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Biomedical subjects

U Berger

Publications and source records attributed to U Berger.

At least 109 records · Page 6Linked to original sources

Oestrogen receptor content of normal breast cells and breast carcinomas throughout the menstrual cycle.

To examine the presence and distribution of oestrogen receptors in the normal breast during the menstrual cycle cytological samples obtained by fine needle aspiration from 69 premenopausal women with normal breasts were analysed immunocytochemically with a monoclonal antibody to oestrogen receptor; samples from 15 postmenopausal women were also analysed. The receptor content of breast cancers from 83 premenopausal women was also determined in relation to when during the menstrual cycle excision was performed. In the normal premenopausal women oestrogen receptors were detected in the nuclei of epithelial cells in 21 out 68 (31%) assessable samples. All 21 of these samples were obtained from the 35 women who were studied during the first half of their menstrual cycle (days 28 to 14). None of the 33 samples obtained during the second half of the cycle contained oestrogen receptors. Samples were assessable in eight of the postmenopausal women, six giving a positive result for oestrogen receptor. Fifty one of the 83 carcinomas were positive for oestrogen receptor, 24 having been excised during the first half of the cycle and 27 during the second half. Production of oestrogen receptor protein is suppressed at the time of ovulation in the normal breast epithelium of premenopausal women. In contrast, breast carcinoma cells either synthesise this protein continuously throughout the cycle or fail to express it despite fluctuations of serum hormone concentrations.

Adult↗

Mammary gland 1,25-dihydroxyvitamin D3 receptor content during pregnancy and lactation.

The purpose of this study was to establish the time course and magnitude of changes in 1,25-dihydroxy-vitamin D receptor activity in rat mammary gland during pregnancy and lactation and to correlate these changes with casein production and alkaline phosphatase activity. Marked increases in both 1,25-dihydroxyvitamin D3 receptor and alkaline phosphatase activities were seen towards the end of pregnancy but the time course of these changes was not synchronous. Receptor activity was first detectable at 11 days of pregnancy with a marked rise in receptor levels at 3 days post-partum. Changes in alkaline phosphatase activity more closely correlated with casein production and peak activity was observed at the time of parturition. We conclude that 1,25-dihydroxyvitamin D3 receptor content increases during pregnancy and lactation and may be involved in maintaining milk calcium concentration.

Alkaline Phosphatase↗

Detection of tumor cells in bone marrow of patients with prostatic carcinoma by immunocytochemical techniques.

We used a mixture of antisera to prostatic specific acid phosphatase, prostatic specific antigen, epithelial membrane antigen and cytokeratin to examine multiple marrow aspirates from patients with local (15) and metastatic prostatic carcinoma (15), and benign prostatic hypertrophy (10). We found moderate to large numbers of tumor cells in the bone marrow of 11 of 15 (73 per cent) patients with known metastatic disease and small numbers of abnormal cells in 2 of 15 (13 per cent) patients with apparently local disease. No tumor cells were found in patients with benign prostatic hypertrophy, and only 2 patients with metastatic disease had tumor cells in the bone marrow when conventional hematomorphological preparations were examined. These findings suggest that immunocytochemistry can increase the detection rate of metastatic prostatic carcinoma cells. Further followup of larger numbers of patients with local carcinoma will reveal whether the presence of micrometastases denotes a poor prognosis.

Acid Phosphatase↗

Epidemiology of meningococcal infections in the Federal Republic of Germany, 1966-1984.

