Estrogen receptors and the mammary gland

For several decades it has been known that steroid hormones, estrogen and progesterone, regulate some genes involved in the growth, proliferation and differentiation of the mammary-gland in animals and humans. In the last years, the presence or absence of the nuclear estrogen receptor has been used by clinicians as a marker for tumor malignancy, as a prognostic index or as an important parameter for hormonal therapy with anti-estrogenic compounds of some hormone-dependent breast cancers. This review shows some advances in the knowledge of the structure, function, molecular mechanisms of estrogenic activity, and interaction with proteins like protooncogenes and growth factors. Also, we refer to the role of the estrogen receptor in the physiophatology of breast cancer.     

Peptides generated from milk proteins in the bovine mammary gland during involution

OBJECTIVE: To determine if the interaction between isoniazid and hydralazine, consisting of increased hypotension accompanied by bradycardia, occurs with other vasodilators. METHODS: Blood pressure and heart rate responses to a number of vasodilators were determined in rats under chloralose-urethane, pretreated or not with 250 mg/kg of isoniazid. The influence of this dose of isoniazid on GABA levels in the hypothalamus and pons-medulla was assessed in other groups of rats. RESULTS: Increased hypotension and bradycardia following i.p. isoniazid were observed with dipyridamole, prazosin, pinacidil and hydralazine given i.v. Bradycardia without increased hypotension appeared with papaverine and verapamil, while increased hypotension with unchanged heart rate was observed with minoxidil and captopril. Isoniazid decreased GABA in the hypothalamus and pons-medulla. CONCLUSIONS: At the high dose used, isoniazid interacts with various vasodilators, irrespective of their mechanism of action. The interaction could be due to the influence of the drug on GABA levels at cardiovascular regulatory sites.     

Parathyroid hormone-related protein: a regulated calcium-mobilizing product of the mammary gland

Parathyroid hormone-related protein shares similarities in sequence and function with the endocrine hormone, parathyroid hormone. However, unlike parathyroid hormone, a product of the parathyroid glands, parathyroid hormone-related protein has a wide distribution in tissues, including the mammary gland. Although during pregnancy the expression of parathyroid hormone-related protein in the mammary gland is low, following birth, protein levels rise sharply in the gland in response to elevations in serum prolactin. Large amounts of parathyroid hormone-related protein are secreted into milk, suggesting a possible role in the neonate. Transient phosphaturia and elevations of parathyroid hormone-related protein in mammary vein plasma support a possible endocrine function for parathyroid hormone-related protein during lactation. Recent evidence suggests a local function for parathyroid hormone-related protein in the lactating mammary gland, and evidence exists that parathyroid hormone-related protein stimulates calcium secretion by the goat mammary gland. Parathyroid hormone-related protein, a putative vasodilator, is produced by the external nutrient vasculature of the mammary gland, and levels within this tissue are regulated during lactation. Infusion of parathyroid hormone-related protein into the ovine mammary artery increases gland blood flow, suggesting a role for the protein in modulation of mammary gland hemodynamics. Regulation of parathyroid hormone-related protein synthesis by the lactating gland, together with the protein's actions on regional blood flow and calcium secretion, support an important function in the mammary gland during lactogenesis.     

Molecular cloning of the bile salt-dependent lipase of ferret lactating mammary gland: an overview of functional residues

A number of key trends are emerging in long-term care related to financing, new models of service delivery, and shifts in consumer expectations and preferences. Taken together, changes occurring in these areas point to a rapidly transforming long-term care landscape. Financing responsibility is shifting away from the federal government to states, individuals, and their families; providers are integrating and managing acute and long-term care services and adding new services to the continuum of care; and consumers are thinking more seriously about how to plan and pay for their future care needs, as well as how to independently navigate the long-term care system.     

