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Biomedical subjects

K Krohn

Publications and source records attributed to K Krohn.

At least 163 records · Page 9Linked to original sources

Diversity of clinical spectrum of HTLV-III infection.

In a prospective follow-up volunteer study lasting 4 to 16 months, 17 of 200 homosexual men living in Finland had antibodies to human T-lymphotrophic virus type III (HTLV-III). 1 man who initially had a low titre of HTLV-III antibodies became seronegative within 6 months without any symptoms developing, and a seronegative man became seropositive. 14 men had high titres of HTLV-III antibodies when they first joined the study and during the study titres rose in all other HTLV-III-positive men except those with AIDS. Initially 9 men were symptom-free, 3 had lymphadenopathy syndrome (LAS), 3 had AIDS-related complex (ARC), and 2 had AIDS. During follow-up LAS developed in 3 symptom-free HTLV-III positive men but none of those with LAS or ARC progressed to AIDS. Most HTLV-III-positive men, including those who were otherwise symptom-free, had mucocutaneous lesions generally associated with immune deficiency. Regardless of the symptoms, those with increasing HTLV-III antibody titres showed lowered T helper/T suppressor ratios, decreased numbers of T helper cells, and/or diminished responses to tuberculin antigen (PPD). These results suggest that the clinical spectrum of HTLV-III infection ranges from transient infection through chronic provirus state, asymptomatic virus producer state, LAS or ARC, and rarely full-blown AIDS. Cofactors probably determine the final outcome of infection in the individual.

Acquired Immunodeficiency Syndrome↗

A rapid and sensitive non-competitive avidin-biotin assay for lactoferrin.

We have developed an avidin-biotin assay for the detection of lactoferrin in human seminal plasma. We compared 5 modifications of this assay, and found the non-competitive avidin-biotin assay (NABA) to be the most sensitive. The detection limit of 3-step NABA was 0.2 or 0.1 ng lactoferrin/ml, depending whether avidin-biotin-peroxidase complex (ABC) or avidin-peroxidase was used. The intra-assay and inter-assay coefficients of variation for 3-step NABA were 6.2 and 8.5%, respectively. The lactoferrin levels of human seminal plasma samples measured by 3-step NABA and radioimmunoassay (RIA) showed good correlation (r = 0.96). The total performance time of 3-step NABA is flexible and the method can be modified for rapid (less than 1 h) or overnight assay according to need.

Avidin↗

Production of monoclonal antibodies against avidin.

Monoclonal antibodies of the IgG1 subclass were generated against chicken avidin. These antibodies were shown to be as sensitive as polyclonal antiserum in detecting avidin by radioimmunoassay (RIA) and enzyme linked immunosorbent assay (ELISA) methods. Furthermore, the monoclonal antibodies were considerably more specific. Our results with a monoclonal anti-avidin RIA support previous findings that in inflammatory conditions avidin is synthesized also in other organs than the oviduct, although in the liver a major part of the activity detected by polyclonal anti-avidin RIA or biotin-bentonite assay was not due to avidin.

Animals↗

Effect of human leukocyte and other tissue dialysates on Listeria resistance and phagocytosis in mice.

The effect of dialyzable transfer factor (TFd) on Listeria resistance was measured by survival studies and by assessing phagocytic capacity of peritoneal macrophages. Unfractionated dialysates from human leukocytes (DLE), bovine liver, porcine spleen and kidney as well as saline were injected i.p. into NMRI mice 72 h before the i.p. injection of 1-3 x 10(6) Listeria organisms. The results show that DLE, porcine spleen and bovine liver dialysate increased the LD50 5-20 times. Porcine kidney dialysate had no effect on the survival of the mice. After the fractionation of porcine spleen dialysate on Sephadex G-10 column, a significant activity was found in two fractions, II and IX. When active fractions were given together (II + IX) i.p. three days prior to the infection with listeria organisms, the survival of mice increased significantly, whereas no effect was seen when the fractions were given i.v. and the bacteria i.p. Also the treatment with active fractions increased significantly the phagocytic capacity of peritoneal macrophages. Taken together, our results suggest that the Listeria protective substances seem to operate via monocyte activation.

Animals↗

Cellular immunity in acne vulgaris during transfer factor treatment.

