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PubMed2004

Mammary histidine decarboxylase vulnerability to enzyme antisense oligonucleotides: histamine and polyamine systems cross-talk.

Histamine system is suggested to have a role in mammary gland growth regulation, differentiation and functioning during pregnancy and lactation. Histidine decarboxylase activity undergoes significant changes during pregnancy and lactation. Pregnancy associated elevation of HDC activity and mRNA transcript in mouse mammary gland was successfully affected by enzyme antisense oligonucleotides treatment. The enzyme activity of resting mammae was unaffected as it lacked inducible pool of HDC. The short-term mammary histamine shortage evoked influenced the mRNA expression of histamine receptors (H1 and H2) and ornithine decarboxylase during pregnancy. There were essentially no morphological changes in the mammary gland upon the treatment, however, adipocytes neighbouring alveolar structures were more pronounced. These findings further substantiate the role of histamine in mammary gland physiology and emphasise presence of common motifs of biogenic amines and polyamine metabolism as well as mutual interferences implicating observed "cross-talk" phenomenon.

Animals↗
PubMed1987

Increased fibrinolytic activity after surgery induced by low dose heparin.

Forty women undergoing surgery under general anaesthesia for hyperplasia mammae were randomized to treatment with low dose heparin (5000 IU twice daily) or not. Preoperatively, and repeated on the 3. postoperative day, assays of euglobulin clot lysis time (ELT) after venous stasis, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI) were performed. Compared to the control group heparin was found to give a significant rise in t-PA antigen before (24.0 vs. 11.2 ng/ml, p = 0.02), and especially after venous stasis (104.8 vs. 47.3 ng/ml, P = 0.007). t-PA activity was also significantly more increased after venous stasis in the heparin group than among the controls (4.2 vs. 1.4 U/ml, p = 0.04). This was also reflected in the ELT after venous stasis which was significantly shorter in the heparin group (p = 0.01). No differences in PAI were found between the groups. The present results point to a heparin-induced increase of t-PA synthesis in the endothelium, also giving rise to an increased level of circulating t-PA as measured immunologically. This effect of small dose heparin may play an important role in the prophylaxis against thrombo-emboli, in addition to the anticoagulant effect.

Adult↗
PubMed1990

Fundamental voice frequency in female puberty measured with electroglottography during continuous speech as a secondary sex characteristic. A comparison between voice, pubertal stages, oestrogens and androgens.

The change of fundamental voice frequency in continuous speech in female puberty was analysed in 47 girls by comparison of 2000 consecutive electroglottographic cycles in a reading situation. The results were compared with serum concentrations of androgens (dihydroepiandrosterone, delta-4-androstenedione, testosterone, and sex hormone binding globulin), oestrogens (oestradiol, oestrone, and oestronesulphate), and somatic puberty (weight, height, mamma stages, and pubic hair stages). Fundamental frequency in continuous speech was related only to oestrone r = -0.34, (P less than 0.05). But the tone range in continuous speech and the lowest tone in the phonetogram were found to be significantly correlated with many of the pubertal and hormone parameters. All these correlations could be explained by a common age-dependency. By multiple regression analysis different sets of variables for prediction of speaking fundamental frequency were found before and after menarche.

Adolescent↗
PubMed2004

Effect of in vitro estrogenic pesticides on human oestrogen receptor alpha and beta mRNA levels.

Nine widely distributed pesticides were recently demonstrated to possess potential estrogenic properties in oestrogen receptor (ER) transactivation and/or E-screen assays. We tested the effect of these nine pesticides on the human ERalpha and ERbeta mRNA steady state levels in the mamma cancer fibroblast MCF-7BUS cells using on-line RT-PCR. Like 17beta-oestradiol (E2), fenarimol significantly decreased the ERalpha and increased the ERbeta mRNA level. Endosulfan and pirimicarb alone decreased the ERalpha mRNA level weakly. After co-exposure with E2, all the tested pesticides counteracted the E2-induced decrease of the ERalpha mRNA level, but only significantly for prochloraz, dieldrin, and tolchlofos-methyl. Alone no pesticides affected the ERbeta mRNA level significantly, but chlorpyrifos increased the mRNA level weakly. Co-exposure with E2 elicited a significant increased ERbeta mRNA level by prochloraz, fenarimol, endosulfan, dieldrin, and tolchlofos-methyl, whereas no significant effect of the carbamate pesticides on the ERbeta mRNA level was observed. This study demonstrated that organochlor and organophosphorous pesticides possess the ability to interfere with the ERalpha and ERbeta mRNA steady state levels.

