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Biomedical subjects

E Heise

Publications and source records attributed to E Heise.

At least 19 recordsLinked to original sources
PubMed2001

HLA phenotypes of ESRD patients are risk factors in the panel-reactive antibody (PRA) response.

To determine whether recipient HLA phenotypes are correlated with an increased or decreased risk of alloantibody sensitization in end-stage renal disease (ESRD) candidates for first or repeat kidney transplantation; we analyzed 19440 kidney allograft recipients consisting of 13,216 Caucasians and 6224 non-Caucasians transplanted between 10/87 and 11/98 at South-Eastern Organ Procurement Foundation (SEOPF) member institutions. Relative risk values and 95% confidence limits were obtained using Wolfe's method. Logistic regression was used to adjust for covariates that influence sensitization, i.e. ethnicity, gender, age, pregnancies, transfusions, primary/repeat transplant and living versus cadaver donor. Univariate analysis of the entire cohort indicated that nine HLA allelotypes (DR1,4,7; B8,12,40; A1,2,11) were associated with a significantly reduced risk of sensitization, and five allelotypes (B42,B53; A 10,19,36) were associated with an increased risk of PRA responses. Corrected for the number of statistical comparisons, recipients with DR1, DR4, A1 or A2 were 15% less likely to be sensitized per allelotype. Recipients with B42, B53 or A36 were at increased risk of preformed antibodies, after correction of the P value, for an average of 38% increased risk per allelotype. In the multivariate analysis, HLA phenotypes identified as independent risk factors associated with protection against sensitization were DR1,4,7; B12(44,45); and A1,2, with an average reduced risk of 9% per allelotype. The only independent susceptibility allelotype was A36 with an increased risk of 29%. The A10 (25,26,34,66) group reached borderline significance. We also looked for HLA-DR,-B,-A combinations that could potentially represent protective or at risk haplotypes/genotypes. Stepwise logistic regression identified five combinations associated with protection: DR1-B35-A3; DR1-B35-A2; DR1-B44-A2; DR4-B44-A2; DR7-B57-A1 (RR range 0.83-0.63) with 27% average reduced risk per combination. Phenotype combinations associated with an increased risk of sensitization were: DR2-B44-A2; DR2B53-A2; DR3-B8-A1: DR3-B42-A30; DR6-B42-A30; DR11-B53-A30 (RR range 2.76-1.48) with an average increased risk of 70% per combination. This study provides strong evidence that HLA-linked genes influence the anti-HLA PRA response. The magnitude of the altered PRA response risk in DR-B-A combinations was approximately twice that of the allelotypes at individual loci. HLA-DR genes seemed to contribute most of the altered risk. The correlations between DR types and PRA responsiveness are consistent with the DR types previously regarded as predictors of kidney graft survival. The magnitude of increased PRA risk attributable to an allelotype or combination was approximately twice that associated with a decreased risk. We conclude that some HLA class II-linked genes modulate the PRA response in a clinically significant manner. This immune response gene (Ir) regulation probably operates through polymorphic HLA molecules in their physiologic roles of antigen processing and presentation to helper T cells.

Adult↗
PubMed1993

Estradiol receptor and prognosis in human breast cancer and its metastases.

Follow-up of 86 patients for at least 40 months confirmed age dependency of receptor binding capacity in primary breast tumors but not in lymph node metastases. In most cases receptor binding capacity was higher in lymph node metastases than in primary tumors. Prognosis of the disease expressed as percentage of patients who survived and had a disease-free interval is related to receptor binding capacity of the primary tumors investigated. In our investigation, a value of 60 fmol/mg protein seems to be a suitable cut-off value to distinguish between breast cancer patients with good and bad prognosis. Receptor levels of lymph node metastases showed a similar behaviour as those of primary tumors related to percentage of patients who survived, but not to disease-free interval.

Adult↗
PubMed1988

Activation of the estrogen receptor from N-nitrosomethylurea-induced rat mammary tumors.