Lymphocyte subpopulations in the mammary gland of the goat

Mammary glands of pregnant, lactating and resting goats were studied by immunohistochemistry for lymphocyte subpopulations using a panel of monoclonal antibodies. All T lymphocyte subpopulations that may have a role in the immune response, CD2+, CD4+, CD8+ and gamma delta T cells and subsets, were present in the mammary gland and were noted to increase in number progressively during pregnancy, decrease significantly during lactation, and then moderately increase during the resting period. CD4+ cells, the predominant cell type in the mammary gland, were located mainly in the connective tissue, whereas CD2+, CD8+ and TcR1-N24+ cells were predominant in the intraepithelial areas. TcR1-N6+ cells were detected almost exclusively during pregnancy, being localized mainly in the connective tissue. Their proportion decreased markedly following parturition. Very few WC1-N3+ and -N4+ cells were detected in the mammary gland. It is suggested that the majority of gamma delta T lymphocytes in the mammary gland of the goat are CD2+ CD8+ WCl-, a distinctive subset from that of the WCl+ subset in peripheral blood.     

Environmental streptococcal intramammary infections of the bovine mammary gland

Characteristics of environmental streptococcal IMI were investigated over a 7-yr period for a herd in total confinement. A total of 374 new environmental streptococcal IMI was detected. Approximately 50.5% of IMI were new in the dry period, and 49.5% were new in lactation. The rate of new IMI was .00312 IMI/cow day during the dry period and .00054 IMI/cow day during lactation. The percentages of cows and quarters with an environmental streptococcal IMI present at calving were 10.6 and 3.2%, respectively. The percentage of heifers with an environmental streptococcal IMI at calving was similar to that for cows. The rate of new environmental streptococcal IMI was greater during the 1st mo of lactation than during the remainder of lactation. The rate of IMI during late lactation was higher for older cows than for either heifers or cows in second lactation. The rate of environmental streptococcal IMI during the dry period and during lactation was greatest during summer. The mean days of lactation that cows were infected for all IMI was 12.3 d. Approximately 41% of IMI had a duration of < 8 d. Stage of lactation, season of the year, and parity influenced the rate of new IMI.     

Kinetics of a micelle specific palmitoyltransferase isoenzyme of rabbit mammary gland

Palmityl-CoA: monopalmityl-sn-glycerol 3-phosphate palmitoyltransferase [EC 2.3.1. -] in rabbit mammary gland microsomes is composed of two isoenzymic species. The alpha form (LPAT-alpha) is active with monomeric substrates and inhibited by micelles while the beta form (LPAT-beta) is active only with micelles. By combining the effects of time, temperature, and Tween 80 which selectively inhibited LPAT-alpha, the substrate saturation curve for the LPAT-beta isoenzyme has been successfully determined. Both theoretical and experimental curves are in good agreement.     

Contemporary methods of the target puncture of the mammary gland

New accurate methods of puncture of the mammary gland, making use of preliminary layout using roentgenograms, coordination nets, Cytoguide comprter device, and ultrasound-monitored spot biopsy replaced the traditional poorly informative methods. Sonography-monitored puncture is the most informative in cases with both palpated and unpalpated formations shaped as nodules: it permits imaging in 85% of cases. However, in 25-30% of cases unpalpated cancer presents as microcalcinates and cord-like restructuring which cannot be imaged on sonograms. Moreover, unpalpated cancer presenting as a nodule against the background of fatty involution also may be undiscernible on sonograms. In such cases puncture controlled by roentgenography with a computer device and a relevant kit of disposable instruments is advisable, giving accurate information in 61.1% of cases.     

Molecular weight and subunit size of fatty acid synthetase from rabbit mammary gland

Fatty acid synthetase purified from the mammary gland of the rabbit has a mol. wt. of 968000 as determined by gel filtration. The enzyme gave one band, corresponding to a mol.wt. of approx. 35000, on polyacrylamide-gel electrophoresis in the presence of sodium dodecyl sulphate and phenylmethanesulphonyl fluoride.     