Cell Line, Tumor↗
PubMed2004

The stability of historical control data for common neoplasms in laboratory rats: adrenal gland (medulla), mammary gland, liver, endocrine pancreas, and pituitary gland.

Time-related changes in the incidences of spontaneous neoplasms in adrenals (medulla), mamma, liver, pituitary, and (endocrine) pancreas were assessed statistically in Wistar, Sprague-Dawley, and F344 rats employed by BASF, Germany and major European contract research organizations over the last 20 years. Negative trends (7 of 80 cases) were observed for pituitary pars distalis adenomas in Sprague-Dawley males and females, for pancreas islet cell adenomas in BASF Wistar males and females, for benign adrenal pheochromocytomas in Sprague-Dawley males, for malignant pheochromocytomas in F344 males, and for mammary gland fibroadenomas in BASF Wistar females. Positive trends (13 of 80 cases) were observed for benign pheochromocytomas, mammary gland adenocarcinomas, and pancreas islet cell carcinomas in HanWistar females, for malignant pheochromocytomas and islet cell carcinomas in BASF Wistar males, for benign pheochromocytomas and islet cell adenomas in F344 males, for mammary gland fibroadenomas in Sprague-Dawley females, and for benign hepatocellular tumors in HanWistar males and females, and in BASF Wistar and Sprague-Dawley females. In 60 of 80 cases there were no statistically significant trends. These results indicate that the majority of tumor types showed no time trends and that, in each rat strain, certain tumor types are susceptible to slight positive or negative time trends. Accordingly, the validity and use of historical control data should be based on an organ- and strain-specific statistical analysis of tumor incidence over time.

Adrenal Gland Neoplasms↗
PubMed1993

Immunohistochemical detection of lactoferrin in different human glandular tissues with special reference to the exocrine pancreas.

The immunohistochemical detection of lactoferrin was carried out with the PAP technique on pancreatic tissue samples of 23 patients, operated for acute (13) or chronic (4) pancreatitis as well as for adenocarcinomas (6). In order to control our immunohistochemical technique and the antisera produced by us we studied some tissue samples of human mammary gland and parotis. We detected lactoferrin in the glands of parotis and mammae as well as of their secretions. In the pancreatic tissue we found a positive reaction only in granulocytes of inflammatory areas with the exception of a luminal reaction on the surface of acinar cells in one case of pancreatic adenocarcinoma. We would like to interpret our results with the hypothesis of granulocytic origin of immunochemically detectable lactoferrin in the pancreatic juice of patients, especially in cases of chronic pancreatitis.

Adenocarcinoma↗
PubMed1998

Bilateral, tumorlike diabetic mastopathy-progression and regression of the disease during 5-year follow up.

Diabetic mastopathy is a recently described collection of radiographical and histological features found in dense fibrous masses of the breast in long standing Type I diabetes. We describe the first case of bilateral disease with the alternate progression and regression of the disease over a 5 year period. A 45-year-old woman has been affected of insulin dependent diabetes mellitus (IDDM) for 21 years. She developed palpable mass retromamillar of the right side, indistinguishable radiographically from cancer. The histology showed a diabetic mastopathy (DMP) with B-lymphocytic ductitis and lobulitis, a discrete monocellular vasculitis and a keloid-like fibrosis. After 22 months she developed a suspicious palpable mass contralateral on the left side. The FNAB presented an identical morphology on histology. Additionally 10 months later there were no palpable masses of both mammae. Mammographically no suspect alterations were observed. One year later the clinical and mammographical examination showed similar findings, mentioned before. The pathogenesis is still obscure and includes the hypothesis of extracellular accumulation, secondary to prolonged hyperglycemia in IDDM, production of alternated non-enzymatic glycosylated end products with neoantigen formation, B cell predominant inflammation with autoimmune response against neoantigens and cytokine release secondary to the autoimmune response.