The activation of the estrogen receptor (ER) from N-nitrosomethylurea (NMU)-induced rat mammary tumors was studied in vitro. The activation of the receptor induced by heating of the cytosol containing occupied ER was measured by a 3-4-fold increase of receptor binding to nuclei in comparison with the nuclear binding of the nonactivated ER. The activation of the ER was further shown by alteration of the elution profile from DEAE-cellulose. A shift of the receptor peak from 234 mM (Peak II, nonactivated ER) to 70 mM (Peak I, activated ER) phosphate buffer could be obtained. The overall recoveries of activated ER following chromatography on DEAE-cellulose were significantly lower than the recoveries of the nonactivated ER, 71 and 85%, respectively. Binding of the activated ER to nuclei and chromatography of the supernatant which is not able to bind to nuclei on DEAE-cellulose resulted in a decrease of Peak I and in an increase of the overall recovery. These findings suggest that the nuclear bound ER consists of two parts. One is represented partially by Peak I of the elution profile and the other one by that part of the receptor which can not be eluted from the column under the conditions used. Furthermore, the dissociation of tritiated estradiol (E3H) from the nonactivated ER followed a two component exponential function whereas after activation a monophasic dissociation curve could be observed. The mean half times for the dissociation of E3H from the activated and nonactivated ER were 101 and 7.2 min, respectively. Finally, the nonactivated molybdate stabilized ER sedimented in 5-20% sucrose density gradients as two peaks, one at 9.5 S and the other at 4 S. After activation of the ER only the smaller 4 S peak was evident. Molybdate inhibited the activation of the ER measured by nuclear binding assays, sucrose density gradient analysis, dissociation kinetics or ion exchange chromatography but not completely in every case.

Animals↗
PubMed1986

Binding of estrogen receptor from N-nitrosomethylurea-induced rat mammary tumors to nuclei.

The binding of the cytoplasmic estrogen receptor (ERc) from N-nitrosomethylurea (NMU)-induced rat mammary tumors to the nucleus using a cell-free system is described. All tumors studied were estrogen-receptor-positive and most of them were hormone-dependent. Sixty-two percent of all tumors investigated (n = 134) decreased in size more than 30% 4-5 days after ovariectomy. Brief heating of the cytosol loaded with tritiated estradiol induced activation of the ERc measured by an increase of nuclear binding activity. Temperature-dependent activation was evident in every case. The optimal time and temperature of activation were 15-60 min at 30 degrees C. After denaturation of the ERc by heating for 20 min at 56 degrees C only small parts of free estradiol could be bound to nuclei. Mg2+ ions and EDTA inhibited the nuclear binding of the receptor. The nuclear binding assay was performed for 1 hr at 0-4 degrees C. After this time the activated ERc was bound nearly maximally to nuclei. Under optimized conditions 50-60% of the ERc could be bound to nuclei maximally. Using the same medium for the preparation of crude and purified nuclei the binding of the receptor to both kinds of nuclei was similar. Na2MoO4 prevented the activation of the ERc from NMU-tumors completely but did not influence the binding of the previously activated receptor to nuclei.

Animals↗
PubMed1985

Spontaneous and aggregated IgG induced rheumatoid factor producing cells in rheumatoid arthritis.

Seropositive rheumatoid arthritis (RA) patients were found to have high numbers of spontaneously occurring cells making rheumatoid factor (RF) reactive with human IgG as measured by a RF plaque forming cell (RF-PFC) assay. There was a significant positive correlation between the number of RF-PFC and both disease activity measured by the sedimentation rate and RF titer measured by the RA latex test. Aggregated IgG and pokeweed mitogen were equally effective stimulators of RF-PFC in cultures of RA peripheral blood mononuclear leukocytes. The rheumatoid ratio of helper (T4): suppressor (T8) T lymphocytes was also significantly increased over the ratio of normal controls, but this ratio did not correlate with the number of RF-PFC. Aggregated IgG or immune complexes may be responsible for stimulating RA RF-PFC in vivo.