In the Federal Republic of Germany, the morbidity curve of meningococcal infections from 1966-1984 exhibited two maxima in 1970 and 1979 representing morbidity values of 2.9 and 2.3 per 100,000 of the population, and a small peak in 1974. The average morbidity of the 19 years was 2.1/10(5), the lowest morbidity 1.3/10(5) (1983/84). Meningitis occurred on an epidemic scale in 1970 in Bremen, in 1971 in Schleswig-Holstein and 1971-1977 in the Saarland. Most cases were notified during the first four four-week periods of the year, but in two years (1967, 1969), the late-summer peak exceeded the peak of winter/spring. 17.3% of the cases occurred in infants, 51.7% in the first five years of life. Morbidity was highest during the second quarter of the first year. The sex ratio (m:f) of the infections was 1.6:1, but in the aged, morbidity was about the same in both sexes (0.9:1). The case-fatality ratio varied between 7.1% (1977) and 12.1% (1971, 1982) and averaged at 9.7%. It was highest in the aged (37.1%) and second-highest in infants (18.7%). Differences of lethality due to sex could not be demonstrated. Of 1.685 meningococcal strains isolated from CSF and/or blood, 7.3% were of serogroup A, 74.4% of group B, 15% of group C, 1.5% of group Y and 1.1% of group W135. The proportion of group B infections was highest in infants, of group A infections in children (5-10 years), of group C infections in older children and adolescents (10-20 years). The sensitivity of N. meningitidis to sulfadiazine varied with serogroup and year of isolation. Since 1977, practically all group A strains, but only 13% of group B and 9% of group C strains proved to be resistant. Practically all strains were fully sensitive to rifampicin and minocycline; results of trials with spiramycin were not in support of the use of this compound as a chemoprophylactic agent.

Age Factors↗

The relationship between micrometastases in the bone marrow, histopathologic features of the primary tumor in breast cancer and prognosis.

The pathologic features of the primary tumors in 285 patients with breast cancer at the time of initial presentation, and with no clinical evidence of distant metastases, have been analyzed. The results have been compared with the detection of tumor cells in the bone marrow by use of an immunocytochemical method using antisera raised against the epithelial membrane antigen (EMA). The authors found EMA-positive cells (i.e., tumor cells) in the bone marrow of 77 (27%) patients and a significant association between the presence of such EMA-positive cells in the bone marrow and tumor size (P = 0.006) and peritumoral vascular invasion (P = less than 0.001). A possible relationship with estrogen receptor negativity (P = 0.06) also was noted.

Adult↗

Immunocytochemical detection of 1,25-dihydroxyvitamin D receptors in normal human tissues.

We developed an immunocytochemical technique to visualize the receptors for 1,25-dihydroxyvitamin D [1,25-(OH)2D receptor] in cryostat sections of normal human tissues, using a rat monoclonal antibody (9A7 gamma) to the chick intestinal receptor, which has been found to react with mammalian 1,25-(OH)2D receptors. Localization of the antigen was predominantly nuclear, with little cytoplasmic immunoreactivity. Specific staining was seen in the nuclei of many normal epithelial tissues, including liver, kidney, thyroid, adrenal, gastrointestinal tract, breast, and skin. No nuclear staining was seen when tissue sections were incubated with normal rat immunoglobulin G or when the monoclonal antibody was preincubated with a receptor-enriched chick intestinal cytosol preparation. Our results demonstrate that the receptor for 1,25-(OH)2D is localized in the nucleus and widely distributed in normal human tissues.

Animals↗

Immunocytochemical detection of 1,25-dihydroxyvitamin D3 receptor in breast cancer.

We have developed an immunocytochemical technique to visualize the receptor for 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] in cryostat sections of human breast tumors and normal human breast tissue utilizing a monoclonal antibody (9A7 gamma) to chick intestinal receptor which recognizes mammalian 1,25(OH)2D3 receptor. Specific staining was observed in the nuclei of tumor cells. Previous studies by our group have shown that a high proportion of breast tumors bind radiolabeled 1,25(OH)2D3 and we have confirmed this, demonstrating immunocytochemical 1,25(OH)2D3 receptor in 43 of 55 (78%) of breast carcinomas. No correlation with the presence of immunostainable estrogen receptor was found in these breast cancer specimens. Sections of normal breast showed immunoreactivity in the nuclei of epithelial cells of the lobules and ducts. Our results demonstrate that the receptor for 1,25(OH)2D3 resides predominantly in the nucleus of breast carcinoma cells. The reason for its prominent expression in breast cancers is not yet known but may be related to growth regulation.

Adult↗

Presurgical determination of estrogen receptor status using immunocytochemically stained fine needle aspirate smears in patients with breast cancer.