Biopsy↗
PubMed1993

Frequency of spontaneous tumours in NMRI mice in 21-month studies.

Tumours occurring in 900 male and 900 female mice of the strain NMRI (BOR: NMRI (SPF Han), breeder: Winkelmann, Borchen) employed as control groups in 18 different studies lasting for 21 months on average (study No. 8 for 20 months, study No. 5 for 24 months) were compiled on the basis of histopathology reports. 883 male and 874 female mice were evaluated. The remaining animals were unavailable due to autolysis. A total of 1522 tumours (689 in males, 833 in females) were seen in 1061 mice (493 males, 568 females), 830 of which were classified as malignant (318 in males, 512 in females). About 70% of all primary tumours were located in the haemolymophoreticular tissue, lungs, ovaries, adrenals and uterus. Average incidences of primary tumours found in the following organs were: haemolymphoreticular tissue 22.9%, lungs 21.6%, ovaries 12.1%, adrenals 6.9%, uterus 6.6%, liver 4.4%, Harderian gland 4.4%, pituitary 3.5%, mamma 3.3% and various other organs with a tumour frequency below 3%. Male mice exhibited markedly more tumours of the lungs, adrenals, liver and Harderian glands, while tumours of the haemolymphoreticular tissue and pituitary were predominant in females. A comparison of these data with those from preceding two-year or life-span studies using NMRI mice from other breeders revealed a certain increase in primary tumours of the adrenals, Harderian glands as well as pituitary. This result could be due to more frequent examinations.

Animals↗
PubMed1999

Antimicrobial, antitumor and antileishmania screening of medicinal plants from Guinea-Bissau.

Following an ethnobotanical search carried out in Guinea-Bissau, eighteen extracts derived from sixteen medicinal species were screened for antimicrobial, antitumor and antileishmania activity. Significant antitumor activity was found for Holarrhena floribunda against KB (squamous carcinoma), SK-Mel 28 (melanoma), A 549 (lung carcinoma) and MDA-MB 231 (mamma carcinoma) cell lines, with corresponding IC50 values of 7.9, 9.0, 3.4 and 9.9 micrograms/ml. Khaya senegalensis and Anthostema senegalense exhibited a significant activity against Leishmania donovani with IC50 values of 9.8 and 9.1 micrograms/ml, respectively. Most of the extracts showed week or moderate antibacterial and antifungal activity, with MIC values in the range 0.25-1.0 mg/ml. Active extracts were submitted to bioassay-guided fractionation, and the IC50 and MIC of the active fractions were determined.

Animals↗
PubMed1998

Human progesterone receptor A and B isoforms in CHO cells. II. Comparison of binding, transactivation and ED50 values of several synthetic (anti)progestagens in vitro in CHO and MCF-7 cells and in vivo in rabbits and rats.