Adult↗
PubMed1985

Studies on assay of estradiol binding proteins by cytochemical and immunocytochemical techniques in human breast tumors and other tissues.

Estradiol binding proteins in frozen sections of human breast tumors, ovarian carcinomas, hypernephromas, rat uteri and cow udders were demonstrated by fluorescent labeled estradiol bovine serum albumin conjugate (cytochemical or direct method). The specificity of the binding of estradiol conjugate to tissue sections was tried to approach by addition of various steroid or non-steroidal competitors. The estradiol conjugate binding sites were practically not present in sections of human spleen, cross muscle and colon muscle.

Adult↗
PubMed1985

[Correlation of the results of in vitro tests (cell cultures and receptor analyses) of human breast cancers in relation to their hormone dependence].

Pretherapeutic parameters are demanded for the hormonal treatment of metastasing breast cancer. Many methods have proved to be ineffective in the assessment of the hormone sensitivity until now (determination of concentrations of steroid hormones in serum and urine or Barr's sex-chromatin). Investigations carried out hitherto on estradiol receptor content or on hormone sensitivity based on in-vitro cultures were promising. They caused us to compare both methods at the same mamma carcinoma tissue. The results of this study showed that no unequivocal correlation between receptor status and the results of in-vitro cell culture tests for hormone sensitivity could be found. Although all in all the results of both methods are almost identical in percentage, there are however substantial deviations between the results in the directly corresponding comparison of each single tissue sample.

Breast Neoplasms↗
PubMed1983

Studies of random Black and White populations in North Carolina: hla antigen profile.

As HLA testing is becoming a major vehicle for parentage determination with non-excluded, alleged fathers being compared to their racial peers, it is important to ensure that the population data used accurately reflect the genetic profile of the region from which the alleged fathers are drawn. This paper presents data on the HLA profile of Black and White residents of North Carolina. Significant differences were observed for certain antigens when the North Carolina data were compared to nationally derived population tables. Differences were observed for B7 (increase) and Bw16 (decrease) in Whites and A10 (decrease), B7 (increase) and Bw42 (decrease) in Blacks. Internal controls comparing the testing from the two participating centers showed complete agreement for White persons, but a significant difference for B5 between the two Black populations.

Adult↗
PubMed1983

Kinetic data of cytoplasmic estradiol receptor.

Association and dissociation equilibrium constants and rate constants have been determined in human breast cancer tissues, human lymph node metastases, experimentally induced rat mammary tumors and pooled uteri of normal rats. When the dissociation constants gained from the Scatchard plot applying the Chamness correction were compared to those calculated as the quotient of the rate constants, relatively large differences were found, predominantly due to the values of measured association rate constants. In contrast, there were no specific differences between the constants of distinct tissues. The differences among the association rate constants were presumably caused by a contamination of cytosols by steroid binding proteins of serum. Increasing amounts of serum added to tissue samples resulted in an increasing interference with the determination of the dissociation constants using the Scatchard analysis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1982

Genetic predictors of patient response and side effects in the treatment of rheumatoid arthritis with a high dose nonsteroidal antiinflammatory drug regimen.

Clinical, laboratory, genetic, and radiologic studies were evaluated for 18 patients with rheumatoid arthritis who were treated for a mean of 16.6 months with a regimen involving supplementary aspirin and piroxicam, an investigational, nonsteroidal antiinflammatory agent. Although improvement in disease activity was seen, progression was evident on successive radiographs. Disease activity was not associated with the presence of any of the genetic markers. Peptic ulcers developed in 33% of patients, all of whom had type O blood. ABO blood typing may therefore be useful in patients with rheumatoid arthritis before consideration of therapy with potentially ulcerogenic drugs.

Adult↗
PubMed1982

Estradiol receptor in human breast cancers throughout the menstrual cycle.