We have developed an immunocytochemical staining procedure (ERICA) using a monoclonal antibody to the estrogen receptor (ER) to determine ER status from samples obtained by fine needle aspiration of primary and recurrent breast cancer tissue (cyto-ERICA). ER status was assessable on 214 of 246 smeared aspirates from breast cancer patients. In 143 (66.8%) assessable smears positive nuclear staining was observed but was completely absent in 71 (33.2%) cases. In 107 cases we were able to compare results with those obtained with the quantifiable dextrancoated charcoal (DCC) radioligand binding technique using surgically excised material. We observed qualitative agreement in 53 of 62 (85.5%) of primary specimens and 16 of 16 (100%) recurrent samples compared to the subsequent DCC result on the same sample. Aspirates obtained from new secondary deposits were also assessed and in 16 of 19 (84.2%) cases results agreed with that established previously by DCC on the primary breast tumor. In a further 6 of 10 (60%) cases the cyto-ERICA result obtained from recurrent samples qualitatively agreed with that determined by DCC on a previous recurrent lesion. A comparison of staining of aspirates was also made against frozen tissue sections stained with the monoclonal antibody (tissue-ERICA). Where comparison was made of primary tumor specimens agreement was observed in 40 of 45 (88.9%) of cases while specimens from secondary lesions agreed qualitatively in 14 of 17 (82.3%) of cases. In a small number of samples where tissue-ERICA was performed on an earlier lesion to that aspirated for cyto-ERICA an agreement of 4 of 5 (80%) was observed. This technique shows good sensitivity in demonstrating ER in aspirate specimens, should therefore permit us to determine ER status before surgery for primary breast cancer, and may also mean that surgery for recurrent disease to determine receptor status is no longer necessary.

Antibodies, Monoclonal↗

Micrometastases in bone marrow in patients with primary breast cancer: evaluation as an early predictor of bone metastases.

The bone marrow of 307 patients with primary breast cancer was examined for tumour cells by immunocytochemistry using an antiserum to epithelial membrane antigen. Micrometastases were found in 81 cases (26.4%) and their presence was related to various poor prognostic factors: spread to lymph nodes, vascular invasion, T stage, and pathological size. The median duration of follow up was 28 months. Seventy five patients relapsed, 60 at distant sites. Of these 60 patients, 26 had micrometastases detected at presentation and 34 were free of micrometastases initially. The relapse free interval was significantly shorter for patients with micrometastases, and these patients had a shorter survival. Analysis of the sites of relapse showed that the test predicted bone metastases only. Thus 10 out of 19 patients (53%) who developed bone metastases at first relapse had micrometastases at presentation compared with only 41 out of 288 patients (14%) who remained free of bone metastases or relapsed in non-skeletal sites. The presence of micrometastases detected at the time of initial surgery in a patient with primary breast cancer is a useful predictor of early relapse in bone and may help in selecting patients for subsequent systemic treatment.

Adult↗

Prediction of endocrine response in breast cancer by immunocytochemical detection of oestrogen receptor in fine-needle aspirates.

An immunocytochemical technique has been developed to detect the oestrogen receptor (ER) in samples obtained by fine-needle aspiration of primary or secondary breast carcinoma tissue. 45 (75%) of 60 samples contained sufficient cells for analysis. 19 (90%) of 21 patients who responded to endocrine therapy had samples with ER-positive cells compared with only 7 (39%) of 18 of those who did not respond (p less than 0.001). This test, which causes little pain to the patient and does not need a surgical biopsy, is as accurate as any other method of predicting the response to endocrine treatment in breast cancer.

Adult↗

Correlation of immunocytochemically demonstrated estrogen receptor distribution and histopathologic features in primary breast cancer.

Frozen sections of breast cancer specimens from 114 patients were assayed for the presence of estrogen receptor (ER) with an immunocytochemical method (ERICA). Significant positive correlations were found between receptor status and various pathologic features, including better histologic degrees of differentiation (P less than 0.001), smaller tumor cell size (P = 0.001), and lower levels of either tumor necrosis (P less than 0.001) or lymphocytic infiltration (P less than 0.001). There was a significant relationship between tubular formation and ER positivity (P = 0.003). This study confirms the results from some previous studies in which ER, assessed by biochemical means, has shown a correlation with good-prognosis pathologic features.

Adult↗

Detection of estrogen receptor in bone marrow from patients with metastatic breast cancer.

