finding was trauma resulting from biting, which was usually localized on the cheek. Leukoplakia was found in twelve of sixty-six subjects, while cauliflower-like condylomas were present in 4 persons. The results emphasize the frequent occurrence of different oral lesions in subjects seropositive for HIV and in those at high risk for HIV infection. Oral examination in search for potential early manifestations of HIV infection in homosexual men is advocated.

Alcohol Drinking↗
PubMed1988

Oestrogen receptor content and cancer cell/stroma ratio in mammary carcinoma.

In a study of 86 human breast cancers the volume fraction of the neoplastic epithelium was estimated semiquantitatively and a significant association was found between the oestrogen receptor (ER) content and volume fraction of cancer cells of tumours (p less than 0.00001). Tumours with very low cellularity could thus be falsely ER negative. When quantitative ER concentration is used to predict the response of tumours to hormonal therapy the cellularity of tumours should be taken in consideration. The cellularity was not related to ER positivity. Although a correlation was seen between the contents of oestrogen and progesterone (PR) receptors, no correlation between PR content and volume fraction of the neoplastic epithelium was observed.

Breast Neoplasms↗
PubMed1988

Human milk fat globule antigen III D 5, steroid receptors and histopathologic parameters in breast cancer.

Immunohistochemical reactivity of mammary carcinomas with the monoclonal human milk fat globule (HMFG) antibody III D 5, and the estrogen receptor (ER) and progesterone receptor (PR) status were compared with the histopathology of primary breast cancer. The reactivity with III D 5 has earlier been shown to be associated with the estrogen receptor status of tumours and with a favourable prognosis. The reactivity of tumours with III D 5, as well as the presence of ER and PR correlated significantly with the histological features of differentiation; histological grade, nuclear grade, tumour necrosis and lymphoid infiltration. Reactivity with III D 5 correlated with all these parameters, while the presence of ER did not correlate with the nuclear grade and that of PR correlated only with the nuclear grade and the lymphoid infiltration of tumours. Reactivity of III D 5 may thus have prognostic and therapeutic implications in the management of breast cancer.

Adult↗
PubMed1988

Use of immunohistochemical staining panel for characterisation of ovarian neoplasms.

Eighty five ovarian epithelial and non-epithelial tumours were studied by peroxidase histochemical staining for their reactivity with six monoclonal human milk fat globule (HMFG) antibodies, peanut agglutinin (PNA) lectin, and a monoclonal cytokeratin antibody. HMFG IIIC12 and cytokeratin antibodies distinguished epithelial from non-epithelial tumours. The staining patterns of mucinous and serous tumours were essentially different from each other; poorly differentiated anaplastic carcinomas showed similar antigenic content to that of the serous cystadenocarcinomas. Furthermore, staining with PNA lectin and HMFG antibodies was useful in distinguishing clear cell carcinomas from other malignant epithelial tumours of the ovary.

Adenocarcinoma↗
PubMed1988

Neutralizing antibodies in relation to antibody-dependent cellular cytotoxicity-inducing antibodies against human immunodeficiency virus type I.

The presence of neutralizing antibodies against human immunodeficiency virus type 1 (HIV-1) was investigated in sera from 73 HIV-1 seropositive subjects at different clinical stages. Virus neutralization was measured as survival of MT-4 cells in a 6-7 day microassay. Sixty-three sera were also tested for antibodies inducing virus-specific antibody-dependent cellular cytotoxicity (ADCC). Neutralizing antibodies were found in 59% of sera tested, the positivity rate being 50% (9/17) in asymptomatic subjects, 67% (12/18) in patients with persistent generalized lymphadenopathy (PGL) and 54% (14/26) in AIDS patients (not significant differences). ADCC antibodies were present in 43% of the sera. Neutralizing antibodies and ADCC-inducing antibodies were found simultaneously in 35% (22/63) of the sera. Neutralizing antibodies alone were found in 22% (14/63) and ADCC antibodies alone in 6% (4/63) of the sera tested. Thirty-seven per cent (23/63) of the sera were negative for both types of antibodies, 62% of the sera with neutralizing antibodies also had ADCC inducing antibodies and 85% of the sera with ADCC antibodies had neutralizing antibodies. The titres of ADCC antibodies were higher than those of neutralizing antibodies. Thus, the presence of ADCC antibodies was related to the presence of neutralizing antibodies, but no correlation was found between the titres of these antibodies in sera positive for both activities.

AIDS-Related Complex↗