The effect of treatment with human dialyzable transfer factor was investigated on acne vulgaris patients in a double-blind study. About 1/3 of the patients improved clinically during the study period but there was no correlation between clinical improvement and transfer factor treatment. Prior to treatment parameters of cell-mediated immunity were significantly altered in the patients. These alterations normalized during the study in all patients irrespective of transfer factor treatment, possibly due to the immunostimulatory effect of repeated skin testing. The present results support previous findings that acne patients have slightly altered cell-mediated immunity, but the results further suggest that abnormalities are not significant in the pathogenesis of acne vulgaris.

Acne Vulgaris↗

Immune functions in homosexual men with antibodies to HTLV-III in Finland.

The occurrence of HTLV-III antibodies in a voluntary group of 175 homosexual men in a low risk AIDS area was studied, and the findings were correlated to clinical, virological, immunological and lifestyle parameters. Fifteen of 175 men had HTLV-III antibodies; two of these had AIDS, five had LAS and two had enlarged lymph nodes. In the HTLV-III antibody negative group, no signs of AIDS or pre-AIDS were seen during a 10 month follow-up. In HTLV-III antibody positive individuals, low TH/TS ratio was mainly due to decreased number of TH cells. Most HTLV-III antibody positive cases had low responses to a specific antigen, PPD, while responses to the mitogens PHA and PWM were only slightly affected. In HTLV-III antibody negative cases, 13% had a low TH/TS ratio, mostly due to elevation of TS cells. In this group, mitogen and antigen responses were normal or only slightly affected. The results reinforce the causal relationship between HTLV-III and AIDS and suggest that the cells primarily affected by the virus infection are TH cells, responsible for antigen specific responses. Longitudinal studies are required to find out, what is the relationship of immune response to the development of clinical AIDS in HTLV-III infected individuals.

Acquired Immunodeficiency Syndrome↗

Immunosuppression in homosexual men seronegative for HTLV-III.

Clinical, microbiological, and lifestyle patterns in homosexual men showing in vitro immunological abnormalities were studied and related to the susceptibility to human T-lymphotropic virus type III (HTLV-III) infection. In a cohort of male homosexual volunteers in Finland, 90% were HTLV-III antibody negative. Ten % of the HTLV-III negative cases showed decreased T-helper/suppressor cell ratios, mostly due to elevated numbers of T-suppressor cells. In this immunosuppressed group, more signs of diarrhea, intestinal giardiasis, genital warts, and hepatitis B were observed than in the other HTLV-III antibody-negative study subjects. The type of sexual practice was not associated with the in vitro immune abnormalities. During a follow-up of up to 16 months, 4 initially HTLV-III antibody negative cases showed seroconversion. Three of these had inverted T-helper/suppressor cell ratios prior to the seroconversion. It is concluded that persons showing in vitro immunosuppression are more susceptible to HTLV-III infection when being exposed to the virus or else alteration in T-cell subsets signals a pre-antibody-positive or early phase of HTLV-III infection.

Antibodies, Viral↗

The use of radiolabelled monoclonal antibodies to human milk fat globule membrane antigens in antibody-guided tumour imaging, and administration of therapeutic dose of labelled antibody in wide-spread ovarian carcinoma. A preliminary report.

Monoclonal antibodies generated against human milk fat globule membrane antigens were used in antibody-guided tumour imaging and palliative therapy in a case of wide-spread ovarian carcinoma. Antibody III H 2, which previously has been shown to react with 100% of ovarian cystadenocarcinomas showed a strong reactivity with tissue sections obtained from the primary and metastatic tumours of the patient. Immunoglobulins were purified from mouse ascitic fluid containing III H 2 and labelled with 123I or 131I with the iodogen method. 80 MBq (2 mCi) of 123I-labelled antibody was given intraperitoneally in 500 ml of PBS and the uptake of radiolabel was followed daily with emission tomography. Radiolabel was mainly located in the peritoneal cavity; only a very low activity was seen in the thyroid gland and urinary bladder. A therapeutic dose consisting of 600 MBq (15 mCi) of 131I-labelled antibody was followed nine days later and the localization of the antibody was followed.

Antibodies, Monoclonal↗

Immunohistochemical localization of human liver specific protein using rabbit antisera and the avidin-biotin complex technique.