We devised a method of detecting estrogen receptors (ER) in bone marrow metastases from patients with breast cancer. The method involves a sequential double-staining immunocytochemical technique, with a monoclonal antibody to ER and a polyclonal antibody recognizing epithelial membrane antigen to confirm the epithelial nature of suspected tumor cells. Twenty-seven patients were assessed: ten were found to have ER-positive tumor cells in the bone marrow; ten had ER-negative cells; and the remaining seven patients had no tumor cells in the bone marrow smears. Of the ten patients with ER-positive cells, eight (80%) either had a response to endocrine therapy, implying that they possess ER-positive breast cancers, or had ER-positive primary tumors as determined by the dextran-coated charcoal biochemical assay (DCC). Of the ten patients with ER-negative cells in the bone marrow, eight failed to respond to endocrine therapy. This technique therefore provides a means of predicting which patients will respond to endocrine therapy, and is particularly important in those patients whose ER status is unknown.

Adult↗

The significance of mu- and delta-receptors in rat pancreatic islets for the opioid-mediated insulin release.

The binding and the insulinotropic effects of enkephalin analogs and of morphine were investigated in rat pancreatic islets. Binding of [3H]Met-enkephalin was saturable, specific and reversible; the rank order for inhibition competition of [3H]Met-enkephalin binding by various compounds was Met-enkephalin = D-Ala2-MePhe4, Met(0)ol enkephalin) greater than Leu-enkephalin greater than morphine with half-maximal inhibitory constants (IC50) of approx. 0.3, 0.3, 100 and greater than 100 nM, respectively. Both the natural enkephalins exerted their insulinotropic effect only at stimulatory glucose concentrations. They had a dual action; whereas insulin secretion was increased at low enkephalin concentration, this effect was reversed at higher concentrations. However, the various enkephalins exerted this effect at different concentrations; only the EC50 values (half-maximal effective concentrations) of their insulinotropic effect were in the same range as the IC50 values of inhibition of [3H]met-enkephalin binding. Cysteamine pretreatment of rats (depletion of somatostatin containing D-cells and decrease in somatostatin secretion) did not change the Met-enkephalin effect on insulin secretion. In contrast to Met-enkephalin, binding of [3H]morphine to islets was not saturable, and morphine had no effect on insulin secretion unless at unphysiologically high concentrations. The data, therefore, indicate that: mu-receptors (affinity for morphine) do not play a role in rat pancreatic islets; delta-receptors (binding site for Met-enkephalin when mu-receptors are not present) mediate the insulinotropic effect of low Met-enkephalin concentrations; and the insulinotropic action of Met-enkephalin is not mediated indirectly via the paracrine effect of an inhibition of somatostatin secretion.

Animals↗

The uptake of lithium ions by synthetic carbonated hydroxyapatite.

Carbonated hydroxyapatites in the presence of F- and Li+ were synthesized. Limited uptake (0.2-1.6 ppm) of Li+ by the apatites was observed, which was proportional to the initially added Li+ and the carbonate concentration of the samples. Fluoride has retarding effect on the Li+ uptake. Li+ causes a decrease in the solubility of carbonated hydroxyapatite.

Animals↗

Nitrite reduction related to serogroups in Neisseria meningitidis.

Among meningococci, nitrite reducing and non-reducing strains occur. From 1319 strains isolated between 1978 and 1984, all serogroup A, D and X isolates reduced nitrite. In strains belonging to the remaining serogroups, nitrite reduction was a variable characteristic. In group B strains isolated in 1978 and 1979 and possibly in group Z' (29 E) strains, sulfadiazine resistance seemed to be coupled to nitrite reduction. Differing from gonococci, N. meningitidis grew well under anaerobic conditions; its growth in the absence of atmospheric oxygen was not stimulated in the presence of nitrite.

Anaerobiosis↗

Differentiation of Gemella haemolysans (Thjøtta and Bøe 1938) Berger 1960, from Streptococcus morbillorum (Prevot 1933) Holdeman and Moore 1974.

Recently, G. haemolysans and S. morbillorum were postulated to be identical organisms, so that consequently their names were synonyms. In the present paper it was demonstrated, that, in spite of many similarities, both species can be differentiated by nitrite reduction, lacking in S. morbillorum, and some further enzymatic activities as well as by antigenic specificity and certain dissimilarities in morphology, growth conditions and their ability to induce beta-hemolysis. S. morbillorum apparently represents a group of strains with divergent properties and might be assigned to the genus Gemella rather than to Streptococcus.

Antigens, Bacterial↗