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Biomedical subjects

H Koren

Publications and source records attributed to H Koren.

At least 19 recordsLinked to original sources
PubMed1992

UV exposure reduces immunization rates and promotes tolerance to epicutaneous antigens in humans: relationship to dose, CD1a-DR+ epidermal macrophage induction, and Langerhans cell depletion.

Increasing UVB radiation at the earth's surface might have adverse effects on in vivo immunologic responses in humans. We prospectively randomized subjects to test whether epicutaneous immunization is altered by prior administration of biologically equalized doses of UV radiation. Multiple doses of antigens on upper inner arm skin (UV protected) were used to elicit contact sensitivity responses, which were quantitated by measuring increases in skin thickness. If a dose of UVB sufficient to induce redness (erythemagenic) was administered to the immunization site prior to sensitization with dinitrochlorobenzene (DNCB), we noted a marked reduction in the degree of sensitization (P less than 0.0006) that was highly dose responsive (r = 0.98). Even suberythemagenic UV (less than a visible sunburn) resulted in a decreased frequency of strongly positive responses (32%) as compared to controls (73%) (P = 0.019). The rate of immunologic tolerance to DNCB (active suppression of a subsequent repeat immunization) in the groups that were initially sensitized on skin receiving erythemagenic doses of UV was 31% (P = 0.0003). In addition, a localized moderate sunburn appeared to modulate immunization with diphenylcyclopropenone through a distant, unirradiated site (41% weak responses) as compared to the control group (9%) (P = 0.05). Monitoring antigen presenting cell content in the epidermis revealed that erythemagenic regimens induced CD1a-DR+ macrophages and depleted Langerhans cells. In conclusion, relevant and even subclinical levels of UV exposure have significant down modulatory effects on the ability of humans to generate a T-cell-mediated response to antigens introduced through irradiated skin.

Antigens, CD↗
PubMed1990

Tissue factor and factor VII messenger RNAs in human alveolar macrophages: effects of breathing ozone.

This study was performed to determine if genes for tissue factor and factor VII proteins are expressed and regulated in vivo in lung macrophages during inflammation. Human alveolar macrophages and alveolar fluids were obtained 18 hours after healthy male adults were exposed, for 2 hours during intermittent exercise, to either air or air with 0.4 ppm ozone, added as a model toxic respiratory agent. Messenger RNA (mRNA) for both tissue factor and factor VII were demonstrated in macrophages isolated after subjects were exposed to unpolluted control air. With the same subjects examined after breathing ozone, the following changes were observed: tissue factor mRNA concentration in macrophages increased 2.6 +/- 0.47-fold. Factor VII mRNA concentration was reduced 0.64 +/- 0.24-fold. Total numbers of macrophages recovered did not change significantly. Ratios of nuclear:cytoplasmic areas of cytocentrifuged macrophages were augmented by 24.8% +/- 3%, giving morphometric evidence that immature cell forms increased in the population. In the lavage, tissue factor activity was increased 2.1 +/- 0.3-fold, while amounts of lipid phosphorous, which estimate total membrane lipids, and estimated volumes of alveolar fluid were not significantly changed. Factor VII activity and fibrinopeptide A levels in lavage were increased approximately twofold. These results using rapidly isolated, noncultured cells indicate that tissue factor and factor VII mRNA are synthesized in the alveolar macrophage population in vivo. In addition, evidence was found that as a result of breathing ozone, a shift in alveolar macrophage maturity occurred in association with tissue factor mRNA, tissue factor activity, and factor VII activity increases, and with formation of fibrinopeptide A in alveolar fluids.

Adult↗
PubMed1990

Phase I studies of recombinant interferon-gamma.

A phase I study of the effects of intravenous administration of interferon-gamma on 31 patients was performed. The effects of dose, schedule, and chronic administration were studied. In the first phase of the study, a dose range of 0.01-500 MU/m2 (0.0002-25 mg/m2) was tested and we found the maximum tolerated dose to be 400 MU/m2; the dose-limiting toxicity with this preparation was hypotension. In the second phase, three different schedules of administration were tested. There were no significant differences in toxicity between a 20 min, a 4 h, or a 24 h infusion of 60 MU/m2 (3 mg/m2). In the third phase, patients received chronic administration of either 1 or 30 MU/m2. Patients given 30 MU/m2 twice a week for 4 weeks showed more symptoms--fever, nausea, and orthostasis--than those treated with 1 MU/m2. No significant changes were seen in natural killer cell activity, antibody-dependent complement cytotoxicity, or monocyte cytotoxicity at any dose. Maximal stimulation of 2',5'-oligodenylate synthetase occurred at low doses (12 MU/m2). Depressed bone marrow colony formation for CFU-GM, BFU-E, and CFU-GEMM in vivo was noted. No objective antitumor responses were noted. This preparation of recombinant interferon-gamma can be given in doses as high as 400 MU/m2. Chronic administration would appear to be limited to 30 MU/m2. However, lower doses may give maximal biologic responses. These studies provide further information on the biologic effects of a wide dose range and a variety of schedules of recombinant interferon-gamma.