Telomerase activity in the normal and neoplastic rat mammary gland

The 1-methyl-1-nitrosourea-induced rat mammary tumor model system is well studied, reproducible, and widely used. We have investigated whether these tumors possess higher telomerase activity than normal mammary tissue. Using the telomeric repeat amplification protocol assay, we found significantly higher telomerase activity in 36 mammary carcinomas than in 72 mammary glands of virgin rats. The level of telomerase activity in virgin rats was unaffected by strain, age, stage of the estrous cycle, or ovariectomy. However, mammary glands obtained from pregnant rats exhibited telomerase activity comparable to that found in the tumors, possibly reflecting the high epithelial content of these tissues. Indeed, isolated epithelial cells from virgin and pregnant mammary glands and from carcinomas had similar telomerase activities. Thus, telomerase activity is constitutive in the rat mammary epithelium and is not a unique characteristic of malignant transformation in this tissue. These results underscore the importance of attributing biochemical properties to specific cell types in a tissue, a situation not paralleled in the interpretation of data from in vitro models.     

Nerve and vessel supplying ligamentous suspension of the mammary gland

Anatomical findings from 28 breast specimens of female corpses have shown a thin horizontal fibrous septum, originating from the pectoral fascia along the level of the fifth rib, heading toward the nipple. This fibrous septum lies in between a cranial and a caudal vascular network, and being mesentery-like, it is responsible for the supply of the nipple areola complex. The cranial vascular sheet is supplied by the thoracoacromial artery and a branch of the lateral thoracic artery, whereas the caudal sheet is supplied by perforating branches from anastomoses of intercostal arteries. The fibrous septum is also a guiding structure for the main supplying nerve of the nipple. At its borders the septum curves upward into a vertical medial and lateral ligament, which attach the breast to the sternum and the lateral edge of pectoralis minor. These ligaments also contain a regular nerve and vascular supply. In their total, the fibrous septum and its ligaments form a sling of dense connective tissue that acts as a brassiere-like suspensory system. These two structures, the fibrous sling and the vascular and nervous membranes attached to it, are consistent anatomical findings, which have not been described before. Their knowledge could be of value and relevance in clinical application.     

Human gamma-interferon expression in the mammary gland of transgenic mice

Transgenic mice carrying a hybrid gene consisting of ovine beta-lactoglobulin gene sequences and human gamma-interferon (hIFN-g) cDNA were produced. hIFN-g expression in the mammary gland of two lactating transgenic founder females was found. The concentration of active hIFN-g in the milk was estimated as being ca. 1800 IU/ml. The hIFN-g ability to express in the mammary gland was found in the progeny of transgenic founder male.     

First experiences with a new infrared thermometry device in mammary gland diagnosis

A parasitology survey was conducted in five villages in North Sumatra, Indonesia. A total of 3,207 blood smears, 2,066 stool specimens and 969 sera were examined. Sixty (1.9%) inhabitants had malaria (Plasmodium vivax 41, P. falciparum 19), and 20 had Brugia malayi microfilaraemia. The most common intestinal helminths were Trichuris trichiura (87%), Ascaris lumbricoides (75%) and hookworm (58%). Other helminths found in low numbers were Enterobius vermicularis, Strongyloides stercoralis, Taenia sp., Fasciolid, Dicrocoeliid and Echinostoma sp. eggs. Entamoeba coli (25%) was the most common intestinal protozoa followed by Endolimax nana (8%), Entamoeba histolytica (7%), Giardia lamblia (6%), Iodamoeba bütschlii (5%), Entamoeba hartmanni (1%) and Chilomastix mesnili (1%). The amoeba prevalence rate was 31 per cent. Testing of sera for Entamoeba histolytica and Toxoplasma gondii antibodies by the indirect haemagglutination test demonstrated positive reactors in 13 per cent and nine per cent of the population respectively. The greatest number of seropositives for Toxoplasma gondii was at elevations of sea level to five meters and the lowest number at elevations of 5OO-1,000 meters.     