A sensitive enzymatic avidin-biotin complex technique was utilized to locate the antigenic sites in human liver which react with rabbit antibodies to human liver specific protein (LSP). Depending on the rabbit antiserum used, anti-LSP reactive material was seen in different locations. (1) diffusely distributed in liver parenchymal cells, (2) in both hepatocyte cytoplasm and plasma membrane and (3) in hepatocyte plasma membrane only. The cytoplasmic staining was partially or totally abolished by preabsorption with human kidney homogenate whilst the plasma membrane staining remained uninfluenced. The latter was apparently confined to bile canalicular walls and may be liver specific in contrast to the cytoplasmic reaction which seems to be due to antigen determinants cross-reacting with tissue components in kidney.

Animals↗

Generation of monoclonal antibodies to human milk-fat globule membrane antigens, with special reference to a precipitable secretory product of breast and ovarian carcinomas.

Monoclonal antibodies were generated against protein antigens extracted from human milk-fat globule (HMFG) membranes. Of more than 500 hybridoma clones, 16 secreted antibodies reacting with breast and ovarian carcinoma cells, but not with lymphocytes or macrophages. Five clones were further expanded and characterized; four reacted with plasma membranes of all breast and ovarian carcinomas rested, but also with normal breast. One of the monoclonal antibodies, III D 5, reacted mainly against the cytoplasmic components of breast cancer cells, whereas the reaction with normal or mastopathic breast was against the luminal plasma membranes. The antigen recognized by the antibody was secreted in ascites fluid or pleural effusions of patients with widely spread ovarian or breast carcinomas, and could be demonstrated by immunodiffusion. It is suggested that the antigen is composed of several glycoprotein subunits bearing the same repetitive epitope. This might be the physicochemical basis for its precipitability with a monoclonal antibody.

Animals↗

Comparison of binding of [3H]misonidazole and [14C]misonidazole in multicell spheroids.

Uptake of [2-ring-14C]misonidazole and [3H]misonidazole with tritium in the side chain has been compared in 1-mm EMT-6/UW spheroids using liquid scintillation counting and autoradiography. The uptake of both labeled sensitizers as a function of incubation time was virtually identical. Uptake by the spheroids exceeded levels in the medium by 11/2 to 2 hr and was well modeled as a first-order binding process, with rate constants of 0.00324 hr-1 for 3H and 0.00388 hr-1 for 14C. The similar uptake of the two versions of this sensitizer labeled in different positions suggests that the metabolic actions which allow the drug to bind in hypoxic cells do not principally involve metabolites which separate the number 2 carbon of the imidazole ring from the side chain. The pattern of silver grains in autoradiographs was similar for both labeled sensitizers, with most labeled drug bound in an intermediate zone of cells between the necrotic center and the actively proliferating rim of the spheroids. The superior resolution possible with the tritiated compound showed that both nucleus and cytoplasm in viable looking cells were labeled while pycnotic cells were not labeled.

Animals↗

The relationship of parietal cell, gastrin cell, and thyroid autoantibodies to the state of the gastric mucosa in a population sample.

The occurrence of tissue autoantibodies in relationship to fundal and antral gastritis was examined in an Estonian rural population sample, consisting of 227 persons 15 to 69 years of age. The state of the gastric mucosa was verified with multiple biopsy specimens obtained at direct-vision gastroscopy. Isolated fundal gastritis was characterized as the presence of parietal cell (PCA) and/or thyroid antibodies. PCA was seen only in persons with normal antral mucosa. On the other hand, gastrin cell antibodies (GCA) showed no correlation to the extent of antral gastritis, being seen in normal antrum or in superficial or slight atrophic gastritis but not in moderate or severe gastritis. The findings of our present study thus strengthen the view that the occurrence of PCA is mainly limited to isolated fundal gastritis and excludes the occurrence of antral gastritis. On the other hand, an association of GCA and antral gastritis could not be established.

Adolescent↗

Investigation of the prophylactic effect of tinidazole on the postoperative infection rate of patients undergoing vacuum aspiration.

In a double-blind randomized trial the effect of a single oral tinidazole dose of 2 g, given pre-operatively, on the infection rate was assessed in 210 patients undergoing first trimester abortion by vacuum aspiration (VA) and compared to placebo medication. Anaerobic and facultative anaerobic bacteria were the predominant organisms isolated from the cervix. Six patients in the tinidazole group and 11 from the control group developed a postoperative pelvic infection necessitating antibiotic therapy. In 2 patients, one in each group, hospitalization was necessary. This study indicated that identification of the bacteria present in the cervix before VA does not make it possible to predict the likelihood of the postoperative pelvic infection. Tinidazole administration preoperatively seems to reduce the postoperative pelvic infection rate after VA.

Abortion, Induced↗