2',5'-Oligoadenylate Synthetase↗
PubMed1989

A method for comparison of animal and human alveolar dose and toxic effect of inhaled ozone.

Present models for predicting the pulmonary toxicity of O3 in humans from the toxic effects observed in animals rely on dosimetric measurements of O3 mass balance and species comparisons of mechanisms that protect tissue against O3. The goal of the study described was to identify a method to directly compare O3 dose and effect in animals and humans using bronchoalveolar lavage fluid markers. The feasibility of estimating O3 dose to alveoli of animals and humans was demonstrated through assay of reaction products of 18O-labeled O3 in lung surfactant and macrophage pellets of rabbits. The feasibility of using lung lavage fluid protein measurements to quantify the O3 toxic response in humans was demonstrated by the finding of significantly increased lung lavage protein in 10 subjects exposed to 0.4 ppm O3 for 2 h with intermittent periods of heavy exercise. The validity of using the lavage protein marker to quantify the response in animals has already been established. The positive results obtained in both the 18O3 and the lavage protein studies reported here suggest that it should be possible to obtain a direct comparison of both alveolar dose and toxic effect of O3 to alveoli of animals or humans.

Administration, Inhalation↗
PubMed1985

On the therapy of induratio penis plastica (Peyronies disease) by means of radium moulages.

In the past 50 years 2210 patients suffering from induratio penis plastica were admitted to our department. In 69% of the cases an improvement could be observed within 18 months after radium moulage therapy. By improving radium protection the therapy may now be performed without any significant exposure of the testes. A 15 year old patient is the youngest case reported in world literature. Trend analyses show a case shift towards the senium.

Adolescent↗
PubMed1984

Severe combined immunodeficiency with natural killer-cell predominance: abrogation of graft-versus-host disease and immunologic reconstitution with HLA-identical bone marrow cells.

A 3 1/2-month-old infant with severe combined immunodeficiency was found to have an unusual blood lymphocyte phenotype. Thirty percent of her cells formed rosettes with sheep erythrocytes, but only 7.9% reacted with the pan T monoclonal antibody OKT3, and 5% reacted with an antibody (OKT4)-recognizing T-helper cells. Surprisingly 19.4% of her cells reacted with an antibody (OKT8)-recognizing T-suppressor cells and 94% reacted with OKT10 . Few reacted with other monoclonal antibodies detecting cellular activation antigens. Despite absence of T or B cell function, her monocyte-depleted blood lymphocytes caused a high degree of specific lysis of 51Cr-labeled K562 erythromyeloid cells in a natural killer-cell assay. Most of her lymphocytes were large and had azurophilic granules and a monocytoid nucleus. Because she had received a nonirradiated, unrelated red-cell transfusion 3 days earlier, 4.8 X 10(9) nucleated bone-marrow cells from her HLA-identical brother were given shortly after admission. Two days later a graft-versus-host reaction began but subsided completely within 3 days. On day 15 posttransplantation, a profuse secretory diarrhea began, accompanied by a rise in her serum IgE from 4 to 3000 IU. With engraftment, the number of T10+ cells and natural killer-cell function fell to normal, and full immunologic reconstitution was achieved.

Antibodies, Monoclonal↗
PubMed1983

Phase I study of pharmacological and immunological effects of human lymphoblastoid interferon given to patients with cancer.

An extensive Phase I evaluation of human lymphoblastoid interferon has been completed which, in addition to describing its clinical and pharmacological effects, emphasized a broad-scale evaluation of the immune response as a function of interferon dosage. Dose-limiting toxicity was generally due to constitutional symptoms which are remarkably similar to those produced by influenza, although transient peripheral and central neurotoxicity (including deterioration in cognitive and behavioral functions) is observed at higher doses. It is difficult to establish "clean" dose-response effects except for fever and bone marrow suppression, neither of which is a major dose limitation. Enhancement of the immune system was limited to natural killer cells which had a complex dose-response relationship, whereby low interferon concentrations were less stimulatory (than were high doses) following a single dose but gave more sustained stimulation over a 5-week course of 3 times per week i.m. administration. The effects on various measures of monocyte function and of nonspecific immunity (hypersensitivity, immunoglobulins, complement) were negative. We suspect that in practice it may be difficult to exploit the narrow dosage window of immunostimulation, but it is important to note that the nontoxic lower doses were more stimulatory than were the very high doses which are being used in numerous clinical trials.

Adult↗
PubMed1982

Mononuclear-cell infiltration in ovarian cancer. II. Immune function of tumour and ascites-derived inflammatory cells.