B and T cells are required for mouse mammary tumor virus spread within the mammary gland

Mouse mammary tumor virus (MMTV) is an infectious retrovirus transmitted through milk from mother to newborns. MMTV encodes a superantigen (SAg) whose activity is indispensable for the virus life cycle, since a genetically engineered virus with a mutation in the sag gene neither amplified in cells of the immune system of suckling pups nor infected their mammary glands. When wild-type MMTV was injected directly into the mammary glands of uninfected pubescent mice, their lymphoid as well as mammary gland cells became virus infected. To test whether this infection of lymphoid cells was dependent on SAg activity and required for virus spread within the mammary gland, we performed mammary gland injections of wild-type MMTV(C3H) into two strains of transgenic mice that lacked SAg-cognate, V beta 14+ T cells. Neither the MTV-ORF or LEL strains showed infection of their mammary glands. Moreover, no MMTV infection of their peripheral lymphocytes was detected. Similar experiments with mice lacking B cells (mu-chain knockouts) showed no detectable virus spread in the mammary glands or lymphoid tissues. These data suggest that SAg activity and MMTV-infected lymphocytes are required, not only for initial steps of viral infection, but also for virus spread within the mammary gland. Virus spread at late times in infection determines whether MMTV induces mammary tumors.     

Allogeneic cell therapy for a murine mammary carcinoma

The effect of allogeneic cell therapy on tumor growth was studied in a murine model of mammary carcinoma (4T1) as an experimental model of solid tumors in humans. i.v. inoculation of 4T1 (H-2d) cells into syngeneic mice [BALB/c or (BALB/cXC57BL/6)F1] (F1) carrying the H-2d histocompatible antigens results in tumor colonies in the lungs that finally cause the death of all of the mice. Sublethally irradiated F1 mice were inoculated with 4T1 cells to simulate minimal residual disease and with immunocompetent splenocytes derived from naive donors of F1 (syngeneic), BALB/c (syngeneic to the tumor but semiallogeneic to the host), or C57BL/6 (allogeneic to the tumor and semiallogeneic to the host) mice. The survival of F1 tumor-bearing mice that were treated with allogeneic C57BL/6 splenocytes was significantly prolonged (P < 0.02) compared with hosts given F1 or BALB/c-derived splenocytes that are syngeneic to 4T1 tumor cells. Adoptive transfer of lung cells that were isolated from F1 primary mice inoculated with 4T1 cells and syngeneic BALB/c or F1 splenocytes led to local tumor growth and death in secondary recipients. In contrast, only 1 of 22 secondary recipients developed tumors when inoculated with lung cells derived from F1 mice given allogeneic C57BL/6 splenocytes. All of the 21 secondary hosts survived disease-free for a follow-up time of >200 days. These results indicate that immunocompetent cells allogeneic to the mammary carcinoma cells were able to inhibit tumor development in the primary hosts and to prevent tumor growth in the adoptive recipients, which suggests that allogeneic cell therapy may be an efficient antitumor tool to eradicate minimal residual disease in human solid tumors.     

Bradykinin and functional vasodilatation in the salivary gland

The relationships between left ventricular function and myocardial O2 availability and metabolism were studied in cats with hemorrhagic shock (AP=30 mm. Hg) with the use of a right heart bypass preparation. Aortic flow and heart rate were held constant. Oxygen-carrying capacity was reduced by diluting donor blood with an equal volume of 5 per cent glucose in saline. Oxygen availability was estimated as the product of arterial O2 content and coronary blood flow. All shock animals showed a progressive metabolic acidemia with time, and a fall in coronary flow concomitantly. Four control animals (AP=75 mm. Hg) as well as two shock animals with high arterial oxygen content and hematocrit showed no significant changes in myocardial O2 metabolism or performance over a period of 90 minutes. Nine shock animals with reduced hematocrit demonstrated a progressive reduction in ventricular function, myocardial O2 metabolism, and O2 availability. As O2 availability fell below 10 ml. per minute per 100 Gm. of heart weight, cardiac failure uniformly appeared and was accompanied by a reduction in O2 extraction and consumption. The correlation between left ventricular dP/dt max and O2 availability was highly significant (r = 0.75, p less than 0.01) in shock animals but not in controls. Thus a close relationship between myocardial O2 metabolism and function during the course of hemorrhagic shock has been demonstrated. Reduced myocardial O2 availability is directly linked with the appearance of cardiac failure.