The existence and the concentration of the estradiol receptor (ER) in breast cancers of pre- and postmenopausal patients were measured. ER status and concentration are significantly higher in cancers of postmenopausal women. Breast cancers operated at various phases of the menstrual cycle showed remarkable differences in ER incidence and concentration. The highest values were found in the early proliferative phase, whereas the ER incidence is lowest in cancers which were operated at early secretory phase. ER concentrations found in late proliferative and late secretory phases are significantly lower than those found in cancers of postmenopausal patients. Statistically significant differences of the ER concentrations between the various phases of the menstrual cycle could not be secured.

Adult↗
PubMed1982

Insulin binding and response to insulin of adipocytes from thyroxine-treated rats.

Insulin binding to isolated fat cells from rats rendered hyperthyroid by daily injections of T4 (1 mg/kg) for 5 days was approximately doubled. The Scatchard curves reflected a large increase in receptor number, as well as an elevation in affinity of the high affinity binding sites. The response to insulin of the fat cells, however, was not increased accordingly: glucose incorporation into lipid in the presence of insulin did not differ significantly from that observed in the control group, whereas the effect of insulin on the lipolytic response to isoprenaline (isoproterenol) was even reduced in the T4-treated animals. T4 treatment had thus dissociated insulin binding from the metabolic effects of insulin, since the increase in membrane receptors was not paralleled by an enhanced effect of the hormone. Since levels of serum insulin were increased in the treated animals, the increase in number of insulin receptors was not mediated by reduced exposure to insulin. Propranolol failed to fully antagonize the effect of T4 on insulin binding, and reserpine treatment even enhanced it. It seems unlikely, therefore, that the increase in insulin receptors of adipocytes results from an augmented response to endogenous catecholamines in T4-treated rats.

Adipose Tissue↗
PubMed1982

[Oestradiol receptors in endometrial carcinomas (author's transl)].

Tissue samples taken from endometrial carcinomas as well as from normal and hyperplastic endometria were tested for oestradiol receptors. Roughly one and the same amount of receptors was recordable from all three tissue groups. In premenopausal women, receptor levels were lowest in the advanced phase of secretion. All tumour patients so far have survived without recurrence. Therefore, no correlation has been established, as yet, between receptor level and prognosis, in a way similar to what has been found in cases of mammary carcinoma.

Adult↗
PubMed1981

Comparison of estradiol receptor investigations and histochemical investigations on enzymes in human mammary cancers.

The best way to predict the responsiveness of human breast carcinomas to hormone therapy is to investigate the estradiol receptor-binding abilities of these tumors. This binding induces many hormone-regulated changes in the activities of several enzymes. Therefore, enzyme activities after short-term organ culture exposed to added hormones were tested to see whether a correlation of enzyme activities exists with estradiol receptor binding. The results from both the estradiol receptor investigations and histochemical investigations on enzymes revealed a high degree of conformity, which confirms the existence of such a correlation. However, for this reason histochemical investigations on enzymes cannot eliminate the discrepancy between the experimentally verified existence of estradiol receptor binding and the response of mammary tumors to hormone therapy, which is not higher than 50-60%.

17-Hydroxysteroid Dehydrogenases↗
PubMed1981

[Steroid hormone receptors and their relevance for the therapy of mammary cancers (author's transl)].

Estradiol receptors which are detectable in the cytoplasma of cells of human breast cancers can be used successfully for evaluating the hormone sensitivity of these tumours. Receptor negative cancers generally do not respond to endocrine therapeutical procedures whereas receptor positive cancers respond in 60% of cases. It is conceivable that this non sufficient correlation is caused by an impairment in the hormone receptor interaction, The simultaneous determination of estradiol and progesterone receptors in the tumour tissues increases the correlation between receptor status and hormone sensitivity to 80 percent. There exists a high degree of conformity between the receptor status of primary tumours and metastatic lymph nodes as well as recurrences.

Adrenal Cortex↗