Mononuclear cell fractions were isolated from blood, ascites and solid tumours of patients undergoing surgery for Stages III and IV adenocarcinoma of the ovary, and evaluated for their response in NK, ADCC and PHA assays. Control experiments with the same fraction of normal blood indicated that these responses were not influenced by the enzymes used to isolate the tumour and ascites inflammatory cells. The inflammatory cell fractions isolated from both tumour sites which sedimented in the velocity range of blood mononuclear cells were adequate in number and composition for comparison with similar cells from blood. E RFC values in both ascites and tumour fractions exceeded those of patient blood. However, there was a marked difference in distribution of the T subsets between blood, ascites and tumour, which could cause the variable test results between the different cell sources. PHA responses of patient blood and ascites fractions were about half that of normal blood. Tumour-infiltrating lymphocytes (TIL) were less than 10% as responsive as normal blood. The depressed PHA responses of the TIL were not due to the presence of a suppressor cell population. NK activity of patient blood was less than that of normal blood, but not as much as the ascites of TIL cells. The activity of the ascites-derived lymphocytes was enhanced by treatment with interferon. ADCC activity against both CRBC and SB cells was normal or higher than controls in patient blood, and depressed in the ascites-derived fractions. TIL responded to less than 10% of the patient blood values. The results indicate a lack of response by ascitic and TIL cells in assays dependent on FcR-bearing effector cells and a greater loss of PHA-reactive cells from the tumour than from blood and ascites. These data could result from intratumour inactivation, or a failure of the particular subset to localize either in the ascites or the tumour site.

Adenocarcinoma↗
PubMed1982

Mononuclear-cell infiltration in ovarian cancer. III. Suppressor-cell and ADCC activity of macrophages from ascitic and solid ovarian tumours.

Macrophages have been isolated from ascitic and collagenase-dispersed tumours from patients undergoing surgery for ovarian cancer. Macrophages were present in varying proportions in both sites, though the ration of macrophages to tumour cells was higher in ascites. Marked variation in size (as detected by sedimentation velocity) and cytochemical markers in the macrophages was noted. Highly enriched macrophage fractions were isolated from the ascites and collagenase-dispersed solid tumours by a combination of sedimentation velocity and selective EA RFC or adherence techniques. Suppressor activity in the PHA assay was detected in tumour macrophages (4/10 giving less than 50% inhibition), ascitic macrophages (1/15) and blood monocytes (2/7). Lymphocyte fractions from tumours were unresponsive to PHA and failed to suppress the blood response. Suppressor activity was also present in the purified tumour-cell fraction of 6/14 patients. ADCC activity was tested in a few patients. When the activity was determined against the SB target cells, tumour-derived macrophages were inactive, whereas the ascitic fraction showed low but significant activity which averaged much lower than patients blood values. The ADCC assays carried out with the CRC target cell indicated activity within the range of patient blood values in 4/4 ascites and 2/4 tumour macrophage fractions. Cytotoxicity was also assessed against co-purified autologous tumour cells. Although activity was detected in many of the tests, the results seemed to reflect target cell sensitivity. There appeared to be a correlation between cytotoxicity with test macrophages and normal blood mononuclear cells. The results indicate that the cytochemical heterogeneity and the variation in size between macrophage fractions is associated with a spectrum of activities.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1978

[Investigations of the influence of radiation therapy upon the course of the DNA repair in peripheric lymphocytes and tumorous tissues from patients with malignant disease (author's transl)].

The influence of radiation therapy upon the capacity of DNA repair in peripheric lymphocytes and tumorous tissues was studied in eleven patients with malignant manifestations. A comparison was made between the effects of short-term and of long-term irradiation. The individual cases presented differing results. An enhancement of DNA repair as well as a diminution was observed in peripheric lymphocytes as a response to irradiation. In tumorous tissues, on the contrary, a total inhibition of DNA repair was generally found.

Aged↗
PubMed1976

[On the radiotherapy of the carcinoma of the tonsils (author's transl)].

In the period 1932 to 1975 469 patients were admitted with a malignoma of the tonsils. 74,9% were stage T3. Nearly 50% showed up with involvement of fixated and suspicious lymphnodes. The relation men to women was 80:20. The highest incidence was found in the age group 61-70 a. The patients were treated using Radium: interstitial implants and external radiation, later Cobalt sources and the Betatron. The over-all 5 year survival rate is 21.6% for carcinomas and 32% for sarcomas. In the case histories there are predominantly late ones because difficulties in swallowing are neglected for a long time. The prognosis for cases stage T3 is rather bad. Considering the literature our material is the greatest out of a single department.

Aged↗
PubMed1975

[Therapy of penile plastic duration using radium moulages].

During the last 42 years, 1524 patients with I.p.p. were treated in our department. In 69% of the cases (173 out of 248) an improvement was observed within 13 months, following therapy with radium moulages. Through improved radiation protection this therapy can be performed without undue exposure of the testes. A 15 year old patient ist the youngest case on record. Trend-calculations show a progressive tendency of this disease in later years.

Adult↗