The human progesterone receptor A and B isoforms (hPR-A and hPR-B) were stably transfected in Chinese Hamster Ovary (CHO) cells in the presence or absence of the mouse mamma tumor virus (MMTV) promoter and luciferase (LUC) reporter gene. In this way four stably transfected CHO cell lines, i.e. hPR-A, hPR-B, hPR-A-MMTV-LUC and hPR-B-MMTV-LUC cells, were prepared. hPR-A and -B isoforms were compared by binding and transactivation analysis for 14 progestagens and 7 antiprogestagens. Thereby Org 2058 was used as standard in both agonistic and binding assays and Org 31710 in antagonistic assays. The obtained data were compared with relative binding affinities (RBA) for both hPR-A and -B, which are present in human breast tumor MCF-7 cells, and with biopotency estimations with McPhail tests in rabbits and ovulation inhibition and pregnancy interruption tests in rats. The relative binding affinities of 14 progestagens and 7 antiprogestagens towards hPR-A, hPR-B or hPR-A/B of either CHO or MCF-7 cells were highly correlated with respect to ranking. This was also shown by the high correlation coefficients between the RBA's of hPR-B and hPR-A in CHO cells (r = 0.983) and between those of hPR-B of CHO and hPR A/B of MCF-7 cells (r = 0.957). The transactivation data of the 14 progestagens and 7 antiprogestagens for the hPR-B-MMTV-LUC cells were compared with those for hPR-A-MMTV-LUC cells and showed no differences between both cell lines with exception of the progestagens Org 32704 and 33766 and the antiprogestagen Org 33245. Therefore only the relative agonistic activities (RAA) and relative antagonistic activities (RANTA) of hPR-B-MMTV-LUC cells were compared with RBA values of hPR-B, showing a high similarity in ranking for the tested compounds, and high correlation coefficients of r = 0.91 and r = 0.97, respectively. Remarkably, RBA's were 1.6 fold higher than RAA's and RANTA's. These in vitro RBA, RAA and RANTA values for hPR-B were checked for their pharmacological relevance by in vivo biopotency measurements with the 14 progestagens and 7 antiprogestagens in rabbits and rats. The in vitro binding and transactivation potencies of progestagens appeared to be very predictive for in vivo analysis on endometrium proliferation in rabbits in the McPhail test with correlation coefficients of r = 0.81 and r = 0.87, while ovulation inhibition in rats correlated less well with r = 0.516 and r = 0.65. On the other hand, the antiprogestagenic potencies found with binding and transactivation assays had a good correlation with the potencies in the pregnancy interruption test in rats for all antiprogestagens tested, being r = 0.849 and r = 0.744, respectively. In conclusion, the binding and transactivation potencies for the tested compounds in hPR-A and -B containing cell lines showed in general a good resemblance. The transactivation studies with hPR-B-MMTV-LUC cells indicated that ranking of compounds was fairly identical to binding analysis and could be used for pre-screening of the (anti)-progestagenic bioactivity in the McPhail test in rabbits, the ovulation inhibition test and the pregnancy interruption test in rats. Therefore this transactivation assay can replace binding assays. Moreover, direct pre-screening of agonists, antagonists and partial antagonists is even possible in this in vitro bioassay, making transactivation assays for a particular class of chemical compounds to a valuable pre-screening tool for in vivo studies.

Animals↗
PubMed2003

Forensic web watch--medicolegal aspects of paediatric pathology.

The trials over the deaths of Matthew Eappen and Victoria Climbie have highlighted the importance of forensic evidence in cases of suspected child abuse. The debate as to whether bruises, fractures or head injuries have been sustained as a result of previous trauma or non-accidental injury is central to these, and other, cases. A variety of subjects are encountered in forensic paediatric pathology, including Shaken Baby Syndrome, non-accidental injury, retinal haemorrhage, skeletal injury, Sudden Infant Death, sexual abuse and Munchausen Syndrome by Proxy. The coverage of these areas on the internet was assessed using two search engines (Google and the meta-search engine Mamma) and revealed patchy coverage. The majority of sites uncovered were, unsurprisingly, aimed at the layperson concerned by such issues; however, several sites containing useful information for the professional are available.

Journal Article↗
PubMed2004

Heritable aspects of dysplastic breast glandular tissue (DY).

Breast parenchymal patterns, as visible on mammograms, are determined by the relative amount of radio-dense, glandular dysplastic tissue DY). High percentages of DY are related to higher breast cancer risk. Previous studies reported heritable influences on DY of 32-67%, depending on the family relationship that was studied. depending on the family relationship that was studied. We assessed heritability in 466 sister-, 25 dizygotic twin- and 26 monozygotic twin-pairs participating in a population-based breast cancer screening program; the DOM project (Diagnostic Investigation Mamma Carcinoma). The heritability was estimated for non-twin sisters, dizygotic and monozygotic twins seperately by computing correlations between siblings from the dichotomous DY-score (high risk versus low risk). This was done using methods based on the number of shared genes per sibtype. Heritability estimates were 38, 34 and 88% for sisters, dizygotic twins and monozygotic twins respectively. Heritability estimates from models that combine monozygotic twins with dizygotic twins or sisters indicated that combine monozygotic twins with dizygotic twins or sisters indicated that dominant gene effects, genetic interactions or gene-environment effects could be involved. Parity appeared to have an effect on the heritabile influence with estimates ranging from 90% in sisters that were both nulliparous, to 2% in sisterpairs discordant for nulliparity. These result indicate a substantial genetic influence on DY, but with a possible modifying ability of other factors, such as parity.

Adult↗
PubMed2003

Chemical and behavioural characterization of the rabbit mammary pheromone.

Mammals owe part of their evolutionary success to the harmonious exchanges of information, energy and immunity between females and their offspring. This functional reciprocity is vital for the survival and normal development of infants, and for the inclusive fitness of parents. It is best seen in the intense exchanges taking place around the mother's offering of, and the infant's quest for, milk. All mammalian females have evolved behavioural and sensory methods of stimulating and guiding their inexperienced newborns to their mammae, whereas newborns have coevolved means to respond to them efficiently. Among these cues, maternal odours have repeatedly been shown to be involved, but the chemical identity and pheromonal nature of these cues have not been definitively characterized until now. Here we focus on the nature of an odour signal emitted by the female rabbit to which newborn pups respond by attraction and oral grasping, and provide a complete chemical and behavioural description of a pheromone of mammary origin in a mammalian species.

Animals↗
PubMed2000

Scintimammography enhances negative predictive value of non-invasive pre-operative assessment of breast lesions.

AIMS: The aim of this study was to develop a criterion with a high negative predictive value for the evaluation of breast lesions. We aimed to determine the value of combining three non-invasive tests, mammography (MM), ultrasonography (USS) and 99mTc-methoxyisobutylisonitrite (99mTc-MIBI) scintimammography (scinti-MM). METHODS: We included 94 consecutive patients with suspected lesions detected by mammography or on physical examination. MM, USS and scinti-MM were performed no more than 4 weeks prior to excisional biopsy in all patients. We then compared the biopsy results with a score calculated for each patient, derived from the results of the three tests, which we termed 'mamma malignancy index' (MMI). RESULTS: Each of the three exams yielded a score ranging from 0 to 2, with 0 representing an almost certainly benign lesion, 1 an indeterminate finding and 2 a likely malignant lesion, and hence giving a total score ranging from 0 to 6. The biopsy results showed that the lesions in 64 patients were benign. Forty-nine (77%) of these patients had received an MMI score of 0 or 1. The negative predictive value for malignancy in patients with a score less than 2 was 100%. CONCLUSIONS: Since the smallest detected lesion was 9 mm in diameter, we conclude that MMI may be a highly useful diagnostic tool in the delineation of breast lesions > or =1 cm which should not be routinely referred for biopsy but may be followed non-invasively. Although fine needle aspiration has limitations, we would recommend it as a less invasive method to evaluate suspected lesions smaller than 1 cm.

Adult↗
PubMed1979

[Experimental study on image quality when using screens in mammography (author's transl)].

1. Different type of screens and x-ray films have been investigated using a Kodak mamma-phantom I.T.O. 745 and compared with conventional non screen industrial film radiography. 2. Dosisreduction by using screens depends on the used film/screen system. It is possible to reach a relation of 1 : 10. 3. The information depends on type of screen and of type of film. Therefore, it is possible to reach the information of non screen industrial film radiographs. 4. A suitable film/screen system allows without loss of any diagnostic information to replace non screen industrial films needing a high exposure dosis by a film/screen system needing decreases dosis.

Female↗
PubMed1979

[Clinical experience with mammography using grids (author's transl)].

Duplicate examinations were carried out on 122 patients in order to compare the results of mammography using a grid technique (Diagnost U. Müller) with a film-screen systemadn also a conventional set without screens (Mamma-Diagnost, Müller). The results were compared with reference to film quality and dose. The new technique was superior to the conventional method in all respects, independent of the size of the gland. Another advantage of the grid technique was the larger available film size. Dose requirements for grid mammography with a film-screen system was less than for conventional techniques by a factor of about 1.8. The results speak for increased use of the grid technique in clinical practice.

Breast Neoplasms↗
PubMed2005

[Pharmaco-toxicological and clinical studies with colocynth pulp extracts (Extr. colocynthidis fructus)].

Colocynth pulp extract is a long-serving laxative. Contesting the official characterizations "drastic irritant action, no longer defensible" by suitable pharmacotoxicologic studies, extracts of the drug with increasing concentrations of the effective constituant "Cucurbitacins" were prepared in order to define efficacy ranges lethal to rats and mice. The extract Koloquinthentrockenextrakt Alpha with the highest content of Cucurbitacins (23,2 % delta 232,64 mg/g) permitted the definition of the LD50 for female (tentative because of death inhibition under maximal doses) and male rats; the mean LD50 = 281,8 and 525,6 mg/kg extract, respectively, equivalent to 66 and 122 mg/kg Cucurbitacins. This corresponds to 660- to 1220-fold therapeutic doses. Repeated administrations of 10- and 50-fold therapeutic doses to rats for 30 days produced no negative effects. The symptoms of rodent poisoning are described in detail. Pharmacologic doses were not toxic on rat liver slices, did not influence breathing and circulation parameters in guinea pigs (under the maximal dose of 41,6 mg/kg Cucurbitacins, 3/10 animals died of breathing failure) nor the behaviour of mice, nor were they mutagen (Ames test). Colocynth pulp extract weakly inhibited the growth of MDA-MB435 mamma carcinoma cells, but had no influence on the growth of B16 mouse melanoma cells. P388 mouse leukemia cells and L 929 mouse fibroblasts were not significantly influenced. High doses of Colocynth pulp extract inhibited diuresis and electrolyte excretion in rats. The Cucurbitacins E and I were rapidly metabolized in S9-supernatants of rat livers. A dried ethanolic Salvia fruit extract alleviated the toxicity of lethal doses of Colocynth pulp extract when administered simultaneously. A field study with 200 patients and a phase I study with 60 volunteers were conducted in Germany with Colocynth pulp extract from April to October 1998, andfrom December 2002 to March 2003, respectively. Data on the tolerance of the highest allowed dose and of a half-maximal dose administered to volunteers for 14 days in comparison to placebo, as well as data on the efficacy of a treatment course of 3 days of patients with obstipation, were to be gained. Clinical laboratory investigations of volunteers gave no indication of pathological changes even under the highest dose. In patients with obstipation and associated complaints, the administration for 3 days at maximum led to an increased frequency of bowel movements. At the same time, the discomforts accompanying obstipation were significantly relieved. Patients with obstipation defined tolerance as good. Volunteers, on the other hand, judged the tolerance of the drug significantly inferior ("good" - "average") to that of placebo ("very good" - "good"). The low risk potential of Colocynth pulp extract documented in pharmaco-toxicological studies was confirmed during administration to humans.

Animals↗
PubMed2000

[Carcinoma-associated retinopathy: a review with clinical examples].

Cancer-associated retinopathy (CAR) is a rare paraneoplastic syndrome. In this survey we report about two further patients with CAR, who were referred to the University Eye Hospital of Tuebingen within a few months. The most common primary tumor associated with CAR is small cell carcinoma of the lung. Case reports about rhabdomyosarcoma, carcinoma of the endometrium, prostate and mamma were also described. The exact pathogenesis of CAR is still unknown. Specific autoantibodies were found against the photoreceptor protein recovering (23-kd retinal CAR antigen). However, this reaction is not present in all patients, and probably other antigens are also involved. Most of the patients experience symptoms of CAR before the primary tumor is detected. Besides glare sensitivity and flashing lights, a rapidly progressive, often asymmetric visual loss may occur. Although paracentral and mid-peripheral scotomas can be found frequently, visual field defects are often quite heterogeneous. Typically, the responses in the electroretinogram (ERG) are markedly reduced, but normal ERGs were also described. The fundus picture in CAR shows sheathing of the retinal vessels, narrowing of the arterioles and clumbing of the retinal pigment epithelium. The prognosis is poor. Frequently there is progression to bilateral loss of vision within a few months. Treatment of the primary tumor does not seem to alter the ocular prognosis. Systemic corticosteroids may be helpful in some patients. Nevertheless, no proven therapeutic regimen is currently available.

Aged↗